Role of Mobility Strategy in moderating the effect Of ERP performance to operational performance: (Study in Indonesian palm oil plantation industries)

Introduction: Inter-observer variability (IOV) in target volume delineation is a well-documented source of geometric uncertainty in radiotherapy. Such variability has not yet been explored in the context of adaptive re-delineation based on imaging data acquired during treatment. We compared IOV in the pre- and mid-treatment setting using expert primary gross tumour volume (GTV) and clinical target volume (CTV) delineations in locoregionally advanced head-and-neck squamous cell carcinoma (HNSCC) and (non-)small cell lung cancer [(N)SCLC]. Material and methods: Five and six observers participated in the HNSCC and (N)SCLC arm, respectively, and provided delineations for five cases each. Imaging data consisted of CT studies partly complemented by FDG-PET and was provided in two separate phases for pre- and mid-treatment. Global delineation compatibility was assessed with a volume overlap metric (the Generalised Conformity Index), while local extremes of IOV were identified through the standard deviation of surface distances from observer delineations to a median consensus delineation. Details of delineation procedures, in particular, GTV to CTV expansion and adaptation strategies, were collected through a questionnaire. Results: Volume overlap analysis revealed a worsening of IOV in all but one case per disease site, which failed to reach significance in this small sample (p-value range .063-.125). Changes in agreement were propagated from GTV to CTV delineations, but correlation could not be formally demonstrated. Surface distance based analysis identified longitudinal target extent as a pervasive source of disagreement for HNSCC. High variability in (N)SCLC was often associated with tumours abutting consolidated lung tissue or potentially invading the mediastinum. Adaptation practices were variable between observers with fewer than half stating that they consistently adapted pre-treatment delineations during treatment. Conclusion: IOV in target volume delineation increases during treatment, where a disparity in institutional adaptation practices adds to the conventional causes of IOV. Consensus guidelines are urgently needed

Retrospective investigation of the prognostic value of the β1 integrin expression in patients with head and neck squamous cell carcinoma receiving primary radio(chemo)therapy.

This retrospective study evaluated the expression of β1 integrins and associated proteins as prognostic markers for primary radio(chemo)therapy outcome of patients with locally advanced head and neck squamous cell carcinomas (HNSCC). Tissue microarrays were prepared from 224 HNSCC patients undergoing curative primary radio(chemo)therapy from 1996 to 2005. Staining intensities of β1 integrin and its downstream-proteins FAK, phosphorylated FAK as well as the β1 integrin ECM ligands fibronectin and collagen type-I were determined. Their association to the primary endpoint loco-regional control and the secondary endpoints overall survival and freedom from distant metastasis was analyzed by Cox regression. None of the considered molecular parameters showed a significant association with loco-regional control and freedom from distant metastasis. Patients with p16 positive tumors or tumors with a low intensity of fibronectin showed significantly higher overall survival in univariable regression. In multivariable regression including additional clinical parameters, however, these parameters were not significantly associated with overall survival. Our study in a HNSCC patient cohort treated with primary radio(chemo)therapy does not reveal a prognostic value of β1 integrin expression

Sites of recurrent disease and prognostic factors in SCLC patients treated with radiochemotherapy

Objectives: Concurrent radiochemotherapy (RCHT) is standard treatment in locally advanced small cell lung cancer (SCLC) patients. Due to conflicting results on elective nodal irradiation (ENI) or selective node irradiation (SNI) there is no clear evidence on optimal target volumes. Therefore, the purposes of this study were to assess the sites of recurrent disease in SCLC and to evaluate the feasibility of SNI versus ENI. Methods: A retrospective single-institution study of 43 consecutive patients treated with RCHT was performed. After state-of-the-art staging including FDG-PET/CT, all patients underwent three-dimensional conformal radiotherapy to a total dose of 45â¯Gy in twice-daily fractions of 1.5â¯Gy starting concurrently with the first or second chemotherapy cycle. All sites of loco-regional recurrences were correlated to the initial tumor and dose delivered. The impact of potential prognostic variables on outcome was evaluated using the Cox-regression model. Results: 13 patients (30%) relapsed locally or regionally: six within the initial primary tumor volume, five within the initially affected lymph nodes, one metachronously within primary tumor and initially affected lymph nodes, and one both inside and outside of the initial nodal disease. All sites of loco-regional recurrence had received 92â106% of the prescribed dose. Conclusion: In our study most recurrences occurred within the primary tumor or initially affected lymph nodes, or distantly. We did not register any case of isolated nodal failure, supporting the use of selective nodal irradiation, possibly with the addition of supraclavicular irradiation in patients with nodal disease in the upper mediastinum. Keywords: Small cell lung cancer, Recurrence, Radiotherapy, Selective node irradiatio

Independent validation of the prognostic value of cancer stem cell marker expression and hypoxia-induced gene expression for patients with locally advanced HNSCC after postoperative radiotherapy

Objective: To validate the impact of HPV status, cancer stem cell (CSC) marker expression and tumour hypoxia status in patients with locally advanced head and neck squamous cell carcinoma (HNSCC), who received postoperative radiotherapy. The results of the exploration cohort have previously been reported by the German Cancer Consortium Radiation Oncology Group (DKTK-ROG; Lohaus et al., 2014; Linge et al., 2016). Materials and methods: For 152 patients with locally advanced HNSCC the impact of HPV16 DNA status, CSC marker expression and hypoxia-associated gene signatures on outcome of postoperative radiotherapy were retrospectively analysed. Out of them, 40 patients received postoperative radiochemotherapy. Cox models presented in a previous study were validated using the concordance index as a performance measure. The primary endpoint of this study was loco-regional control. Results were compared to those previously reported by DKTK-ROG. Results: Loco-regional control, freedom from distant metastases and overall survival were inferior to the previously reported cohort. Despite of this, the prognostic value of the combination of HPV infection status, CSC marker expression (SLC3A2) and tumour hypoxia status could be validated in univariate analyses using an independent validation cohort. For multivariate models, the concordance index was between 0.58 and 0.69 in validation, indicating a good prognostic performance of the models. The inclusion of CD44 and the 15-gene hypoxia signature moderately improved the performance compared to a baseline model without CSC markers or hypoxia classifiers. Conclusions: The HPV status, CSC marker expression of CD44 and SLC3A2 as well as hypoxia status are potential prognostic biomarkers for patients with locally advanced HNSCC treated by postoperative radiotherapy

Exploratory prospective trial of hypoxia-specific PET imaging during radiochemotherapy in patients with locally advanced head-and-neck cancer

AbstractPurposeTo explore in a prospective trial the prognostic value of hypoxia imaging before and during radiochemotherapy in patients with locally advanced head and neck cancer.Patients and methodsTwenty-five patients with stage III/IV head and neck cancer were investigated with [18F]-fluoromisonidazole (FMISO) PET/CT at four time points during radiochemotherapy (baseline, 8–10Gy, 18–20Gy,50–60Gy). FMISO PET/CT image parameters were extracted including maximum-tumour-to-background (TBRmax) and thresholded volume at different TBR ratios. CT volume and baseline FDG-PET/CT image parameters were also included. Parameters at all time points were investigated for their prognostic value with the local-progression-free-survival endpoint (LPFS). Significance was evaluated with multivariate Cox (including clinical parameters) and Log-rank tests.ResultsFMISO-image parameters were found to have a strong association with the LPFS endpoint, and were strongest at the week 1 and 2 time points (p=0.023–0.048 and 0.042–0.061 respectively on multivariate Cox). Parameters measured at baseline were only significant on univariate analysis. None of the clinical parameters, and also FDG- or CT-delineated volumes, were significantly associated with LPFS.ConclusionThis prospective, exploratory study demonstrated that FMISO-PET/CT imaging during the initial phase of treatment carries strong prognostic value. FMISO-PET/CT imaging at 1 or 2weeks during treatment could be promising way to select patients that would benefit from hypoxia modification or dose-escalated treatment. A validation study is on-going