Radiotherapy as nose preservation treatment strategy for cancer of the nasal vestibule:the Dutch experience

Contains fulltext : 238459.pdf (Publisher’s version ) (Open Access

Metabolic markers in relation to hypoxia; staining patterns and colocalization of pimonidazole, HIF-1α, CAIX, LDH-5, GLUT-1, MCT1 and MCT4

Contains fulltext : 96097.pdf (postprint version ) (Open Access)BACKGROUND: The cellular response of malignant tumors to hypoxia is diverse. Several important endogenous metabolic markers are upregulated under hypoxic conditions. We examined the staining patterns and co-expression of HIF-1alpha, CAIX, LDH-5, GLUT-1, MCT1 and MCT4 with the exogenous hypoxic cell marker pimonidazole and the association of marker expression with clinicopathological characteristics. METHODS: 20 biopsies of advanced head and neck carcinomas were immunohistochemically stained and analyzed. All patients were given the hypoxia marker pimonidazole intravenously 2 h prior to biopsy taking. The tumor area positive for each marker, the colocalization of the different markers and the distribution of the markers in relation to the blood vessels were assessed by semiautomatic quantitative analysis. RESULTS: MCT1 staining was present in hypoxic (pimonidazole stained) as well as non-hypoxic areas in almost equal amounts. MCT1 expression showed a significant overall correlation (r = 0.75, p < 0.001) and strong spatial relationship with CAIX. LDH-5 showed the strongest correlation with pimonidazole (r = 0.66, p = 0.002). MCT4 and GLUT-1 demonstrated a typical diffusion-limited hypoxic pattern and showed a high degree of colocalization. Both MCT4 and CAIX showed a higher expression in the primary tumor in node positive patients (p = 0.09 both). CONCLUSIONS: Colocalization and staining patterns of metabolic and hypoxia-related proteins provides valuable additional information over single protein analyses and can improve the understanding of their functions and environmental influences

Decreased 3D observer variation with matched CT-MRI, for target delineation in Nasopharynx cancer

Contains fulltext : 88137.pdf (publisher's version ) (Open Access)PURPOSE: To determine the variation in target delineation of nasopharyngeal carcinoma and the impact of measures to minimize this variation. MATERIALS AND METHODS: For ten nasopharyngeal cancer patients, ten observers each delineated the Clinical Target Volume (CTV) and the CTV elective. After 3D analysis of the delineated volumes, a second delineation was performed. This implied improved delineation instructions, a combined delineation on CT and co-registered MRI, forced use of sagittal reconstructions, and an on-line anatomical atlas. RESULTS: Both for the CTV and the CTV elective delineations, the 3D SD decreased from Phase 1 to Phase 2, from 4.4 to 3.3 mm for the CTV and from 5.9 to 4.9 mm for the elective. There was an increase agreement, where the observers intended to delineate the same structure, from 36 to 64 surface % (p = 0.003) for the CTV and from 17 to 59% (p = 0.004) for the elective. The largest variations were at the caudal border of the delineations but these were smaller when an observer utilized the sagittal window. Hence, the use of sagittal side windows was enforced in the second phase and resulted in a decreased standard deviation for this area from 7.7 to 3.3 mm (p = 0.001) for the CTV and 7.9 to 5.6 mm (p = 0.03) for the CTV elective. DISCUSSION: Attempts to decrease the variation need to be tailored to the specific causes of the variation. Use of delineation instructions multimodality imaging, the use of sagittal windows and an on-line atlas result in a higher agreement on the intended target

Evidence that involucrin, a marker for differentiation, is oxygen regulated in human squamous cell carcinomas

Hypoxia is associated with poor prognosis in squamous cell carcinomas affecting both local control and distant spread (Hockel et al., 1996a, 1996b, 1999; Nordsmark et al, 1996; Fyles et al, 2002; Kaanders et al, 2002). Local control is believed to depend on local radiation response while distant spread is thought to depend, at least in part, on the induction of oxygen-regulated proteins. In order to test this, pimonidazole, an extrinsic marker for tissue hypoxia (Arteel et al, 1995; Kennedy et al, 1997; Varia et al, 1998; Raleigh et al, 1999), with prognostic value (Kaanders et al, 2002) was used to examine whether ORPs such as VEGF (Raleigh et al, 1998a), metallothionein (Raleigh et al, 2000), HIF-1α (Janssen et al, 2002), Glut-1 (Airley et al, 2003) and CAIX (Olive et al, 2001) were, in fact, associated with cellular hypoxia in human tumours. Unexpectedly, VEGF and metallothionein (MT) were not expressed in the majority of hypoxic cells in squamous cell carcinomas (Raleigh et al, 1998a, 2000) even though these ORPs were induced by hypoxia in experimental systems (Shweiki et al, 1992; Raleigh et al, 1998b; Murphy et al, 1999)

Patient reported toxicity and quality of life after hypofractionated high-dose intensity-modulated radiotherapy for intermediate- and high risk prostate cancer

Background and purpose: For irradiation of localized prostate-cancer, moderately-hypofractionated regimens with a variety of dose per fraction are used. We adopted a regimen of 70 Gy in 28 fractions of 2.5 Gy, using state of the art radiotherapy (RT) and closely monitored the efficacy, toxicity and health-related quality of life (HRQoL) in a large cohort, using patient-reported outcomes. Materials and methods: Between 2008 and 2016, 462 patients with intermediate- to high-risk localized prostate cancer were treated with RT, 28 fractions of 2.5 Gy, using IMRT/VMAT, an online fiducial-maker based correction protocol and a daily inserted endorectal balloon. Overall freedom from failure (no biochemical or clinical recurrence) , as well as self-reported genitourinary (GU) and gastrointestinal (GI) related toxicity and HRQoL are reported. Results: Overall freedom from failure rates at 3 and 5 years were 92.0% (89.1–94.9%) and 83.5% (78.6–88.4%), respectively. Prevalence rates of grade ≥ 2 GU/GI-toxicity were 16.3%/6.3% and 22,1%/3.2% after 3 and 5 years respectively. The 5-year actuarial incidences of grade ≥ 2 GU/GI-toxicity were 43.5%/18.5%. HRQoL worsened during RT and gradually recovered thereafter, In accordance with the prevalence rates. Conclusion: Treatment of intermediate- or high-risk localized prostate cancer with RT to 70 Gy in 28 fractions with IMRT/VMAT, using fiducial markers and an endorectal balloon leads to good long-term tumor control rates and acceptable patient reported toxicity rates. Furthermore, patient-reported outcomes, including HRQoL, are essential for a good comparison between different studies. Finally, prevalence rates show a better correlation with HRQoL than actuarial incidence rates do and might therefore better represent the burden of toxicity

alphaB-crystallin stimulates VEGF secretion and tumor cell migration and correlates with enhanced distant metastasis in head and neck squamous cell carcinoma

Contains fulltext : 111464.pdf (publisher's version ) (Open Access