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Introduction: Radiation plays a major role in treatment of locoregional control of Head and Neck Squamous cell carcinoma (HNSCC). Anaemia is considered a contributor to intra-tumour hypoxia and tumour resistance to ionizing radiation and most evidences are from developed world, we prospectively investigated the exact role of anaemia in treatment outcome of Stage III/IVA HNSCC in our patient population. Aim of the Study: Primary end point: To analyse the Pre- Radiotherapy haemoglobin level and early response of treatment in stage III/IVA HNSCC and to determine the relationship of Pre-Radiotherapy haemoglobin level with other prognostic factors. Materials and Methods: This non-interventional single blinded randomized study enrolled patients attending the OPD consecutively, who met our eligibility criteria. Inclusion Criteria: HNSCC patients of Stage III/IVA aged ≥18 years and ≤ 70 years with ECOG status of 1or 2 and willing for concurrent chemoradiation and at least 6 weeks of follow up. Exclusion Criteria: 1) Previous history of treatment for malignancy or radiation in head and neck site. 2) Patients with other fatal and non-fatal pre-morbid or co-morbid conditions that can affect the outcome or the overall survival. Patients with Pre-radiotherapy haemoglobin status < 10 g/dl were given haematinic support and/or blood transfusion. All patients received concurrent chemotherapy (weekly cisplatin) and radiation in conventionally fractionated dose of 66Gy. Early treatment responses were evaluated with Revised RECIST version 1.1 and Data analysis using SPSS version 17.0. Results: Ninety one patients enrolled had mean age of 55.63 (range: 32-69), a median of 56 and mode of 60. Seventy one were males (78%) and 20 females (22%) with a performance status of ECOG 1 in 43 (47%) patients and ECOG 2 in 48 (53%); Pre-RT Hb level of <10.7 g/dl in 38 (42%) patients and ≥10.7 in 53 (58%) patients; Pre-RT Hb level was <12 g/dl in 67 (74%) patients and ≥12 in 24 (26%) patients. Tumour sites were - Nasopharynx 7 (8 %), Oral Cavity 18 (20 %), Oropharynx 32 (35 %), Hypopharynx 23 (25 %) and Larynx 11 (12 %). Twenty five (27%) had Grade 2 mucositis and 66 (73%) had Grade 3 mucositis. Fifty eight (64%) patients completed treatment with NO breaks and 33 (36%) with treatment breaks for ≥5 days. Pre-radiotherapy haemoglobin ≥ 10.7 g/dl (p < 0.001), ECOG performance status (p = 0.0002), Treatment interruptions for > 5 days (p = <0.0001), Mucositis reaction (p = <0.0001) showed statistical significance with outcome of response. Conclusion: The study found that performance status, pre-RT haemoglobin level, radiotherapy interruptions > 5 days and nondevelopment of grade III mucositis was found to be significantly associated with good loco-regional control. Haemoglobin level ≥10.7 g/dl was associated with better treatment outcome, higher performance status, fewer treatment interruptions and lesser degree of mucositis. Transfusion did not affect the outcome. Definitive conclusions and recommendations need further expansion of our study for better statistical power. [ABSTRACT FROM AUTHOR]

Purpose: Hyperthermic isolated limb perfusion (ILP) with recombinant tumour necrosis factor alpha (TNF) and melphalan contributes to limb-saving treatment in patients with locally advanced extremity soft tissue sarcoma (STS). This study was conducted to evaluate the dynamic changes of tumour oxygenation and temperature during ILP and their effects on treatment response. Patients and methods: Tumour oxygenation (pO2) and tumour temperature were measured by intratumourally placed O2-sensitive catheter electrodes in 34 patients who underwent ILP for locally advanced or recurrent STS. Tumour response to ILP was assessed by the fraction of tumour necrosis in the resection specimen. Results: Mean tumour pO2 prior to application of TNF and melphalan was 36 mm Hg (range: 2-116 mm Hg) and dropped significantly to 13 mm Hg (range: 0-67 mm Hg, p = 0.03) during ILP. Mean tumour tissue temperature increased from 34.4°C (range 32.4-36.4) to 38.5°C (range 34.1-40.4, p = 0.0001). The mean fraction of necrosis in the resection specimen was 65% (range 5-99). Only the tumour tissue temperature at the onset of ILP correlated with the extent of tumour necrosis ( p = 0.01). Conclusion: ILP with TNF and melphalan induces severe oxygen deprivation in soft tissue sarcoma. However, changes in tumour oxygenation did not correlate with treatment response. [ABSTRACT FROM AUTHOR]

Tumour blood flow before and during clinically relevant mild hyperthermia exhibits pronounced heterogeneity. Flow changes upon heating are not predictable and are both spatially and temporally highly variable. Flow increases may result in improved heat dissipation to the extent that therapeutically relevant tissue temperatures may not be achieved. This holds especially true for tumours or tumour regions in which flow rates are substantially higher than in the surrounding normal tissues. Changes in tumour oxygenation tend to reflect alterations in blood flow upon hyperthermia. An initial improvement in the oxygenation status, followed by a return to baseline levels (or even a drop to below baseline at high thermal doses) has been reported for some tumours, whereas a predictable and universal occurrence of sustained increases in O2 tensions upon mild hyperthermia is questionable and still needs to be verified in the clinical setting. Clarification of the pathogenetic mechanisms behind possible sustained increases is mandatory. High-dose hyperthermia leads to a decrease in the extracellular and intracellular pH and a deterioration of the energy status, both of which are known to be parameters capable of acting as direct sensitisers and thus pivotal factors in hyperthermia treatment. The role of the tumour microcirculatory function, hypoxia, acidosis and energy status is complex and is further complicated by a pronounced heterogeneity. These latter aspects require additional critical evaluation in clinically relevant tumour models in order for their impact on the response to heat to be clarified. [ABSTRACT FROM AUTHOR]

Introduction. Tumour hypoxia is an important factor that confers radioresistance to the affected cells and could thus decrease the tumour response to radiotherapy. The development of advanced imaging methods that quantify both the extent and the spatial distribution of the hypoxic regions has created the premises to devise therapies that target the hypoxic regions in the tumour. Materials and methods. The present study proposes an original method to prescribe objectively dose distributions that focus the radiation dose to the radioresistant tumour regions and could therefore spare adjacent normal tissues. The effectiveness of the method was tested for clinically relevant simulations of tumour hypoxia that take into consideration dynamics and heterogeneity of oxygenation. Results and discussion. The results have shown that highly heterogeneous dose distributions may lead to significant improvements of the outcome only for static oxygenations. In contrast, the proposed method that involves the segmentation of the dose distributions and the optimisation of the dose prescribed to each segment to account for local heterogeneity may lead to significantly improved local control for clinically-relevant patterns of oxygenation. The clinical applicability of the method is warranted by its relatively easy adaptation to functional imaging of tumour hypoxia obtained with markers with known uptake properties. [ABSTRACT FROM AUTHOR]

Darbepoetin alfa (Aranesp), Amgen) is a novel erythropoiesis-stimulating protein with a serum half-life longer than recombinant human erythropoietin (Epo), used in the treatment of cancer-associated anaemia. Anaemia is known to adversely affect prognosis and response to treatment in cancer patients. Solid tumours contain regions of hypoxia due to poor vascular supply and cellular compaction. Although hypoxic stress usually results in cell death, hypoxia-resistant tumour cells are genetically unstable and often acquire a drug-resistant phenotype. Increasing tumour oxygenation and perfusion during treatment could have the doubly beneficial outcome of reducing the fraction of treatment-resistant cells, while increasing drug delivery to previously hypoxic tissue. In this study, we examined the effect of darbepoetin alfa on chemotherapy sensitivity and delivery in an in vivo model of Lewis lung carcinoma, shown here to express the Epo receptor (EpoR). We identified that weekly darbepoetin alfa treatment, commencing 10 days before chemotherapy, resulted in a significant reduction in tumour volume compared to chemotherapy alone. This was mediated by the prevention of anaemia, a reduction in tumour hypoxia and a concomitant increase in drug delivery. Darbepoetin alfa treatment alone did not modulate the growth of the EpoR-expressing tumour cells. This study identifies an important role for darbepoetin alfa in increasing the therapeutic index of chemotherapy. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the feasibility of functional MR imaging (fMRI) at 1.5 T, exploiting blood oxygenation level-dependent (BOLD) contrast, for detecting changes in whole-tumour oxygenation induced by carbogen (5% CO2+95% O2) inhalation of the host. Adult WAG/Rij rats with rhabdomyosarcomas growing subcutaneously in the lower flank were imaged when tumours reached sizes between 1 and 11 cm3 (n=12). Air and carbogen were alternatively supplied at 2 l/min using a snout mask. Imaging was done on a 1.5-T MR scanner using a T2*-weighted gradient-echo, echo-planar imaging (GE-EPI) sequence. Analysis of the whole-tumour EPI images was based on statistical parametric maps. Voxels with and without signal intensity changes (SIC) were recorded. Significance thresholds were set at p<0.05, corrected for multiple comparisons. In continuous air breathing condition, 3 of 12 tumours showed significant negative SIC and 1 tumour had a clear-cut positive SIC. The remaining tumours showed very little or no change. When switching to carbogen breathing, the SIC were significantly positive in 10 of 12 tumours. Negative SIC were present in 4 tumours, of which three were simultaneously characterised by positive SIC. The overall analysis indicated that 6 of the 12 tumours could be considered as strong positive responders to carbogen. Our research demonstrates the applicability of fMRI GE-EPI at 1.5 T to study whole-tumour oxygenation non-invasively. The observed negative SIC during air condition may reflect the presence of transient hypoxia during these measurements. Selection of tumours on the basis of their individual response to carbogen is possible, indicating a role of such non-invasive measurements for using tailor-made treatments. [ABSTRACT FROM AUTHOR]