Preclinical safety and antitumor efficacy of insulin combined with irradiation.

Background And Purpose: We have previously reported that insulin significantly enhances tumor oxygenation (pO(2)) and increases radiation-induced tumor regrowth delay in experimental models. Considering the large radiosensitizing effect, clinical trials might be envisioned. The aim of the present pre-clinical study was to obtain a more complete set of safety and efficacy data which would further justify the commencement of such clinical trials.

Microsatellite alterations in head and neck squamous cell carcinoma and relation to expression of pimonidazole, CA IX and GLUT-1.

Background And Purpose: Because the locoregional control for HNSCC is still disappointing, research efforts focus on the exploration of new molecular markers located in both tumour and microenvironment, which could help stratify patients. The aim of the present work was therefore first to assess microsatellite alterations and hypoxia in HNSCC as possible molecular markers. Second, a relation between both was investigated, as hypoxia is known to select for genetic alterations.

Epithelial-myoepithelial carcinoma of the submandibular gland with symptomatic lung metastases treated with chemotherapy.

This report concerns a patient with symptomatic lung metastases from an epithelial-myoepithelial carcinoma of the submandibular gland. Although the efficacy of chemotherapy is unknown in this disease, our patient was treated with cisplatin combined with 5-fluorouracil and later with paclitaxel and cyclophosphamide. Chemotherapy allowed disease stabilization and relief of the pulmonary symptoms.

Reversal of temporal and spatial heterogeneities in tumor perfusion identifies the tumor vascular tone as a tunable variable to improve drug delivery.

Maturation of tumor vasculature involves the recruitment of pericytes that protect the endothelial tubes from a variety of stresses, including antiangiogenic drugs. Mural cells also provide mature tumor blood vessels with the ability to either relax or contract in response to substances present in the tumor microenvironment. The observed cyclic alterations in tumor blood flow and the associated deficit in chemotherapeutic drug delivery could in part arise from this vasomodulatory influence.

Primary combined squamous and small cell carcinoma of the larynx: Report of two cases and discussion of treatment modalities.

Combined small cell carcinoma (SMCC) of the larynx consists of SMCC admixed with a component of squamous cell carcinoma or adenocarcinoma. These tumors are very rare and, to date, only a few cases have been fully described. This points out the lack of information available about the correct management of these patients.

Effects of irradiation on bone remodelling around mandibular implants: an experimental study in dogs.

This research focuses on the effects of radiotherapy on bone remodelling around mandibular implants in dogs. After bilateral extraction of the mandibular premolars and first 2 molars, each of 11 beagles received 8 mandibular implants. Four animals were irradiated 4 weeks after implantation and 4 others 8 weeks before implantation; the remaining 3 did not receive radiotherapy.

Proposal for the delineation of the nodal CTV in the node-positive and the post-operative neck.

Background And Purpose: In 2003, a panel of experts published a set of consensus guidelines regarding the delineation of the neck node levels (Radiother Oncol, 2003; 69: 227-36). These recommendations were applicable for the node-negative and the N1-neck, but were found too restrictive for the node-positive and the post-operative neck.

Patients And Methods: In this framework, using the previous recommendations as a backbone, new guidelines have been proposed taking into account the specificities of the node-positive and the post-operative neck.

The current status of FDG-PET in tumour volume definition in radiotherapy treatment planning.

Positron emission tomography (PET) scan, mainly using 18 F-fluoro-deoxyglucose (FDG) as a tracer, is currently widely accepted as a diagnostic tool in oncology. It may lead to a change in staging and therefore in treatment management. PET can also be used to define the target volume in radiation treatment planning and to evaluate treatment response.

Detection of tumour hypoxia: comparison between EF5 adducts and [18F]EF3 uptake on an individual mouse tumour basis.

In the framework of the preclinical validation of the hypoxic tracer [(18)F]EF3, a comparison was performed between uptake of [(18)F]EF3 and EF5 adducts detected by immunofluorescence in MCa-4, FSA, FSAII, Sa-NH and NFSA tumour-bearing mice. Mice were allowed to breath carbogen (5% CO(2), 95% O(2)), 21% oxygen or 10% oxygen. A significant correlation (r (2)=0.

Impact of the type of imaging modality on target volumes delineation and dose distribution in pharyngo-laryngeal squamous cell carcinoma: comparison between pre- and per-treatment studies.

Background And Purpose: It has been shown that the use of pre-treatment FDG-PET impacted on the GTV delineation of pharyngo-laryngeal tumors. The goals of this study were to evaluate (1) the impact of FDG-PET GTV on dose distribution, and (2) the impact of per-treatment re-imaging on target volume delineation and dose distribution.

Materials And Methods: Eighteen patients with squamous cell carcinoma of the oropharynx or larynx/hypopharynx were treated with curative intent by forward planning IMRT.

Botulinum toxin potentiates cancer radiotherapy and chemotherapy.

Purpose: Structural and functional abnormalities in the tumor vascular network are considered factors of resistance of solid tumors to cytotoxic treatments. To increase the efficacy of anticancer treatments, efforts must be made to find new strategies for transiently opening the tumor vascular bed to alleviate tumor hypoxia (source of resistance to radiotherapy) and improve the delivery of chemotherapeutic agents. We hypothesized that Botulinum neurotoxin type A (BoNT-A) could interfere with neurotransmitter release at the perivascular sympathetic varicosities, leading to inhibition of the neurogenic contractions of tumor vessels and therefore improving tumor perfusion and oxygenation.

Tumor control probability (TCP) and normal tissue complication probability (NTCP) in head and neck cancer.

Clinical radiobiology is concerned with the relationship between a given radiation dose and the resulting biological effect on tumors and normal tissues, as well as with all confounding factors related to the delivery of radiation (e.g. dose per fraction, overall treatment time, volume of tumor/normal tissue irradiated, concomitant use of chemotherapy) and/or associated with preexisting conditions of the host (e.

Early reoxygenation in tumors after irradiation: determining factors and consequences for radiotherapy regimens using daily multiple fractions.

Purpose: To characterize changes in the tumor microenvironment early after irradiation and determine the factors responsible for early reoxygenation.

Methods And Materials: Fibrosarcoma type II (FSaII) and hepatocarcinoma transplantable liver tumor tumor oxygenation were determined using electron paramagnetic resonance oximetry and a fiberoptic device. Perfusion was assessed by laser Doppler, dynamic contrast-enhanced MRI, and dye penetration.

Tumor radiosensitization by antiinflammatory drugs: evidence for a new mechanism involving the oxygen effect.

We hypothesized that nonsteroidal antiinflammatory drugs (NSAIDs) might enhance tumor radiosensitivity by increasing tumor oxygenation (pO2), via either a decrease in the recruitment of macrophages or from inhibition of mitochondrial respiration. The effect of four NSAIDs (diclofenac, indomethacin, piroxicam, and NS-398) on pO2 was studied in murine TLT liver tumors and FSaII fibrosarcomas. At the time of maximum pO2 (t(max), 30 minutes after administration), perfusion, oxygen consumption, and radiation sensitivity were studied.

Prevalence of lymph nodes in the apex of level V: a plea against the necessity to dissect the apex of level V in mucosal head and neck cancer.

Background: We assessed the prevalence of histologically proven normal or invaded lymph nodes in the apex of level V.

Methods: Seventy neck dissections were performed in 41 patients with mucosal head and neck squamous cell carcinoma (SCC). Fifty-one neck dissections were performed in 30 previously untreated patients (group 1); 19 neck dissections were carried out in 11 patients previously irradiated (group 2).

Carotid stenting for impending carotid blowout: suitable supportive care for head and neck cancer patients?

Background: Carotid blowout (CB) represents a dramatic end-of-life situation for palliative head and neck cancer patients, their relatives and caregivers. Recently, endovascular therapy has been proposed for head and neck surgical patients. Preliminary reports showed a better outcome with less morbidity compared to the previous treatment modalities.

Intestinal crypt regeneration in mice: a biological system for quality assurance in non-conventional radiation therapy.

Background And Purpose: The Relative Biological Effectiveness (RBE) of 8 fast-neutron beams, 5 proton beams and 1 carbonion beam was determined using as biological criterion intestinal crypt regeneration in mice, i.e. an in vivo system.

General principles for prescribing, recording and reporting a therapeutic irradiation.

Exchange of clinical information is essential for the development and progress in radiation oncology. This goal can be achieved only through a general harmonization on methods of reporting. The ICRU has been involved for several decades in a continuous effort to harmonize reporting of dose and to standardize methods used to determine the doses and points or volumes where these doses are delivered.

Radiobiological rationale and patient selection for high-LET radiation in cancer therapy.

The rationale for introducing ion beams in cancer therapy is the high level of physical selectivity that can be achieved with ions, equal or even better than with proton beams or modern photon techniques, as well as the potential advantage of high-LET radiations for some tumour types and sites. The radiobiological arguments for high-LET radiation in cancer therapy are reviewed: reduction of OER in the case of hypoxic and poorly-reoxygenating tumours, and the lesser importance of repair phenomena which are a problem in controlling repair-proficient photon-resistant tumours. Fast neutrons were the first type of high-LET radiation used clinically, and were often applied under suboptimal technical conditions.

Intraoperative validation of CT-based lymph nodal levels, sublevels IIa and IIb: is it of clinical relevance in selective radiation therapy?

Purpose: The objectives of this study are to discuss the intraoperative validation of CT-based boundaries of lymph nodal levels in the neck, and in particular the clinical relevance of the delineation of sublevels IIa and IIb in case of selective radiation therapy (RT).

Methods And Materials: To validate the radiologically defined level contours, clips were positioned intraoperatively at the level boundaries defined by surgical anatomy. In 10 consecutive patients, clips were placed, at the time of a neck dissection being performed, at the most cranial border of the neck.

Inter-observer variability in the delineation of pharyngo-laryngeal tumor, parotid glands and cervical spinal cord: comparison between CT-scan and MRI.

Background And Purpose: The goal of this study was to compare the inter-observer variability between CT and MRI for the delineation of pharyngo-laryngeal SCC, parotid glands and spinal cord.

Patients And Methods: Twenty pharyngo-laryngeal tumors were delineated by five observers on CT and MRI, using consistent delineation guidelines. Spinal cords and parotid glands were also delineated on CT and MRI by three observers.

Efficient multi-modal dense field non-rigid registration: alignment of histological and section images.

We describe a new algorithm for non-rigid registration capable of estimating a constrained dense displacement field from multi-modal image data. We applied this algorithm to capture non-rigid deformation between digital images of histological slides and digital flat-bed scanned images of cryotomed sections of the larynx, and carried out validation experiments to measure the effectiveness of the algorithm. The implementation was carried out by extending the open-source Insight ToolKit software.

Intensity modulated radiation therapy in head and neck squamous cell carcinoma: state of the art and future challenges.

Intensity-modulated radiation therapy (IMRT) for head and neck (HN) tumors refers to a new approach to the whole treatment procedure from patient immobilization to beam delivery. Implementation of IMRT thus requires knowledge of setup uncertainties, adequate selection and delineation of target volumes based on clinical examination and optimal imaging modalities, appropriate specification and dose prescription regarding dose-volume constraints, and ad hoc quality control of both the clinical and physical aspects of the whole procedure. A large number of issues still need to be resolved and/or further refined, such as the optimal selection and delineation of the target volume in particular, with the introduction of functional imaging, and a better integration of improved dose distribution into the fractionation strategy.