[en] Thirteen patients with unresectable non small cell lung cancer were treated with radical radiotherapy and carboplatin administered in order to ascertain the toxicity of concurent carboplatin/radiotherapy. The first 6 patients were treated to a total dose of 60 Gy in 30 fractions in 6 weeks, with carboplatin 70 mg/m² /day on days 1 to 5 during weeks 1 and 5 of radiotherapy. The remaining 7 patients were given 60 Gy in 30 fractions in 3 weeks, treating twice a day (accelerated fractionation). Carboplatin was given as above but only during week 1 of radiotherapy. Twelve patients completed radiotherapy without interruption but 2 patients developed grade 3 neutropenia. Major toxicity was oesophagitis, one patient requiring nasogastric feeding. Average duration of dysphagia (any grade) in the accelerated fractionation group was 21 weeks. Four patients achieved good partial responses even though initial tumour volume was large. It is concluded that this treatment is associated with increased but acceptable early mucosal toxicity. 6 refs., 1 tab., 1 fig

[en] Full text: Lymphoma is the commonest clinical indication for FDG-PET world wide although published data for its effectiveness is limited. The aim of this study was to assess the incremental staging, restaging and therapy monitoring value of PET vs CT. The case notes and CT scan reports of patients having FDG-PET scans for lymphoma at the RAH were reviewed retrospectively. 625 PET scans on 548 patients had been performed at the RAH between 14 September 2000 and 1 November 2001. 142 scans (23%) were for 'lymphoma' in 99 patients (18%). Excluding remote external referrals, follow-up data was available for 73 patients (112 scans) with confirmed non-CNS lymphoma. Disease demonstrated by CT and PET was compared for each of the three major clinical indications for PET which were: 1) primary staging, 2) restaging for suspected recurrence and 3) assessment of therapy response. In 3 patients both CT and PET showed discordant and incremental disease sites. The most dramatic discordant additional disease findings usually occurred in PET scans performed for restaging. The major additional information provided by PET so far has been in restaging for suspected relapse where it frequently shows much more extensive disease than does conventional CT. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc

[en] The primary objectives are to compare head and neck cancer patients receiving standard radiation therapy, randomised to amifostine (200mg/m2) or to placebo (normal saline) with respect to the incidence of grade 2 or higher acute and late salivary gland toxicities. The study drug is delivered as a 3-minute intravenous infusion 15-30 mins prior to each fraction. Chemotherapy is delivered before the study drug. Twenty patients (18 males and 2 females) have been entered into the pilot study, 19 with stage III/ IV disease. Seventeen patients have completed treatment, their age ranging from 37 to 74 years. Seventeen patients were referred postoperatively. All patients commenced radiation therapy within one-half hour of the study drug. Only 4 episodes of hypotension have been recorded, all less than 30 mmHg. One incidence of grade 3 vomiting (which responded to cessation of chemotherapy) was recorded and one case of neutropenia, both secondary to chemotherapy. Three serious adverse events were recorded, including 1 patient who died 3 weeks after completing chemoradiotherapy (pulmonary embolus), 2 hospital admissions, one for weight loss, neutropenia, depression and vomiting, and a second for an allergic cutaneous reaction. 15/17 received the full study drug: 1 patient withdrew after the first fraction and, in the second secondary to the cutaneous reaction. All patients received the prescribed radiation dose. Seven patients received chemotherapy (cisplatin), 1 ceasing treatment after 3 weeks (grade 3 neutropenia). All patients were well hydrated. Follow-up is short (mean of 7.25 months). Complete response was achieved in 13, partial response in 1. Three patients have relapsed, only 1 of who is in second complete remission. The trial is running smoothly, and has recently been adopted as a multi-centre trial under the auspices of TROG, aiming to recruit 200 eligible patients, who commenced radiation and amifostine/placebo

[en] The mechanisms postulated to be responsible for the accelerated repopulation of squamous cell carcinomas during radiotherapy are the loss of asymmetry of stem cell division, acceleration of stem cell division, abortive division and/or recruitment of the non-cycling cell with proliferative capacity. Although accelerated repopulation was observed with recruitment and accelerated cell cycles, it was not sufficient to cause an observable change to the survival curve. However, modelling the loss of asymmetry in stem cell division has reshaped the curve with a 'growth' shoulder. Cell recruitment was not found to be a major contributor to accelerated tumour repopulation. A more significant contribution was provided through the multiplication of surviving tumour stem cells during radiotherapy, by reducing their cell cycle time, and due to loss of asymmetry of stem cell division

[en] The aim of the present work was to implement the kinetics of cisplatin into a previously developed tumour growth model and to simulate the combined cisplatin-radiotherapy treatment with the emphasis on time sequencing and scheduling of drug and radiation. An investigation into whether the effect of cisplatin-radiation is determined by independent cell kill or by cisplatin-produced radiosensitization was also undertaken. It was shown that cisplatin administered before radiation conferred similar tumour control to the post-radiation sequencing of the drug. The killing effect of the combined modality treatment on tumour increased with the increase in cell recruitment. Furthermore, the individual cell kill produced by the two cytotoxins led to an additive only tumour response when the treatments were given concurrently, suggesting that for a synergistic effect, cisplatin must potentiate the effect of radiation, through the radiosensitizing mechanisms addressed in the literature. It was concluded that the optimal timing of cisplatin should be close to radiation. The model showed that daily administration of cisplatin led to a 35% improvement of tumour control as compared to radiation alone, while weekly cisplatin has improved radiotherapy by only 6%

[en] Full text: Since Rosenberg's initial discovery, cisplatin has become one of the most effective anticancer drugs, with particular significance in head and neck cancer. For advanced disease, where the tumour is unresectable, radiotherapy and chemotherapy, either singularly or combined, remain the possible therapeutic modalities. The majority of the trials using a combination of cisplatin and radiation obtained much better results than the single-agent trials. But the best schedule, dosage and timing between radiation and drug administration are still unknown. Many positive steps were however made to eliminate the cisplatin-produced side effects, as much as possible. The tendency in current trials is to fractionate the drug dose by daily administration and also to hyperfractionate the radiation. In this way the long-term benefits are improved and the toxicity is better tolerated

[en] Full text: A study into the optimal fractionation and schedule in combined chemo-radiotherapy for head and neck cancer has imposed the development of a computer model of tumour growth. The model is based on biological parameters, and characterises tumour growth and eventual tumour regression when chemo-radiotherapy is used. Tumour growth starting from a single stem cell is modelled using the Monte Carlo method. The type of the cell function, their relative proportions on mitosis, their proliferative capacity, the duration of the four phases of the cell cycle, the mean cell cycle time, and the cell loss due to natural causes are the main parameters of the basic model. A Gaussian distribution function operates in establishing the cell cycle time, with a mean value of 26 hours, while the cell type is sampled from a uniform distribution. With the established model, the sensitivity of the developed tumour's cell population to the stem, proliferative and non proliferative ratio at mitosis was assessed. The present model accurately reflects the exponential distribution of cells along the cell cycle (70% cells in G1 phase, 15% in S, 10% in G2, 5% in M) of a developed tumour as described in the literature. The proportion of stem, finitely proliferating and resting cells during tumour growth is maintained within their biological limits (2% stem. 23% finitely proliferating, 75% nonproliferating cells). The ratio (R=3) between the time necessary to develop a clinically detectable tumour (10⁹ cells) and the time to grow to its lethal size (10¹² cells) is in accordance with the biological data when tumour volume is compared for the two periods (30 doublings and 10 doublings respectively). Computer simulation can illustrate the biological growth of a tumour and the cell distribution along the cell cycle. These distributions may than be used in the assessment of tumour response to radiotherapy and to specific chemotherapeutic agents. Copyright (2001) Australasian College of Physical Scientists and Engineers in Medicine

[en] Although chemotherapy has revolutionized the treatment of haematological tumours, in many common solid tumours the success has been limited. Some of the reasons for the limitations are: the timing of drug delivery, resistance to the drug, repopulation between cycles of chemotherapy and the lack of complete understanding of the pharmacokinetics and pharmacodynamics of a specific agent. Cisplatin is among the most effective cytotoxic agents used in head and neck cancer treatments. When modelling cisplatin as a single agent, the properties of cisplatin only have to be taken into account, reducing the number of assumptions that are considered in the generalized chemotherapy models. The aim of the present paper is to model the biological effect of cisplatin and to simulate the consequence of cisplatin resistance on tumour control. The 'treated' tumour is a squamous cell carcinoma of the head and neck, previously grown by computer-based Monte Carlo techniques. The model maintained the biological constitution of a tumour through the generation of stem cells, proliferating cells and non-proliferating cells. Cell kinetic parameters (mean cell cycle time, cell loss factor, thymidine labelling index) were also consistent with the literature. A sensitivity study on the contribution of various mechanisms leading to drug resistance is undertaken. To quantify the extent of drug resistance, the cisplatin resistance factor (CRF) is defined as the ratio between the number of surviving cells of the resistant population and the number of surviving cells of the sensitive population, determined after the same treatment time. It is shown that there is a supra-linear dependence of CRF on the percentage of cisplatin-DNA adducts formed, and a sigmoid-like dependence between CRF and the percentage of cells killed in resistant tumours. Drug resistance is shown to be a cumulative process which eventually can overcome tumour regression leading to treatment failure

[en] The aims of this study were to evaluate the feasibility, practicality, efficacy and safety of the delivery of accelerated partial breast irradiation using the MammoSite for the boost phase. Six patients aged 53-69 years with stage T1N0, T2N0, Grade l-ll invasive ductal carcinoma received 9-10 Gy prescribed at 1 cm from the MammoSite balloon surface in two fractions of 4.5-5 Gy 6 h apart. The MammoSite was inserted 20-37 days postoperatively. External beam radiation therapy to the whole breast commenced 1-5 days after accelerated partial breast irradiation. The maximum skin dose ranged from 3 to 9 Gy. The skin-cavity distance ranged from 7 to 19 mm. Local discomfort resolved as the scar healed spontaneously within 3-5 days. No Grade III or higher acute toxicity or local infection was recorded. The ease of insertion and accuracy of dosimetry makes the MammoSite suitable for use in properly selected women with early-stage breast cancer in a trial setting

[en] Full text: Cancer stem cells (CSCs) play a fundamental role in tumour progression, metastases and recurrence. These are the most treatment resistant of tumour cells, accelerating their replication and tumour repopulation in response to tumour depletion. The human papillomavirus (HPV) has emerged as a discrete aetiology in head and neck cancers (HNC). They demonstrate consistently better responses to radiotherapy initiating several clinical trials to de-escalate treatment. This study investigates the in vitro differences in CSC responses in head and neck cancers to radiation in terms of their HPV aetiology. Six HNC cell lines were investigated. UM-SCC-47, UPCI-SCC-090 and UPCI-SCC-154 are HPV+ and UM-SCC-1, UM-SCC-17a and UM-SCC-22a are HPV-. Cells were irradiated in T25 flasks with 4 Gy using a Varian 6 MV linac and a RS2000 irradiator at 160 kVp and 25 mA. Flasks were filled with medium, encased in a paraffin wax block and mounted on 7 cm of RW3 to provide full scatter conditions. Sham-irradiated flasks were used as controls. CSC proportions of cell populations were measured at 24, 48 and 72 hours, and again at 10 days post irradiation. CSCs were identified by putative cellular markers CD44 and aldehyde dehydrogenase (ALDH), using flow cytometry. Results Triplicate analysis of non-irradiated UM-SCC-47 cell cultures showed a mean CD44+/ALDH+ population to be 2.87%+0.219, 5-fold that of the UM-SCC-1 population which was 0.57%+0.077. UM-SCC-47 and UM-SCC-1 showed increased ALDH+/CD44+ proportions of population following 4 Gy irradiation. The proportional increase for UM-SCC-47 was 3 to 4 times the control within 72 hrs post irradiation. After 10 days these cultures no longer presented significant differences in CSC population against the control. UM-SCC-1 showed the most significant CSC increase 24 hrs post irradiation and a persisting elevation in CSCs 10 days after irradiation. CSCs display significant heterogeneity between cell lines warranting investigation of the effect aetiology has on intrinsic population numbers and treatment responsiveness. (author)