Kate Goodchild

BOLD MRI of human tumor oxygenation during carbogen breathing

An MRI method is described for demonstrating improved oxygenation of human tumors and normal tissues during carbogen inhalation (95% O2, 5% CO2). T  *2 ‐weighted gradient‐echo imaging was performed before, during, and after carbogen breathing in 47 tumor patients and 13 male volunteers. Analysis of artifacts and signal intensity was performed. Thirty‐six successful tumor examinations were obtained. Twenty showed significant whole‐tumor signal increases (mean 21.0%, range 6.5–82.4%), and one decreased (−26.5 ± 8.0%). Patterns of signal change were heterogeneous in responding tumors. Five of 13 normal prostate glands (four volunteers and nine patients with nonprostatic tumors) showed significant enhancement (mean 11.4%, range 8.4–14.0%). An increase in brain signal was seen in 11 of 13 assessable patients (mean 8.0 ± 3.7%, range 5.0–11.7%). T  *2 ‐weighted tumor MRI during carbogen breathing is possible in humans. High failure rates occurred due to respiratory distress. Significant enhancement was seen in 56%, suggesting improved tissue oxygenation and blood flow, which could identify these patients as more likely to benefit from carbogen radiosensitization. J. Magn. Reson. Imaging 2001;14:156–163.

Experience with dose escalation using CHARTWEL (continuous hyperfractionated accelerated radiotherapy weekend less) in non-small-cell lung cancer

Results from the multicentre randomized trial of CHART (continuous, hyperfractionated, accelerated radiotherapy) in non-small-cell lung cancer (NSCLC) showed a significant increase in survival (P=0.004) compared with conventional radiotherapy and a therapeutic benefit relative to late radiation-induced morbidity. However, 60% of patients died because of failure to control locoregional disease. These findings have stimulated interest in assessing the feasibility of dose escalation using a modified CHART schedule. Acute and late morbidity with a CHARTWEL (CHART WeekEnd Less) schedule of 54 Gy in 16 days was compared with that observed with 60 Gy in 18 days in patients with locally advanced NSCLC. The incidence and severity of dysphagia and of analgesia were scored using a semiquantitative clinical scale. Late radiation-induced morbidity, namely pulmonary, spinal cord and oesophageal strictures, were monitored using clinical and/or radiological criteria. Acute dysphagia and the analgesia required to control the symptoms were more severe and lasted longer in patients treated with CHARTWEL 60 Gy (P< or = 0.02). However, at 12 weeks, oesophagitis was similar to that seen with 54 Gy and did not lead to consequential damage. Early radiation pneumonitis was not increased but, after 6 months, there was a higher incidence of mild pulmonary toxicity compared with CHARTWEL 54 Gy. No cases of radiation myelitis, oesophageal strictures or of grade 2 or 3 lung morbidity have been encountered. CHARTWEL 60 Gy resulted in an enhancement of oesophagitis and grade 1 lung toxicity compared with CHARTWEL 54 Gy. These were of no clinical significance, but may be important if CHARTWEL is used with concomitant chemotherapy. These results provide a basis for further dose escalation or the introduction of concurrent chemotherapy.

Carbogen and nicotinamide in the treatment of bladder cancer with radical radiotherapy

Carbogen and nicotinamide have been evaluated in a phase II study as hypoxia-modifying agents during radical radiotherapy for bladder cancer using a standard daily 20-fraction schedule. Three groups of patients have received (a) nicotinamide alone, given orally in a dose of 80 mg kg(-1) daily with 52.5 Gy in 20 fractions over 4 weeks, (b) carbogen alone, with 50 Gy in 20 fractions over 4 weeks, and (c) carbogen and nicotinamide, with 50-52.5 Gy in 20 fractions over 4 weeks. Ten patients were treated in each group. All patients completed carbogen and radiotherapy as prescribed, but only 45% completed daily nicotinamide over the 4-week treatment period. The end points of this study were acute bowel and bladder morbidity and local control at cystoscopy 6 months after treatment. An expected level of acute bowel and bladder morbidity was seen that reverted to normal in most patients by 12 weeks with no difference between the three treatment groups. Complete response rates at 6 months were seven out of ten (100%) in the nicotinamide alone group, nine out of ten (90%) in the carbogen alone group and seven out of ten (70%) in the carbogen and nicotinamide group. It is concluded that carbogen and nicotinamide may improve the results of daily fractionated radiotherapy in bladder cancer and that further evaluation is required.

18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in the Assessment of Occult Primary Head and Neck Cancers — An Audit and Review of Published Studies

AIMS To assess the value of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with squamous cell and undifferentiated cancer neck nodes and no primary site on conventional assessment. MATERIALS AND METHODS Seventy-eight patients with neck nodal metastases from an unknown primary cancer were studied. PET/CT was carried out in all patients, 1h after FDG injection. RESULTS Uptake suspicious of an occult primary cancer was found in 46/78 (59.0%) patients. Subsequent investigations confirmed a primary site in the base of the tongue in 14, pharyngeal palatine tonsil in 14, post cricoid in one, lung in one. PET/CT diagnosed primary cancers in 30/78 patients (38.5%); sensitivity, specificity, positive predictive value, negative predictive value: 30/30 (100.0%), 32/48 (66.7%), 30/46 (65.2%), 32/32 (100.0%), respectively. PET/CT detected additional disease in four patients: contralateral nodal disease in two, mediastinal nodal disease in one and liver metastases in one. CONCLUSIONS FDG PET/CT is of value in the assessment of patients with occult head and neck primary cancers. However, false-positive results remain a limitation of the investigation.

Potential novel application of dual time point SUV measurements as a predictor of survival in head and neck cancer.

ObjectivesTo examine the potential of pre-treatment dual time point [18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) as a tool for improving the assessment of head and neck cancer. Two main areas were investigated: (a) optimum time to start FDG scanning post-injection and (b) potential of SUV obtained from dual time point scanning as a prognostic indicator of survival. MethodsTwelve patients with advanced head and neck cancer were prospectively studied. Each patient was scanned using a Siemens Ecat Exact-47 PET scanner at 1 h and 2 h post-injection. Maximum tumour uptake (SUVt) and ratio of maximum tumour/normal tissue uptake (SUVt/n) were recorded. The optimal time to initiate scanning was investigated by comparing SUVt and SUVt/n with the decision made by two experienced observers as to which scan they preferred to report from, given the choice of the 1 h and 2 h scan in each patient. ResultsA significant difference between 1 h and 2 h SUVt (P<0.004, paired t-test) and between 1 h and 2 h SUVt/n (P<0.0003, paired t-test) was observed. All 2 h SUVt and SUVt/n were greater in magnitude than their respective 1 h SUVt and SUVt/n counterparts. The two observers reported an identical number of lesions from the 1 h and 2 h scans but preferred the 2 h data. ConclusionsTumour stage and the percentage difference in 1 h and 2 h SUVt showed potential as prognostic indicators of long-term survival.

Evaluation of normal FDG uptake in palatine tonsil and its potential value for detecting occult head and neck cancers: a PET CT study.

ObjectiveThe aims of the study were to (1) evaluate the range of physiological FDG uptake in normal pharyngeal palatine tonsil, and (2) investigate the possibility of establishing a cut-off threshold to distinguish between normal pharyngeal palatine tonsil FDG uptake from occult pharyngeal palatine tonsil primary cancer. MethodsFDG PET CT of 43 consecutive patients with a low risk of head and neck cancer were reviewed by two observers. Axial PET CT was used to identify foci of FDG uptake related to the pharyngeal palatine tonsil. The highest standardized uptake value, SUVmax, of the left and right pharyngeal palatine tonsil was calculated. Similar analysis was performed on 10 consecutive patents with histologically proven occult pharyngeal palatine tonsil primary cancer. ResultsThe mean SUVmax of the 43 right pharyngeal palatine tonsils was 4.82 (range, 1.16–12.74) and 4.68 (range, 0.88–13.65) for the 43 left pharyngeal palatine tonsils with no statistical difference observed (P=0.4). Normal pharyngeal palatine tonsil uptake was generally symmetrical and there was a positive correlation between SUVmax from the left and right sides which was statistically significant (r=0.9, P<0.0001). In the same patient the difference in SUVmax between left and right pharyngeal palatine tonsil ranged from 0.01 to 2.66 and patients with occult pharyngeal palatine tonsil primary cancer it ranged from 0.85 to 11.08. ROC analysis showed that an ‘SUVmax difference’ cut-off of 0.83 would achieve a sensitivity of 100% and specificity of 81% for detecting occult pharyngeal palatine tonsil primary cancers. ConclusionsThere is considerable variation of pharyngeal palatine tonsil FDG uptake in patients with no pharyngeal palatine tonsil primary cancer. However, in the same patient there is generally only a small difference in uptake between left and right sides. The absolute difference in SUVmax between left and right pharyngeal palatine tonsil is a potentially useful parameter for distinguishing between normal FDG uptake in pharyngeal palatine tonsil from occult pharyngeal palatine tonsil primary cancer.

Chemoradiotherapy with or without Induction Chemotherapy for Locally Advanced Pancreatic Cancer: a UK Multi-institutional Experience

AIMS The optimal management for patients with unresectable locally advanced adenocarcinoma of the pancreas (LAPC) is unclear. The aim of this study was to determine the outcome of patients treated with chemoradiotherapy (CRT) with or without induction chemotherapy. MATERIALS AND METHODS We conducted a multi-centre retrospective analysis of 48 patients with biopsy-proven LAPC treated with CRT in four regional oncology centres in the UK between March 2000 and October 2007. The prescribed radiotherapy dose was 4500-5040 cGy in 25-28 fractions and was given concurrent with gemcitabine (n=37), gemcitabine/cisplatin (n=9), 5-fluorouracil (n=1) or capecitabine (n=1). RESULTS Four patients (8.3%) did not complete the intended treatment due to CRT-related toxicities. The disease control rate (Objective response rate (ORR) and stable disease (SD)) was 81.3%. The median overall survival was 17 months (range 5-66 months). In subgroup analysis, a trend towards improved survival was seen in patients who completed the intended treatment (17.1 months vs 11.0 months, P=0.06) and in patients undergoing surgery (27 months vs 16 months, P=0.023). CONCLUSIONS This is the largest reported series from the UK focussing on patients who received CRT for pancreas cancer. It shows that it is possible to deliver pancreatic CRT with acceptable toxicity. Induction chemotherapy followed by gemcitabine-based CRT shows promising activity and should be evaluated in phase III studies.

The modification of human tumour blood flow using pentoxifylline, nicotinamide and carbogen

AIM To assess the effect of combining oral nicotinamide, oral pentoxifylline and carbogen gas (2% CO2, 98% O2) breathing on human tumour red cell flux. METHODS AND MATERIALS Microregional red blood cell flux was measured in accessible tumour nodules using laser Doppler microprobes in 11 patients with histologically proven malignancy. Patients received single oral doses of nicotinamide 40 mgkg-1 and pentoxifylline 1200 mg 2h before a 10-min period of carbogen gas breathing, corresponding to peak plasma concentrations of these drugs. Red cell flux in up to six microregions in each tumour was measured for 30 min, recording pre-, during and post-carbogen breathing for 10 min each. RESULTS Data from ten of the 11 patients could be assessed. The red cell flux in 48 microregions was analysed and the mean red cell flux was calculated. A mean relative increase in red cell flux of 1.18 (+/-0.09, 95% confidence interval (CI)) was observed after 6 min of carbogen breathing, 2h after the administration of nicotinamide and pentoxifylline. This compares to relative increases of 1.4 (+/-0.39, 95%CI) after nicotinamide with carbogen and 1.15 (+/-0.10, 95%CI) after pentoxifylline with carbogen. These differences are not statistically significant (P>0.05). The increased red cell flux persisted after the cessation of carbogen gas breathing. CONCLUSIONS A combination of pentoxifylline, nicotinamide and carbogen produces an increase in human tumour red cell flux, similar to that observed when each of the drugs are used alone with carbogen breathing.

A feasibility study of continuous hyperfractionated accelerated radiotherapy (CHART) and brachytherapy in patients with early oral or oropharyngeal carcinomas

Overall time is important in the curative treatment of head and neck cancer (Dische, S., Saunders, M.I., Barrett, A., Harvey, A., Gibson, D., Parmar, M., 1997, Radiother. Oncol., 44:123-136). Results are presented on outcome and morbidity in ten patients with head and neck cancer treated with external beam irradiation (CHART protocol) and interstitial implantation, completing treatment in 12 days. Local control and overall survival at 5 years was 67%. Acute and late morbidity was acceptable giving scope for dose escalation.