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As cancer therapy becomes more effective, allowing patients to live longer, the long-term morbidity of treatment assumes greater significance. Trastuzumab (Herceptin ® ), a monoclonal antibody that targets the epidermal growth factor, has proven efficacy in breast cancer patients but is also known to be cardiotoxic. Left ventricular ejection fraction (LVEF), a measure of cardiac function, is commonly used to evaluate patients receiving trastuzumab by Multiple Gated Acquisition (MUGA) isotope scans. In this paper, we have assessed the utility of previously published ventricular synchrony parameters in patients undergoing trastuzumab therapy. In addition, we apply Approximate Entropy (ApEn) to MUGA images, as a new measure of cardiac dysfunction and have evaluated its utility in the same patients. A significant change in LVEF ( p = 0.015) and ApEn ( p = 0.020) but not ventricular synchrony measures were observed over the course of treatment in these patients. The results suggest that ApEn provides a useful measure of cardiac function and synchrony.

BACKGROUND: The authors compared gemcitabine and carboplatin (GC) with mitomycin, ifosfamide, and cisplatin (MIC) or mitomycin, vinblastine, and cisplatin (MVP) in patients with advanced nonsmall cell lung carcinoma (NSCLC). The primary objective was survival. Secondary objectives were time to disease progression, response rates, evaluation of toxicity, disease-related symptoms, World Health Organization performance status (PS), and quality of life (QoL). METHODS: Three hundred seventy-two chemotherapy-naive patients with International Staging System Stage III/IV NSCLC who were ineligible for curative radiotherapy or surgery were randomized to receive either 4 cycles of gemcitabine (1000 mg/m(2) on Days 1, 8, and 15) plus carboplatin (area under the serum concentration-time curve, 5; given on Day 1) every 4 weeks (the GC arm) or MIC/MVP every 3 weeks (the MIC/MVP arm). RESULTS: There was no significant difference in median survival (248 days in the MIC/MVP arm vs. 236 days in the GC arm) or time to progression (225 days in the MIC/MVP arm vs. 218 days in the GC arm) between the 2 treatment arms. The 2-year survival rate was 11.8% in the MIC/MVP arm and 6.9% in the GC arm. The 1-year survival rate was 32.5% in the MIC/MVP arm and 33.2% in the GC arm. In the MIC/MVP arm, 33% of patients responded (4 complete responses [CRs] and 57 partial responses [PRs]) whereas in the GC arm, 30% of patients responded (3 CRs and 54 PRs). Nonhematologic toxicity was comparable for patients with Grade 3-4 symptoms, except there was more alopecia among patients in the MIC/MVP arm. GC appeared to produce more hematologic toxicity and necessitated more transfusions. There was no difference in performance status, disease-related symptoms, or QoL between patients in the two treatment arms. Fewer inpatient stays for complications were required with GC. CONCLUSIONS: The results of the current study failed to demonstrate any difference in efficacy between the newer regimen of GC and the older regimens of MIC and MVP. Cancer 2003;98:542-53. Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11535

Three hundred patients with symptomatic, locally advanced or metastatic NSCLC not requiring immediate radiotherapy were enrolled into this randomized multicentre trial comparing gemcitabine + BSC vs BSC alone. Patients allocated gemcitabine received 1000 mg/m2on days 1, 8 and 15 of a 28-day cycle, for a maximum of six cycles. The main aim of this trial was to compare patient assessment of a predefined subset of commonly reported symptoms (SS14) from the EORTC QLQ-C30 and LC13 scales. The primary end-points were defined as (1) the percentage change in mean SS14 score between baseline and 2 months and (2) the proportion of patients with a marked (≥ 25%) improvement in SS14 score between baseline and 2 months sustained for ≥4 weeks. The secondary objectives were to compare treatments with respect to overall survival, and multidimensional QL parameters.The treatment groups were balanced with regard to age, gender, Karnofsky performance status (KPS) and disease stage (40% had metastatic disease). The percentage change in mean SS14 score from baseline to 2 months was a 10% decrease (i.e. improvement) for gemcitabine plus BSC and a 1% increase (i.e. deterioration) for BSC alone (P = 0.113, two-sample t -test). A sustained (≥ 4 weeks) improvement (≥25%) on SS14 was recorded in a significantly higher proportion of gemcitabine + BSC patients (22%) than in BSC alone patients (9%) (P = 0.0014, Pearson’s chi-squared test). The QLQ-C30 and L13 subscales showed greater improvement in the gemcitabine plus BSC arm (in 11 domains) than in the BSC arm (one symptom item). There was greater deterioration in the BSC alone arm (six domains/items) than in the gemcitabine + BSC arm (three QL domains). Tumour response occurred in 19% (95% CI 13–27) of gemcitabine patients. There was no difference in overall survival: median 5.7 months (95% CI 4.6–7.6) for gemcitabine + BSC patients and 5.9 months (95% CI 5.0–7.9) (log-rank, P = 0.84) for BSC patients, and 1-year survival was 25% for gemcitabine + BSC and 22% for BSC. Overall, 74 (49%) gemcitabine + BSC patients and 119 (79%) BSC patients received palliative radiotherapy. The median time to radiotherapy was 29 weeks for gemcitabine + BSC patients and 3.8 weeks for BSC. Patients treated with gemcitabine + BSC reported better QL and reduced disease-related symptoms compared with those receiving BSC alone. These improvements in patient-assessed QL were significant in magnitude and were sustained. © 2000 Cancer Research Campaign

The effectiveness of a single 8-Gy fraction prophylactic cranial irradiation regime was assessed in 106 patients with small-cell carcinoma of the lung. All patients had limited stage disease and received combination chemotherapy consisting of either cisplatin or carboplatin with ifosfamide, etoposide, and vincristine (VICE). Cranial irradiation was administered 48 h after the first cycle of chemotherapy and was well tolerated. Actual 2-year survival was 35% and cranial relapse occurred in 22% of those patients who achieved complete remission. This compares favourably with a cranial relapse rate of 45% incomplete remitters previously reported with the same chemotherapy regime after a minimum follow-up of 2 years where PCI was not used. Formal psychometric testing was performed retrospectively on a series of 25 long-term survivors of whom 14 were taken from this reported series. Whilst 75% of patients were impaired on at least one test with 68% performing badly in the most complex task, this was not associated with clinically detectable neurological damage and the patients did not complain of memory or concentration difficulties. In conclusion, single fraction PCI, when used with platinum based combination chemotherapy, appears to be equally effective but may be less neurotoxic than the more standard fractionated regimes.

The need to include simple laboratory indices and performance status evaluation in treatment decision making has been shown by multivariate analyses. The conventional limited-stage extensive-stage division of prognostic groups no longer provides sufficient information. Indeed, some patients in the limited-stage group have a poor prognosis and about one quarter of patients in the extensive-stage group have a better prognosis when information from performance status and pretreatment biochemistry is taken into account. There is no rational clinical need for elaborate staging procedures, eg, computed tomography scanning or bone marrow examination, in the majority of patients with small cell lung cancer. Adequate information for defining prognostic groups can be obtained by using performance status, lactate dehydrogenase, and other biochemical tests such as sodium, alkaline phosphatase, and albumin. Thereby the cost to the patient of unnecessary burdensome investigations and to health care could both be reduced.

Despite its effectiveness in reducing the rate of brain metastases, the role of prophylactic cranial irradiation (PCI) in the management of small cell lung cancer (SCLC) remains controversial because of concern about radiation-induced neurological morbidity. In order to evaluate morbidity and its impact on quality of life 64 patients surviving ≥2 years in remission were recalled for assessment. 52 had received PCI. Most of the patients were well: 95% had performance status ≤1 and nine out of 37 neurological examinations were abnormal. On neuropsychometric testing, only 19% of patients performed at the level expected for their age and intellectual ability on all four tests used. Fifty-four per cent of patients were impaired on two or more of the tests, suggesting a significant degree of measurable cognitive dysfunction. The number of patients who had not received PCI was insufficient for comparative analysis with the number who had, but among those treated with PCI, patients receiving 8 Gy in 1 fraction appeared less impaired than those receiving higher radiation doses in multiple fractions. The study showed that neuropsychometric testing is acceptable to patients, can be administered by non-psychologists in the clinic and is sensitive to otherwise undetected deficits of cognitive function in this patient population. Prospective evaluation of PCI should include neuropsychometric testing.

BACKGROUND: The role of chemotherapy for advanced NSCLC patients and ECOG PS2 remains controversial. We evaluated 4 doses of 3-weekly docetaxel to identify a less toxic, clinically effective dose. METHODS: Seventy-three patients with stage III (22%) (unsuitable for radical surgery/radiotherapy) and IV (78%) NSCLC were randomized to receive 4 doses of 3-weekly docetaxel, for 4 cycles: arm (A) 40 mg/m(2) (n=17), arm (B) 50 mg/m(2) (n=17), arm (C) 60 mg/m(2) (n=19), arm (D) 50 mg/m(2) escalated by 10 mg/m(2) to a maximum of 70 mg/m(2) (n=19). Primary endpoints: maximum tolerated dose, RR, duration of response, symptom improvement, toxicity and QoL. Secondary endpoint: overall survival (OS). Patients and disease characteristics were well balanced. Median age was 67 (range 45-81), there were 32 male and 41 female, histology subtype: squamous/adenocarcinoma/mixed/NOS=42%/49%/4%/5%. RESULTS: Seven patients did not receive any treatment because of deterioration in PS or death. 50% of patients in arm D, who received more than one cycle, received dose escalation. There was no statistical difference in the number of cycles administered (arms A, B and D: median 2 cycles and arm C: median 3 cycles) and no difference in RR: arm A=6%, arm B=6%, arm C=10%, and arm D=0%. There was no statistically significant difference in grade 3/4 neutropenia and thrombocytopenia between the four arms. No difference was observed in hospitalization rate, blood transfusions, antibiotics administration and non-haematological toxicity. QoL: no difference in total scores between baseline and cycles 1-4. There was a significant decrease in pain scores from baseline to post cycles 2 and 3 (p=0.025 and p=0.002, respectively). There was no difference in OS (p=0.992). Median survival and 6-month survival were 61, 86, 88 and 97 days and 29%, 33%, 21% and 26% for arms A, B, C, and D, respectively. CONCLUSIONS: Clinical efficacy of docetaxel was observed at all dose levels. Higher dose levels were not associated with increased toxicities, use of IV antibiotics or hospitalization rates. However, the median survival observed is shorter than historical data and do not support further evaluation of these doses of single agent docetaxel in this population.

167 Thoracic radiotherapy in extensive stage small cell lung cancer M.A. Harris1 *, P. Holland2, R. Hogley2, P.A. Burt3, C. Faivre-Finn3, N. Bayman3, L. Pemberton3, L.W. Lee3, J.H. Coote3, H.Y. Sheikh3, A.Z. Chittalia4, F. Blackhall5, R. Califano5, Y. Summers5, P. Taylor5. 1Clinical Oncology, The Christie Hospital, Manchester, United Kingdom, 2Medical School, Manchester University, Manchester, United Kingdom, 3Department of Radiation Related Research, The Christie NHS Foundation Trust, Manchester, United Kingdom, 4Medicine, University of Manchester, Manchester, United Kingdom, 5Medical Oncology, The Christie Hospital, Manchester, United Kingdom

The aim of this study was to investigate and, if possible, compensate for the effect of intravenous contrast‐enhanced CT scans on the treatment planning dose distributions for lung patients. The contrast and noncontrast CT scans of 3 patients were registered, and the effect of contrast on the Hounsfield units (HU) was assessed. The effect of contrast was then simulated in the CT scans of 18 patients receiving radiotherapy of the lung by modification of the CT numbers for relevant sections of noncontrast‐enhanced CT scans. All treatment planning was performed on the Pinnacle 3 planning system. The dose distributions computed from simulated contrast CT scans were compared to the original dose distributions by comparison of the monitor units (MUs) for each beam in the treatment plan required to deliver the prescribed dose to the isocenter as well as a comparison of the total MUs for each patient, a percentage change in required MUs being equivalent to a percentage change in the dose. A correction strategy to enable the use of contrast‐enhanced CT scans in treatment planning was developed, and the feasibility of applying the strategy was investigated by calculating dose distributions for both the original and simulated contrast CT scans. A mean increase in the overall patient MUs of 1.0 ± 0.8% was found, with a maximum increase of 3.3% when contrast was simulated on the original CT scans. The simulated contrast scans confirmed that the use of contrast‐enhanced CT scans for routine treatment planning would result in a systematic change in the dose delivered to the isocenter. The devised correction strategy had no clinically relevant effect on the dose distribution for the original CT scans. The application of the correction strategy to the simulated contrast CT scans led to a reduction of the mean difference in the overall MUs to 0.1 ± 0.2% compared to the original scan, demonstrating that the effect of contrast was eliminated with the correction strategy. This work has highlighted the problems associated with using contrast‐enhanced CT scans in heterogeneity corrected dose computation. Contrast visible in the CT scan is transient and should not be accounted for in the treatment plan. A correction strategy has been developed that minimizes the effect of intravenous contrast while having no clinical effect on noncontrast CT scans. The correction strategy allows the use of contrast without detriment to the treatment plan. PACS number: 87.53.Tf

PurposeThis randomized phase II study compared two treatment schedules of gemcitabine in patients with non–small-cell lung cancer (NSCLC) and impaired Karnofsky performance status (KP). Primary objectives were to record changes from baseline KP and to assess symptom palliation. Secondary objectives were overall survival, tumor response, and toxicity.Patients and MethodsPatients with stage IIIb and IV NSCLC and KP ≤ 70 were randomly assigned to receive gemcitabine 1,000 mg/m2on days 1, 8, and 15 of each 28-day cycle (3w4) or gemcitabine 1,500 mg/m2on days 1 and 8 of each 21-day cycle (2w3), both for up to six cycles. KP, toxicity, and SS14 lung cancer specific questions were recorded before each cycle of treatment. Response was evaluated 4 weeks after the last cycle.ResultsOne hundred seventy-four patients were enrolled. There was significant early attrition due to disease progression; only 61.5% of patients were alive at 2 months. There was a significant improvement in KP from baseline to pre–cycle 3 in both arms, with a trend in favor of the 3w4 regimen for duration and faster onset of improvement. Eight of the 17 quality-of-life (QOL) variables assessed showed an improvement of more than 10% between baseline and the start of the third cycle of treatment. Response rate, survival, and duration were similar in both arms.ConclusionThere was no significant difference between the two schedules examined in terms of improvement in KP or QOL, but there seemed to be a trend in favor of the 3w4 schedule.

Trastuzumab is an effective treatment for patients with metastatic breast cancer (MBC) that overexpresses HER-2. A high incidence of brain metastases (BM) has been noted in patients receiving trastuzumab. A retrospective chart review was conducted of 100 patients commencing trastuzumab for metastatic breast cancer from July 1999 to December 2002, at the Christie Hospital. Seven patients were excluded; five patients developed central nervous system metastases prior to starting trastuzumab, and inadequate data were available for two. Out of the remaining 93 patients, 23 (25%) have developed BM to date. In all, 46 patients have died, and of these 18 (39%) have been diagnosed with BM prior to death. Of the 23 patients developing BM, 18 (78%) were hormone receptor negative and 18 (78%) had visceral disease. Univariate analysis showed a significant association between the development of cerebral disease and both hormone receptor status and the presence of visceral disease. In conclusion, a high proportion of patients with MBC treated with trastuzumab develop symptomatic cerebral metastases. HER-2-positive breast cancer may have a predilection for the brain, or trastuzumab therapy may change the disease pattern by prolonging survival. New strategies to address this problem require investigation in this group of patients.

Megavoltage imaging (MVI) has been used to obtain digital images of treatment fields during therapy for non-small cell lung cancer. Tumours were seen in all 33 cases studied and in three cases MVI was used to improve the set-up. It is concluded that in the setting of radical radiotherapy for non-small cell lung cancer this is an appropriate technique for the verification and correction of field position and is an aid to quality assurance.

Methods: Patients with non-small cell lung cancer treated with 36Gy in 12 fractions over the last 2 and half years were identified via the Varian patient manager treatment system. Demographic, histopathological, clinical and toxicity data were collected from patient records and hospital IT systems. Data were anonymised and analysed by the authors. Results: The total number (N) of patients available for analysis was 56. The results are summarised in the table. The median age of patients at the start of treatment was 70 years (range 37 85 years). Post-radiotherapy haemoptysis was reported in 3 patients (5.1%). No patient developed myelopathy. The commonest described toxicity was dysphagia, but only 3 (6.9%) developed grade 3 dysphagia. Most patients were treated with radiotherapy via an AP-PA parallel opposed pair, median field size was 120.96 cm2 (range 75.5 209.33 cm2), consistent with the comparator where field size did not normally exceed 200 cm2. Conclusions: High dose palliative radiotherapy in Oxford University’s NHS Trust is safe and tolerable with no radiation induced myelopathy. The main toxicity of dysphagia is generally non-severe. The median survival of patients is comparable to the 9 month survival seen in the 13 fraction arm of the MRC Trial, indicating a genuine application to everyday radiotherapy practice.

BACKGROUND Information on the effect of chemotherapy in a group of patients with poor prognosis, poor performance status small cell lung carcinoma (SCLC) is scarce. A randomized study comparing single-agent carboplatin with combination chemotherapy in this largely unreported population of SCLC patients was undertaken. METHODS One hundred nineteen patients were allocated to four cycles of either cyclophosphamide, doxorubicin, and vincristine (CAV) or single-agent carboplatin. Patients had either a Karnofsky performance score ≤ 50 and/or a prognostic score indicative of a 1-year survival rate ≤ 15%. RESULTS Grade 3–4 neutropenia and intravenous antibiotic use were significantly more common with the CAV regimen (P < 0.005). Conversely, Grade 3–4 thrombocytopenia was more common (P < 0.0009) and platelet transfusion was more frequent (P < 0.05) with carboplatin therapy. Nonhematologic toxicity was similar in both treatment arms, except for alopecia with CAV therapy (P < 0.0007). Symptom relief occurred in 48% and 41% of patients in the CAV and carboplatin treatment arms, respectively. Dyspnea was improved in 66% and 41% of patients and cough was improved in 21% and 7% of patients in the CAV and carboplatin treatment arms, respectively. CAV therapy produced a higher response rate than carboplatin (38% vs. 25%), but this was not statistically significant (P = 0.15). The median overall survival for patients in the CAV and carboplatin treatment arms was 17 weeks and 15.9 weeks, respectively, with 1-year survival rates of 12% and 6%. CONCLUSIONS Single-agent carboplatin is a feasible treatment in patients with poor prognosis SCLC and produces response rates, relief of tumor-related symptoms, and survival similar to what is seen in patients who receive CAV chemotherapy. The lower risk of life-threatening sepsis and less need for hospitalization or intravenous antibiotic courses is advantageous in this susceptible patient population. Cancer 2001;92:601–8. © 2001 American Cancer Society.

Background and purpose : Despite advances in operative and postoperative care, long term survival rates following radical oesophagectomy are poor. Surgery remains the mainstay of radical treatment despite various series reporting similar results for treatment with radiotherapy, in particular in the upper third of the oesophagus. We have studied a cohort of patients treated with definitive radiotherapy to examine the influence on survival of changes in diagnostic scanning and radiotherapy computer planning as well as various patient and disease related prognostic factors. Patients and methods : From 1985 to 1994, 101 patients with clinically localised carcinoma of the oesophagus were treated at the Christie Hospital with definitive radiotherapy. This included 11 patients with oesophageal adenocarcinoma. Diagnostic and planning techniques changed over the period studied, with increasing use of both diagnostic and radiotherapy planning CT scanning. Radiotherapy doses ranged from 45 to 52.5 Gy in 15 or 16 fractions over 3 weeks. Results : The 3- and 5-year survival figures were 27% and 21%, respectively, corrected for intercurrent deaths. Survival was better for adenocarcinoma than squamous cell carcinoma, though not statistically significantly. The only significant prognostic factor ( P =0.01) was the use of diagnostic CT scanning (42% versus 13% 5-year survival with or without diagnostic CT scanning, respectively) which was associated with an increase in field size. Radiotherapy was well tolerated with no acute mortality or significant morbidity. Late stenosis requiring oesophageal was seen in five of 20 patients surviving 3 years or more. Conclusions : Survival following well planned radiotherapy is an effective alternative to surgery for both squamous cell and adenocarcinoma. Advances in staging and three-dimensional planning and the use of multimodality treatment may further improve survival.

Growing hair follicles with their rapid cell proliferation would be expected to be sensitive organs to cytotoxic agents such as radiation. Various abnormalities in the hair and hair follicles have been reported in the past. Changes in the number of cells in the newly forming hair cortex have been shown in the mouse to be one of the more sensitive assays for radiation effects, and this approach could provide a basis for a biological dosimeter. Here we show for the first time using hair cortex cell counts some preliminary data indicating that the number of cell nuclei in a unit of length (140 microns) of the cortex of human hairs from the chest and scalp of patients undergoing fractionated radiotherapy falls significantly (P = 0.005) by 5%-10% 3 days after the first dose in a fractionated sequence of irradiations. The first dose was delivered on a Friday, and no further exposures were delivered until after the hair sample was taken on the 3rd day (Monday). No significant effect of radiation dose could be detected over the available. limited range of doses studied (5-6.5 Gy with one exit dose sample at 2.6 Gy). Also, the width varies from hair to hair. If the width of the hair is taken into account and the cortical nuclei counts are normalised to the width of each hair, the effects seen at day 3 become slightly more significant (P = 0.002), and those at day 5 also become significant (P = 0.012). Samples taken on the 5th day after the first (Friday) exposure were also 2 days after the second exposure and 1 day after the third exposure. However, little expression of damage attributable to the 2nd and 3rd exposures was anticipated since their effects would take some time to be expressed in the cortical region examined, which is some distance from the proliferative region of the follicle.

Between April 1988 and December 1992, 37 patients with small, previously unirradiated, primary non-small cell carcinomas of the bronchus causing symptoms due to endobronchial disease were treated at the Christie Hospital, Manchester, with a single fraction of high dose rate intraluminal radiotherapy (ILT) using the microSelectron-HDR machine. Small primary (SP) lesions were defined as being less than 2 cm in diameter in a direction perpendicular to the central axis of the iridium-192 treatment source. Fifteen patients (41%) were treated to a dose of 15 Gy and 22 patients (59%) to 20 Gy at a distance of 1 cm from the central axis of the source. At 6 weeks following ILT, improvement in symptoms was seen in the following percentages of patients: haemoptysis 96%, pulmonary collapse 69%, cough 55% and dyspnoea 52%. The magnitude of improvement in these symptoms was largely maintained in patients surviving to 4 months and then 12 months post-ILT. Median actuarial survival was 709 days, 2-year survival 49.4% and 5-year survival 14.1%. Overall, there was no significant difference in survival after treatment with 20 Gy compared with 15 Gy at 1 cm. At the close of study, there were four patients still alive without disease recurrence with survivals of 38, 48, 49 and 63 months. All had had biopsy-proven squamous cell carcinomas and all had been treated with 20 Gy at 1 cm. Five patients died from massive haemoptysis as a terminal event at 4, 9, 9, 10 and 11 months post-ILT, well below the median survival for this group of patients. Again, all had been treated with 20 Gy as opposed to 15 Gy at 1 cm. Over the same time period, 287 patients with non-small cell carcinomas of more than 2 cm in diameter (large primary lesions, LP), were treated with a single fraction of ILT only, as their initial treatment. A consistently greater percentage of patients with SP lesions showed an improvement in the symptoms of haemoptysis and pulmonary collapse when compared with patients with LP lesions. Patients with LP lesions demonstrated a decreased actuarial survival when compared with SP lesions, with median survival being 156 days, 2-year survival 3.1% and no survivors beyond 39 months. This study demonstrates that, in patients with small endobronchial carcinomas a single fraction of ILT can give efficient palliation of symptoms and lead to long term disease-free survival, but that a dose of 20 Gy may be at the limit of bronchial radiation tolerance for a single dose technique employing a high dose rate source.

Purpose: The aims of the work were to study the intrinsic radiosensitivity of tumor biopsies from patients with cervical carcinoma and to correlate the data with information on patient age, disease stage, differentiation status, tumor volume, and tumor ploidy. Methods and materials: Radiosensitivity was assessed for 145 tumors in vitro as surviving fraction at 2 Gy (SF 2 ) using a clonogenic assay. Results: Although the clonogens in tumors classified as Stage I or II tended to be more radiosensitive than in Stage III or IV disease, the difference was not statistically significant ( p > 0.15). There was also no significant difference in the intrinsic radiosensitivity of well, moderately, or poorly differentiated tumors or between squamous cell carcinoma and adenocarcinoma ( p > 0.53). There was no correlation between patient age and tumor radiosensitivity ( p = 0.49). Large volume (≥ 4 cm) disease was more radioresistant than small volume ( p = 0.08). Finally, diploid tumors tended to be more radioresistant than aneuploid tumors ( p = 0.07). Conclusion: The intrinsic radiosensitivity of cervix tumors is independent of disease stage, tumor grade, and patient age. Weak trends, however, were observed of increased tumor radioresistance for large volume disease and diploid tumors, suggesting that tumor SF 2 may not be a completely independent parameter.

A total of 197 patients, who presented to the Christie Hospital with advanced carcinoma of the oesophagus, were treated with the high dose rate microSelectron between June 1988 and June 1992. In 54%, a single intraluminal brachytherapy treatment resulted in useful palliation, which was sustained for a substantial part of the patient's remaining life. The simplicity of the treatment, which could be completed as a day case procedure and did not cause significant morbidity, commends itself in the palliation of these patients who have poor overall survival and quality of life. Approaches that might improve the response rate in those patients who did not gain significant palliation after a single treatment are discussed.

e18095 Background: The presence of Epidermal Growth Factor Receptor (EGFR) activating mutations in patients with NSCLC was first described in 2005. Tumours exhibiting these mutations show sensitivity to treatment with an oral Tyrosine Kinase Inhibitor. Testing for EGFR mutations in patients with non-squamous NSCLC began in the Greater Manchester and Cheshire network in the last quarter of 2009. Methods: We audited the notes of consecutive patients who were identified with an activating EGFR mutation by the Central Manchester Genetics Laboratory between November 2009 and October 2011. Results: A total of 110 mutations were identified in tumour tissue from 98 patients. 13.6% were in exon 18, 38.2% in exon 19, 15.4% in exon 20 and 32.8% in exon 21. 65% of patients were female. The median age was 69 years (36-89). Notes were available for 85 patients, 59 of whom received treatment with an EGFR TKi. 7 had previously received radical treatment and 19 never received treatment. 7% were current smokers, 40% were ex-smokers, 30.6% had never smoked and smoking history was not documented in 22.4%. An initial response to treatment was seen in 55%, with stable disease in 15%.The mean duration of treatment was 7.6 months (2 weeks – 23 months), with 24 patients still receiving a TKi at the time of data analysis. The most commonly seen toxicities were diarrhoea and rash. Only 1 patient had no documented toxicity from their TKi. 17 patients (29%) had treatment discontinued or interrupted because of toxicity. In 8 of these, treatment was re-introduced at a reduced dose, and 3 patients went back to full dose. Conclusions: Our results confirm that treatment with a TKi is effective for those patients whose tumours harbour EGFR mutations, with a side effect profile consistent with published data.

In April 1988 the Christie Hospital started using the microSelectron-HDR machine to deliver intraluminal radiotherapy (ILT) to inoperable bronchial carcinomas causing symptoms due to endobronchial disease. Results of treatment in the first 406 patients with primary non-small-cell carcinoma are presented. Three main categories of patient were defined. Category 1 consisted of 324 patients (79.8%) who were previously unirradiated and received a single fraction of ILT as their primary treatment, mostly to a dose of 1500 cGy (76%) or 2000 cGy (23%) at 1 cm from the centre of the iridium-192 treatment source. The percentage of these patients whose symptoms or signs were improved at 6 weeks following ILT were as follows: stridor 92%, haemoptysis 88%, cough 62%, dyspnoea, 60%, pain, 50% and pulmonary collapse, 46%. Approximately two-thirds of these patients (67.3%) derived long lasting palliation and required no further treatment during their lifetime. The other third of patients needed subsequent treatment at some stage because of recurrence of their symptoms and in this situation external beam radiotherapy (EB) or a repeat ILT treatment was effectively utilised. Category 2 consisted of 65 patients (16%) who had previously received EB but required ILT when their tumour recurred. At 6 weeks post-ILT levels of symptom palliation were broadly similar to those obtained if ILT was used in previously unirradiated individuals, although the improvement was not so well sustained with time and only 7% showed improvement in pulmonary collapse at 6 weeks. Category 3 consisted of 17 patients (4.2%) in whom ILT was used concurrently with EB as a combined initial treatment. Similar levels of palliation were seen when compared with patients who received a single ILT treatment only. Overall, ILT was well tolerated in terms of early and late morbidity. In conclusion, the efficiency of a single ILT treatment in palliating symptoms due to endobronchial tumour in previously unirradiated individuals is comparable with that reported in series where treatment for advanced lung cancer combines a prolonged course of EB concurrently with several ILT treatments.