Analysis of the motion of lung tumor using fluoroscopy

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~ - - ~ Radiotherapy treatment delays and lung cancer progression N. O'Rourkc 1, F. Milne I , R. Edwards 2, 1Beatson Oncology Centre,

Glasgow; 2Radiology Dept. Gartnavel Can. Hosp., Glasgow, UK Introduction: Increasing demand for treatment and chronic underprovision of radiotherapy facilities in the UK has led to long waiting lists for radiotherapy treatment. Patients with NSCLC awaiting radical radiotherapy are particularly at risk of tumour progression given the natural history of this disease. Method: In 1999 29 patients were assessed by NOR and booked for radical radiotherapy for NSCLC. We are now auditing the treatment delays for each patient and comparing this with the national (RCR) guidelines on maximum recommended waiting times. For each patient we have recorded pathology, stage of disease, number of days between first attendance at hospital and commencing treatment and number of days between diagnostic CT scan and planning scan for radiotherapy treatment. We are measuring tumour size on diagnostic CT and comparing this with tumour size at time of planning CT to assess tumour progression. Results: 21 men and 8 women aged 45-83 (median 67) were booked for treatment. 20 had squamous carcinoma, 7 adenocarcinoma, 1 unspecified NSCLC and 1 had no pathology. 8 patients had Stage I disease. 6 stage II and 15 stage Ill. Of the 29 patients, 6 (21%) did not make it to radical treatment: 1 died while on the waiting list, 1 had progression of symptoms requiring urgent palliation and a further 4 had planning CTs which showed tumour progression beyond a size where radical radiotherapy was feasible. The delay between diagnostic and planning CT was 18-131 days (median 54) with only 3 patients (11%) planned in under 28 days and 7 (25%) had a delay of more than 12 weeks. The delay between first clinic visit and starting treatment was 35-187 days (median 96) with only 2 patients (7%) treated within 6 weeks and 10 (36%) waiting more than 16 weeks. Assessment of tumour sizes on scans will be complete by Feb 2000. Conclusion: The West of Scotland has an incidence of NSCLC that is among the highest in the world and has one of the lowest survival rates. Our results show that even in the small proportion of patients who are candidates for radical radiotherapy, the limitations of the service and the resources can prevent patients from receiving curative treatment and even for those who do receive it, there is likely to be tumour progression on the waiting list. rationale for curative radiotherapy schemes in [5-33-] Dosimetric occult lung carcinoma F.J. Lagerwaard, L.H. Mutter, J.A. Burgers, C. de Pan, P.C.M. Koper, S. Senan. University Hospital Rotterdam, Rotterdam, The Netherlands

Background: Endobronchial brachytherapy (EB) is a curative treatment for radiologically occult bronchial carcinoma. However, major complications such as fatal haemoptysis and bronchial wall necrosis, have been reported in more than 16% of patients following EB alone, and the complete response rates at 1 year were only 75% (Pero11997). Three-dimensional treatment planning can improve the therapeutic ratio of EB (Senan, in press). We recently described different tools for assessment of 3D dosimetry, including dose volume histograms (DVH) (Lagerwaard, in press). As the risk of peribronchial tumor extension and/or nodal involvement increases in occult carcinomas measuring >1 cm on bronchoscopy (Usuda 1993), the clinical target volume (CTV) for such tumors should encompass the bronchial wall and adjacent peribronchial space. Attempting such target coverage with EB alone can lead to 'hot spots' in critical normal tissues, and it was recommended that combined EB and external radiotherapy (ERT) be performed for lesions > 1 cm (Speiser 1997). Aim: To perform a dosimetric analysis using the serial planning CTscans of a patient who developed a local recurrence after EB alone for an occult non-small cell lung carcinoma. Methods: EB (5 x 8 Gy) was performed in a patient with a tumor extending from the distal left main stem bronchus through the carina of the left upper (LUB) and lower lobe (LLB) bronchus. Only

a single applicator (in the LLB) could be placed for the first two treatments. Subsequent tumor regression allowed two applicators (in LUB and LLB, respectively) for the last three fractions. CT scans were performed during 4 fractions. A local recurrence occurred in the proximal LUB eight months later. Dosimetric analysis was performed using a brachytherapy planning system (PLATO, BPS v 13.3) and the DVHs were compared to those obtained using simulated ERT (50 Gy) combined with EB (2 x 6 Gy) to the same CTV, which was defined as the involved airways and adjacent peribronchial tissue. Results: Cumulative DVHs from the actual EB procedures showed poor CTV coverage. The use of 2 applicators also did not result in adequate CTV coverage. In contrast, combined ERT and EB achieved superior target coverage and minimized 'hot spots'. Conclusion: Local failure after EB alone can be explained by inadequate target coverage, which is inherent to the rapid dose fall-off in EB. DVH analysis indicates that combined ERT and EB provides for improved coverage of the CTV for occult lesions > 1 cm.

I-5-~ Prediction of the effect of fracUonated irradiation in vitro and in vivo in human lungcancer O. Brodin, M. Bergqvist, D. Brattstromm, G. Wagenius. Oncology,

South Hospital, Stockholm; Oncology, University Hospital, Uppsala, Sweden Radiotherapy has a poor effect in NSCLC but is limited also in SCLC. Is it possible to improve the effect? A radiobiological model predicting the effect of fractionated radiotherapy has been applied in 5 human lung cancer cell lines IN VITRO. The model includes surviving fraction (SF) after single dose irradiation, doubling time and the number of tumour cells before the start of the treatment. Three of the cell lines were very or moderately radioresponsive (SF2 Gy 0.25-0.60 and in these cell lines the prediction was excellent if exponential growth of 2.5 days was applied. However in the 2 radioresistant call-lines (SF2Gy 0.900.95) predicition was better if no proliferation was applied. This might be due to the low cell-kill in the resistant cell-lines, very soon making the culture dishes overcrowded not permitting survival. Our conclusion is that the model seems valid for prediction of survival after fractionated irradiation IN VITRO. The model might also be applied clinically. Using the proliferation rate and range of SF's found in human SCLC and NSCL cell lines on clinical materials, indicates that hyperfractionated, accelerated treatment should be better than treatment once a day. This is in accordance with clinical results. Further analysis also indicates that low control rates, similar to what is found from radiotherapy in NSCLC from radiotherapy is predicted. The better results in SCLC is also predicted by the model. Our conclusion is that this model might be useful for the optimisation of fractionated radiotherapy under the assumption that clinically useful methods for the evaluation of SF and proliferation rate in individual tumours was accessible. I-5--~ Analysis of the motion of lung tumor using fluoroscopy K.H. Shin, E.K. Choi, W.K. Chung, B.Y. Yi, K.J. Kim, Y.J. Nho, S.D. Ahn, J.H. Kim, H.S. Chang. Dept. of Radiation Oncology, Asan

Medical Center, College of Medicine, University of UIsan, Seoul, Korea This study was designed 1) to measure the motion of lung neoplasm by lobar location of tumor objectively, 2) to evaluate the factors affecting tumor motion, and 3) to determine the optimal margins of planning target volume (PTV) for 2, 3 dimensional radiation therapy or whole body radiosurgery. Tumor motions of 15 patients with lung neoplasms were evaluated with fluoroscopy at the first time of simulation. Anteriorposterior (AP) and lateral dynamic images were recorded by video tape recorder connected with fluoroscopy. After sending these images to a personal computer, the uppermost and lowermost static images were captured with image-editing software program and motions were measured in the direction of AP, superior-inferior (SI) and right-left (RL). The average SI motion was the longest (0.82 cm), followed by RL (0.32 cm) and AP (0.22 cm). Tumors located in right and left lower

Radiation lobes showed (RL, SI, AP) motions of (0.53, 1.59, 0.41 cm) and (0.68, 1.43, 0.57 cm), respectively and were greater than tumors in right upper (0.23, 0.38, 0.15 cm) and left upper (0.17, 0.40, 0.11 cm) lobes. Right middle lobe tumor revealed nearly the same SI motion with those of both lower lobes, while RL and AP motions were alike to both upper lobe tumors (0.30, 1.38, 0.17 cm). Tumor motions of T4 stage (N = 7: 0.24, 0.42, 0.20 cm) were less than those of T1 (N = 2: 0.43, 1.50, 0.40 cm) and T2 (N = 6: 0.37, 1.07, 0.20). Both the physical factors of movements of diaphragm, heart and aorta according to cardiac and respiratory motion and tumor factors of tumor size, T stage seem to influence tumor motion. We measured tumor motion objectively, and recommend that this analysis be used guidelines of the optimal margins for the determination of PTV during radiotherapy. The optimal margins should be different by lobar locations of tumor.

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the total PCI dose when 4 dose groups (8 Gy, 24-25 Gy, 30 Gy, 36-40 Gy) were analyzed, [trend p = 0.02], but the effect on survival did not differ significantly according to the dose. The 2-year BM incidence was 39% in the 24-25 Gy group and 21% in the 36-40 Gy group. Based on these results, a tdal comparing a standard PCI dose (25 Gy/10 F/12 d) to a higher dose of conventional radiotherapy (RT) (36 Gy in 18 fractions and 24 days) or accelerated hyperfractionated RT (36 Gy in 24 fractions and 16 days) has been initiated in limited SCLC with CR. Each center chooses one of the high dose RT options. The main endpoint is brain metastasis rate at 2-years. Quality of life, late sequelae and survival will be also evaluated. With widespread collaboration, it will be possible to include the 700 patients needed in 3 years. The trial has been activated in September 1999, and 61 centers throughout 24 countries have joined.

~-3-~ Modifications of the TNM Staging System for Lung Cancer Patients Undergoing Non-Surgical Therapy H. Wagner. H. Lee Moffitt Cancer Center, Tampa, FL, USA The TNM staging system as presently used for non-small cell (NSCLC) but not small cell (SCLC) lung cancer was based largely on data of patients receiving primary surgical treatment. As such, it has shown reasonably good correlation with treatment outcome for patients undergoing resection but its applicability to patients undergoing nonsurgical treatment can be questions. While the ability of the surgeon to obtain histologically negative margins plays a major role in determining resectability, issues of tumor volume are now well incorporated in the current system but are highly important in determining disease control with radiation therapy and chemotherapy. The widespread availability and use of three dimensional tumor reconstruction for radiation therapy planning allows more formal and explicit incorporation of tumor volume in the staging system. Several specific suggestions to consider for modification to the TNM system, both for NSCLC and SCLC, include the following: 1. Explicit inclusion of tumor volume (primary plus macroscopic nodal metastases). It is not uncommon for the total tumor volume in mediastinal nodes to approach or even exceed that in the primary tumor, which is important if one considers strategies of gene therapy or other radiosensitizers targeting only the primary tumor volume. 2. Explicit consideration of post-chemotherapy residual tumor volume as a potential prognostic factor in patients receiving sequential chemoradiation. 3. Distinction between T4 with malignant effusion and T4 with contiguous extension to an unresectable organ. Examples of these considerations and their impact on prognosis will be presented from our institutional database of patients treated by a uniform treatment policy of induction chemotherapy followed by conformal radiation for NSCLC and concurrent chemoradiation for SCLC.

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Why a new Prophylactic Cranial Irradiation (WP) trial in small cell lung cancer (SCLC): From the msta-analysis on PCI in SCLC complete responders to an international trial on PCl dose (PCl99)

C. Le P~choux. For the Prophylactic Crania/Irradiation (PCI99) International Trial Group; Institut Gustave Roussy, 94805, Villejuif, France A recent meta-analysis using individual data from 7 trials including 987 patients compared PCI to no PCI in SCLC in complete responders. The analysis was performed on an intention-to-treat basis and used the Iogrank test adjusted for trials. The PCI dose ranged from 8 Gy in 1 fraction to 40 Gy given in 20 fractions. About half of the patients received 24-25 Gy with doses per fraction ranging from 2 to 3 Gy The relative risk of death in the PCI group compared to the control group was 0.84 (95% CI = 0.73-0.97, p = 0.01), corresponding to a 5.4% increase in favor of PCI in the 3-year survival rate (from 15.3% observed in the control group to 20.7%). PCI significantly increased the brain metastasis-free interval (p < 0.0001 ) and disease-free survival (p < 0.0001) The effect of PCI on brain metastases (BM) increased with

Tuesday, 12 September 2000

4:00-5:00 pm

ORAL SESSION

Radiation

[5-•

Intemational variation in palliative RT regimens for lung cancer: A questionnaire survey

F.R. Macbeth. Velindre Hospital, Cardiff, Wales, UK Rationale: Previous surveys have shown widespread variation in the regimens of palliative radiotherapy used for patients with lung cancer. Eight randomised trials have been published in the past 10 years on the topic and give good evidence on the most effective regimens. This study was devised to assess the impact of these trials on clinical practice. Method: At an international cancer conference (ECCO), held in Vienna in 1999, a systematic review of the eight trials of palliative radiotherapy for lung cancer was presented. A questionnaire was distributed to members of the audience who were invited to answer questions about their treatment of two hypothetical patients - one with symptoms and poor performance status (PS) and one asymptomatic with good PS - and about their willingness to change practice after hearing the evidence presented. Results: 100 questionnaires were distributed and 44 were returned, with respondents from 19 countries in Europe, Middle East, Africa and Australia. For the two cases a total of 27 different radiotherapy regimens were recommended with doses ranging from 8 Gy/1 F to 70 Gy/35 F. The most frequent reason for the choice of regimens (30/44, 68%) was 'departmental policy'. 'Research findings' were mentioned by 12/44 (27%). A minority of respondents (16 for case 1 and 9 for case 2) said that they would change their preferred regimen in the light of the evidence presented. Conclusions: There is still widespread practice variation in the regimens used for palliative radiotherapy for lung cancer and considerable reluctance to change in the light of good research evidence.

[5-•

Uninterrupted twice a day radiation with concomitant chemotherapy in advanced non-small cell lung cancer

J. Pisch, S. Malamud, D. Ross, I. Yudelman, S. Keller. Beth Israel Medical Center, New York, NY 10003, USA Seventy-nine patients with non-small cell lung cancer were treated with concomitant chemo-radiation therapy. Thirty-seven were male and 38 female. All but seven were smokers for at least 25 years. Fifteen patients were ex-smokers of at least one year. TNM staging was as follows: T1-7, T2-18, T3-26, T4-25 patients. There were 55 patients with N2 disease, 13 with N3, 2 had N1, and 6 patients had no enlarged nodes on the CT scan. There were 5 patients with solitary, brain