Radiation therapy for patients with stage III inoperable squamous cell lung carcinoma

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Radiation

there were 3 Iocoregional recurrences after surgery. A 3-D treatment planning system with BEV was used for all patients. Patients underwent limited elective nodal irradiation of 56 Gy. The GTV with 1 cm margin received a dose of at least 70 Gy. Acute and late toxicity were estimated according to the RTOG/EORTC score. Results: The mean follow-up was 217 (80-360) days. Seventeen patients received 74 Gy, two had 72 Gy, and one had 70 Gy. One patient died as a result of radiation pneumonitis. In other patients the acute toxicity was acceptable. Seventeen patients were evaluable for response. There were 3 (18%) complete responses, all in patients staged land II, seven (41%) partial responses, 5 (29%) non-responses and two (12%) local progressions. Two local progressions and two distant failures occurred in stage III patients. Conclusions: Dose escalation > 70 Gy using 3-DCRT in management of NSCLC is feasible with acceptable acute toxicity.

[-56-~ Exclusive radiotherapy for inoperable stage I Non Small Cell Lung Cancer (NSCLC): A multicentric study D. Gouders 1, R Maingon 2, P. Rodrigus 3, B. Hahn 4, M.D. Arnaiz 5, T. Nguyen e, C. Landmann 7, J.E Bosset 8, S. Danhier 1, P. Van Houtte 1. l lnstitut Jules Bordet, Brussels, Belgium, 2Centra Leclerc,

Dijon; elnstitut J. Godinot, Reims; 8CHU Besan~on, France, 3B. Verbeeten Instituut, Tilburg, Netherlands, 4CHU Vaudois, Lausanne; 7Kantonsspital Basel, Basel, Switzerland, 51nstitut Catala d'Oncologia, Barcelona, Spain Radical radiotherapy for NSCLC remains a controversial issue regarding the outcome and the radiation technique. This multicentric study included 87 patients treated in 8 European centers from 1982 till 1994. Criteria of inclusion included a stage I NSCLC, an exclusive irradiation without any chemotherapy except a relapse, no prior cancer neither any endoluminal brachytherapy. Age range was between 56 and 88 years, tumor size from 1 to 10 cm. There was 22 T1N0 and 65 T2N0. Doses varied from 32.5-to 74 Gy and were converted into 2 Gy per fraction schedule: 22 patients received less than 45 Gy and 14 had no mediastinal irradiation. The 2-year survival rates were 26% for the series, 45% for T1 and 20% for T2. Local failure occurred in 27 patients, 5 T1 and 22 T2. A single mediastinal relapse was only seen in 1 patient. Only for T1, doses in excess of 59 Gy decreased the local failure rate: 30% versus 16%. No difference was observed for T2, tumor location or mediastinal irradiation. In conclusion, results remains dismal in this series of stage I NSCLC with a high rate of local failure outlining the necessity to improve the quality of the radiation treatment by increasing the total dose. Tumor size is also an important prognostic factor for radiotherapy

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How reliable are the conclusions from randomieed trials on palliation?: An example from the MRCIBTS LU t7 randomised trial W. Qian, D.J. Girling, M.K.B. Parmar. On Behalf of All Collaborators; MRC Clinical Trials Unit, London, UK

The LU 17 trial was designed to study the role of immediate thoracic radiotherapy (TRT) in preventing or palliating chest symptoms in patients with inoperable non-small cell lung cancer (NSCLC) not suitable for radical TRT with curative intent. Patients were randomised to supportive care plus either immediate TRT (IM), or TRT delayed (D) until needed. The principal outcome measure was defined as alive and without moderate or severe chest symptoms at 6 months. Patients were to be assessed at 1, 2, 4, and 6 months. Between Sept. 1992 and May 1999, 115 patients were randomised into each group. The chi-squared test showed that there was no difference in the prevention of chest symptoms at 6 months at significance level 0.05. However, 12 (10%) of the IM patients received TRT after 4 weeks and 10 received no TRT. 47 (41%) of the D patients received TRT with the median time to start of 3.6 months. In view of the fact that the time to treatment from randornisation was sometimes not very long in the D group and late in the IM group, it is desirable to make comparisons across the

6-month period to assess the robustness of the single 6-month point analysis. However, the numbers of patients assessed in the IM and D groups at 1,2, 4 and 6 months, were 65 (57%) and 93 (81%), 74 (64%) and 67 (58%), 99 (86%) and 95 (83%), and 96 (83%) and 100 (87%), respectively. A large proportion of assessments was missed and it is impossible to recover such missing information. Various approaches should be implemented to assess the reliability of any conclusions. We first compared the prevention of chest symptoms at each assessment time separately. Then a statistical model was applied, in which all assessments were combined and possible influencing factors were incorporated. Both of these more extensive approaches showed no difference in the prevention of chest symptoms. Hence, we believe that the initial conclusion of LU 17 based on a single time point analysis, that immediate palliative TRT in minimally symptomatic patients with locally advanced NSCLC confers no improvement of symptom control compared with TRT on symptomatic progression, is robust and reliable.

l-5-6-2-] Definitive radiation therapy for non-small cell lung cancer directly invading chest wall and vertebral body M. Furuta, M. Nozaki, Y. Murakami, Y. Kitazumi, M. limuro, N. Iwasaki, Y. Hamashima, K. Nagao. Koshigaya Hospital, Dokkyo University

School of Medicine, Koshigaya, Japan Purpose: To clarify clinical usefulness of radiation therapy for nonsmall cell lung cancer (NSCLC) directly invading chest wall (T3 disease) and vertebral body (T4 disease). Patients and Methods: From 1985 to February 1999, 22 patients with NSCLC obviously invading chest wall and spine were treated mainly with definitive radiation therapy. Median age was 70 (range 47-83 years), and performance status (0/11213) was 01111714. Adenocarcinoma was present in 10 patients, squamous cell ca. in 7, and others in 5. Eleven patients had clinical T3N0 disease, four T3N2, one T3N3, five T4N0, and one T4N3. Tumor invasion to the rib/vertebral body was diagnosed by obvious bone destruction on chest radiograph/CT. Intercostal muscle involvement was diagnosed by tumor invasion more than 1 cm outwards from the pleural plane on CT. Chest wall (muscle/rib/both) and vertebral body invasion were noted in 15 (3/4/8) and 7 patients. Median tumor size was 7.0 cm (range 4.3-11.5 cm) for chest wall involvement, while 5.0 cm (3.2-8.0 cm) for vertebral invasion (p < 0.011). No statistical differences in age, PS, histology, nodal involvement, and total dose of radiotherapy were noted between the two groups. All patients suffered from pain due to local tumor invasion before the treatment. Results: Pain was reduced in all patients, and administration of analgesic was discontinued in 8 patients (53%) with chest wall invasion and in 4 patients (57%) with vertebral invasion (n.s.). Initial response of tumor to the treatment (CR/PPJNC/PD) was 1171710for chest wall disease and 1111510for vertebral disease (n.s.). Two-year local control rate including 7 cases lost for follow-up was 34% for chest wall disease and 64% for vertebral disease (n.s.), and the 2-year overall survival rate was 21% and 46%, respectively (n.s.). Median time of local control was 6 months for patients with chest wall involvement, and 11 months for vertebral invasion. Two of 7 patients with vertebral involvement survived over three years without recurrence. Conclusions: Improved QOL is expected by radiation therapy in patients.with NSCLC directly invading chest wall and vertebral body. No better local control of the disease was observed in patients with chest wall involvement (T3 disease) compared to those with vertebral involvement (T4 disease).

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Radiation therapy for patients with stage III inoperable squamous cell lung carcinoma

Y. Nakayama, K. Hayakawa, M Furuta, N. Mitsuhashi, H. Niibe.

Gunma University Maebashi, Japan Purpose: To evaluate the role of radiation therapy (RT), we analyzed the prognostic factors of the patients with stage III squamous cell carcinoma (SCC) treated with definitive RT.

Radiation Materials and Methods: From 1976 through 1994, a total of 113 patients with stage III SCC without malignant effusion were treated with definitive RT in our clinic. All patients were treated with 10 MV x-rays using antero-posterior parallel opposed fields. The total dose ranged from 60 Gy to 80 Gy with 2-Gy once daily standard fractionation. Results: The actuarial two and five-year survival rates of the entire group were 28% and 18% respectively with a median survival time (MST) of 12 months. There were no significant differences in survival based on substage (Ilia vs IIIb), age and sex. However, there was a borderline difference in survival rates between 29 patients with tumor size smaller than 5 cm and 84 patients with tumor size over 5 cm (P = 0.06). No patients with involvement of subcarinal node were alive beyond 4 years. In t9 patients with N2 stage among 29 patients with tumor size smaller than 5 cm, the two and five-year survival rate of 12 patients without involvement of subcarinal lymph node were 75% and 47%. There was a statistically significant difference in survival between patients with and without subcarinal involvement (P = 0.03). Conclusion: In stage III SCC patients, the patients with tumor size smaller than 5 cm without involvement of subcarinal lymph node are good candidates for definitive RT. of Care Study of radiation therapy for lung cancer [56• inPatterns japan: The influence of the stratification of institution

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lead to increase lung toxicity. To reduce lung toxicity, in addition to shrinking field technique, we used thoracic irradiation encompassing post induction chemotherapy tumor volumes, that should allow for a marked decrease in the amount of normal lung irradiated compared with thoracic irradion including the prechemotherapy tumor volume. Between Feburery 1989 and Feburary 1999, thirty patients with Stage III limited small cell lung cancer were initially received more than one cycle of cisplatin/etoposide (PE) or PE/CAV (cyclophosphamide, adriamicin and vincristine) followed by thoracic irradiation (total radiation dose ranged 40 Gy to 60 Gy (mean 54 Gy) with conventional fractionation). Sixteen patients received thoracic radiation concurrently with from one to three cycles of systemic chemotherapy (PE) or bronchial arterial infusin of cisplatin. The median survival time (MST) of overall cases was 17 months and 3-year survival rate was 17%, whereas MST and 3-year survival rate for patients received thoracic irradiation concurrently with chemotherapy were 19 months and 28% (n.s). Although patients recived thoracic irradiation encompassing the post induction chemotherapy volumes, five patients (17%) had WHO Grade 3 lung toxicities and two patients (7%) died from radiation pneumonitis. From these results thoracic radiation after induction chemotherapy is quite promising in the treatment of bulky small cell lung cancer with acceptable toxicity. Further studies were necessary to optimize the treatment results.

on the process M. Sumi, H. Ikeda, T. Uno, R. Hare, T. Teshima, K. Tanisada, T. Inoue.

Japanese PCS Working Subgroupof Lung Cancer, Japan Background: A Patterns of Care Study (PCS) was conducted in 19951997 to determine the national average in treating patients with lung cancer. Methods: A national survey of 70 institutions (academic 35 and nonacademic 35) using 4-stage cluster sampling was conducted and specific information was selected on 982 lung cancer patients who received thoracic radiation therapy (RT) as part of definitive or adjuvant management. Results: As for external beam equipment, linear accelerators with 6 MV or more were used for 91% of the patients in academic institutions. However, in nonacademic institutions, 39% were treated with lower energy. Eight hundred and twenty patients (83.6%) were diagnosed as non-small cell lung cancer (NSCLC) and 162 (16.4%) were small cell lung cancer (SCLC). Twelve percent were Stage I, 12% stage II, and 76% stage II1. In NSCLC, treatments which excluded surgery (nonsurgery group) was 76% and those including surgery (surgery group) was 24%. In NSCLC non-surgery group, stage I and II were more frequently treated at nonacademic than academic institutions (18% vs. 27%, respectively). Primary tumor dose more than 60 Gy was delivered in 68% at academic and 61% at nonacademic institutions. Spinal cord dose of >50 Gy was delivered evenly at both institutions (11% vs. 10%, respectively). Chemoradiotherapy was performed significantly more frequently at academic than nonacademic institutions (58% vs. 45%, respectively). Conclusions: Some differences in the equipment and treatment methods, such as frequency of use of chemoradiotherapy for lung cancer were noted between academic and nonacademic institutions in Japan. This survey justified that the institutional stratification significantly affected the patterns of care for lung cancer. ~-~

Thoracic irradiation combined with chemotherapy in bulky small cell lung cancer

T. Kaizu, K. Karasawa, H. Ishikawa, R. leki, ¥. Tanaka 1. Dept. of

Radiology and Internal Medicine, Tokyo Metropolitan Komagome Hospital; 1Dept. of Radiology, Nihon Univercity, Tokyo, Japan For limited small cell lung cancer, thoracic radiation and chemotherapy improves survival, a meta-analysis of trials suggested that beginning thoracic irradiation concurrently with cisplatin and etoposide has potentially advantages over sequential treatment. But in bulky limited small cell lung cancer, early beginning of thoracic irradiation

[ - 5 - ~ The effects of radiotherapy in the treatment of patients with vena cava superior (SyVCS) M Antoni6 ~, M. Gavrilovi~2, N. Se(~en. 1Institute for Lung Diseases,

Sremska Kamenica; 2Institute of Oncology, Department of Radiotherapy, Sremska Kamenica, Yugoslavia The authors present the analyses of 338 patients with SyVCS treated in ten years period, 284 males and 54 females, average ages 56.7. The examined group included 219 patients with a histologically confirmed lung cancer, (108 with small cell lung carcinoma - SCLC, 81 patients with squamous lung cancer, 50 patients with adenocarcinoma) unlike 119 patients who lacked a histologic diagnosis. All patients were with clinical signs of SyVCS and they underwent chest-Xray irradiation, from vital indications. Split course regimen hyperfractionation and individual doses of fractionation were administrated. The effects of different radiotherapy types were compared due to histological type of luod cancer. SyVCS was decreased (complete remission and partial remission) in 203 patients (89.6%). No change were in 21 patients (6.3%) and progression was found in 14 patients (13.86%). The median survival was 4.7 months. Overall survival was presented by Kaplan-Meier curve. The survival was in positive correlation of histological type of lung cancer as well as the radiotherapy form.

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IrradiaUon myelopathy in NSCLC patients following adjuvant postoperative irradiation

J. Stanic, M Kakas, C. Nadj, Z. Eri, G. Kozlovacki. Institute for Lung

Diseases, Sremska Kamenica, Yugoslavia The spinal cord lesions induced by accidental irradiation in the course of radio therapy were for the first time registered in 1948 (N Boden, A. Stark, J. Grennfield). The term includes three clinical presentations: transitory subacute myelopathy, selective motor disorders bellow the irradiation area and delayed progressive irradiation myelopathy (DPM). DPM, the most severe form, is registered in 1-12% of accidental irradiations. The symptoms develop after a latent period of 12-14 months. Neurologic disorders correlate with the level of the affected spine segment and are presented by paresthesia, motor defects of paraparesis and paraplegia, with or without sphincter control loss. Eight patients with neurologic symptoms, developing in single patients over the post-irradiation period of 8-16 months, have been observed since 1996. The symptoms were initially progressive, taking then the form of fixed neurologic defects. By additional examinations the presence of the tumor relapse or distant metastases were eliminated. The spine MRI revealed no myelon metastases in any of the patients but