High dose rate brachytherapy for the local control of endobronchial carcinoma following external irradiation

(19%) topenia patients similar vanced

and four (9%) patients respectively, but only grade 2 thrombocywas observed. Phlebitis at the infusion sire was observed in 24 (53%). This treatment programme achieved a response rate to other active combination regimens for the treatment of adNSCLC, and was less toxic.

A phase II study of mitomycin C, vindesine and cisplatin combined with alpha interferon in advanced non-small cell lung cancer Silva RR, Bascioni R, Rossini S. Servizio di Oncologia Medica, Ospedale ‘Profili’, 60044 Fabriano. Tumori 1996;82:68-71. Aims and background MVP chemotherapy (mitomycin C, vi&sine or vinblastine, cisplatin) is one of the most commonly used regimens for advanced non-small cell lung cancer (NSCLC). Experimental data suggest a synergistic cytotoxic activity of alpha-interferon (a-IFN) when combined with cisplatin, mitomycin C, and vinca alkaloids. In an effort to improve MVP chemotherapy activity, we have combined this regimen with a-IFN. Patients and methods: Thirty-five patients with advanced NSCLC (19 stage IV) were treated with the MVP regimen (mitomycin C, 8 mg/m*; vindesine, 3 mg/m*; cisplatin, 75 mg/m*, all on day 1) plus a-Za-IFN, 3 x lo6 U im from day 1 to 7. The cycles were repeated every 28 days, Results. There were no complete responses and 18 partial responses, for an overall response rate of 51%. Median time to treatment failure was 6 months (range, l-18). and median survival was 9.5 months (range, l-32). WHO grade 3 toxicity was recorded in up to 8% of patients, flu-like syndrome was a common complaint; one toxic death occurred. Conclusions: The combination yielded a level of response comparable to that of other cisplatin-based regimens. Larger randomized trials are needed to assess the role of a-JFN combined with chemotherapy in advanced NSCLC.

Cisplatin-vinorelbine combination chemotherapy in locally advanced non-smaIl cell lung cancer Frontitti L, Candid0 P, Cattaneo M et al. Ospedale Luigi Sacco. I/fa G.B. Grassi 74, 0157Milan. Tumori 1996;82:57-60. Aim: The North Milan Group presents the results of a phase11 study on a cisplatin-vinorelbine combination schedule inthe treatment of locally advanced non-small cell lung concerto evaluate its activity and tolerability, MethodsSeventy-six consecutive patients entered the study, Patients’ characteristics were the following: males/females 69/7; median age, 61.4 years (range, 40-73); ECOG performance status, O-l; 17 stage IIIa and 59 stage IIIb.There were 49 sqtamous cell carcinomas, 20 adenocarcinomas,and 7 large cell carcinomas. All patients had not beenpreviously treated and showed measurable disease. Treatment consisted of vinorelbine, 25 mg/m’ on days 1 and 8, phrscisplatin, 80 mg/ m’ on day 1, administered intravenously every 2 1 days for three standard courses. Results: Seventy-four patients were evaluable for response. Objective responses were documented in 42/74 patients with an overall response rate (CP + PR) of 56.7%;18/74 patients (24.3%) showed stable disease and the remaining 14/74 (18.9%) went into progression. Twelve patients (16.2%) were suitable for a subsequent surgery. The median duration of response was 13.3 months. Survival time ranged from 4 to 36 months: it was 14.6 months for PR patients, 8.6 months for NC and 5 months for PD. Mean survival time is presently 12.85 months (SE, 1.2 months). Toxicity evahrated on 222 cycles administered was acceptable, and it was necessary to use G-CSF or delay the treatment because of severe leukopenia in only a few cases. Conclusions: The regimen is active and safe: the slight survival increase is likely due to the small amenability to surgery achieved (16.2%). However, our results am fully comparable to others c&ained with vlnorelbine in two/three drug combination chemotherapy regimens.

Radiation treatment of superior sulcus lung carcinoma MlRar J, Ball D, Worotniuk V, Smith J, Crennan E, Bishop M. Wfiam Buckland Radiotherapy Centre. A&d Hospital. Commercial Road. Prahran. l&.3181. Australas Radio1 1996;40:55-60. The survival of patients with superior sulcus lung carcinoma and the effect; of treatment were reviewed. From a prospective database of 4123 consecutive new patients with lung carcinoma, 131 (3.2%) cases of superior sulcus lung carcinoma were identified. Seventy-four patients were planned to receive radiation with paltiative intent, 53 radical radiotherapy and one was observed only. The remaining three patients, with small-cell carcinoma, were treated with chemotherapy with or without radiotherapy. Of the 53 radically treated patients, nine were treated with pm-operative radiation prior to intended radical resection, Analysis was carried out on the effect on survival of performance status, nodal involvement, weight loss, vertebral body or rib involvement, treatment intent and radical combined modality treatment compared with radical radiation alone. The estimated median survival for the whole group was 7.6 months; for those treated radically it was 18.3 months, while for the palliatively treated patients it was 3.7 months. Radically treated patients with no initial nodal involvement had an estimated median survival of 22 months, while radically treated patients with nodal involvement had an estimated median survival of 8.4 months (P = 0.003). There were no statistically significant differences in survival between radically treated patients grouped according to initial weight loss, performance status, or vertebral body and rib involvement. Patients treated with pre-operative radiation did not survive significantly longer than patients treated with radiation alone, although the numbers are small.

High dose rate brachytherapy for the local control of endobronchial cnrcinomo following external irradiation Hernandez P, Gursahaney A, Roman T et al. Division o/Respiratory Medicine, Royal Mctoria Hospital, McGill University. Montreal, Que. H3A IAI. Thorax 19%;51:354-8. Background -External irradiation is an established palliative treatment for patients with inoperable lung cancer. However, persistent or recurrent symptoms due to local disease are common following external irradiation. The impact of high dose rare (HDR) brachytlterapy in the palliative management of patients with local sequelae of residual or recurrent endobronchial lung carcinoma following external irradiation was investigated. Methods - A prospective cohort of 29 patients (19 men, mean age 65 years) underwent HDR brachytherapy for inoperable lung cancer. All patients had completed external irradiation at least one month before entry into the study (mean (SD) dose 4400 (1481) cGy, completed 12.9 (21.3) months previously). Patients underwent outpatient bronchoscopic placement of l-3 HDR brachytherapy catheters for delivery of 750-1000 cGy of intraluminal irradiation every two weeks on 1-3 occasions. Prospective evaluation before and four weeks after completion of HDR brachytherapy included assessment of indices of level of function, symptoms, extent of atelectasis (chest radiogra,phy), and bronchoscopic determination of degree of endobronchial obstruction. Results - One hundred and eighteen catheters were placed in 8 1 treatments. Eleven of the 26 patients who underwent repeat bronchoscopy showed a reduction in the degree of endobronchial obstruction; five of 18 patients bad radiographic improvement in the extent of atelectasis. Positive reqxmse rates tanged from 25% for signs and symptoms related to pneumonitis to 69% for haemoptysis. Performance status improved in 24% of patients. ‘Bvo patients died before completion of the study pmtocol. Short term complications included one episode of non-fatal, massive baemoptysis, five of minor haemoptysis. and one pneumothorax. Conclusions - HDR brachytherapy may improve the

Ahstrac,ts

111 Lung

Ccrncrr

degree of endobronchial obstruction, atelectasis, symptoms, and level of function with minimal short term complications in patients with recurrent or residual symptomatic disease following external irradiation.

Combined treatment modalities Patterns of disease failure after trimodality therapy of nonsmall cell lung carcinoma pathologic Stage IlIA (N2): Analysis of Cancer and Leukemia Group B Protocol 8935 Kumar P, Hemdon 11 J, Langer M et al. Radiation Oncology Service, VA Medical Cente,: 1030 Jefferson Avenue, Memphis, TN 38104. Cancer 1996;11:2393-9. Background. The impact of sequential trimodality therapy on the pattern of first site disease failure in pathologic Stage IIIA (NZ) nonsmall cell lung carcinoma (NSCLC) was analyzed. METHODS. Seventy-four eligible patients with histologically documented Stage IIIA (N2) NSCLC underwent sequential trimodality therapy on Cancer and Leukemia Group B (CALGB) Protocol 8935. Treatment consisted of 2 cycles of induction cisplatin at 100 mg/m’ intravenously (i.v.) (Days 1 and 29) and vinblastine at 5 mg/m’ iv. weekly for 5 weeks followed by surgery. Surgery included a thoracotomy with resection of the primary tumor and hilar lymph nodes and a mediastinal lymph node dissection. Patients with resected disease then received an additional 2 cycles of cisplatin at 100 mg/m’ i.v. and vinblastine at 5 mg/m’ i.v. biweekly for a total of 4 doses followed by consolidative thoracic irradiation. Patients with completely resected disease received 54 Gray (Gy) whereas those with incompletely resected disease received 59.4 Gy at 1.8 Gy/ fraction (fx) once a day. Patients with unresectable disease underwent thoracic radiation therapy (TRT) treatments only to 59.4 Gy at 1.8 Gy/ fi without any additional chemotherapy. Disease recurrence was determined by clinical, radiographic, or histologic criteria. Pattern of disease failure was identified by site of involvement at first recurrence as indicated by the CALGB Respiratory Follow-Up Form. Results: Sixtythree of the 74 patients completed the induction chemotherapy as planned. Forty-six of the 63 patients underwent resection of disease whereas the remaining 17 were tmresectable. Thirty-three of the 46 resected patients completed the entire adjuvant postoperative chemoradiation treatment as planned. Ten of 17 patients with unresectable disease completed postsurglcal TRT, At a median follow-up interval of 27 months (range, 443). the 3-year overall survival and failure-free survival were 23% and 18%, respectively, for all 74 eligible patients. Overall, disease failure has occur& in 52 (70%) of the 74 eligible

patients: local only: 13 (25%); distant only: 16 (31%); and both local and distant: 23 (44%). (P = not significant FSI]. Ten patients progressed during induction chemotherapy: local only: six patients; and both local and distant failure: four patients. TWenty-eight of 46 resected patients recurred: local only: 1 (4%); both local and distant failure: 11 (39%); and distant only: 16 (57%); (P < 0.001). Disease progression disease: local only: 6; occurred in 14 of 17 patients with muese&ble both local and distant sites: 8. Among the 52 total patients experiencing disease relapse, isolated or combined local failure occurred commonly among patients during induction chemotherapy (n = 10, [28%]), disease (n = 14, (39%]), or in those with in those with unreseaable resected disease (n = 12, [33%]), (F’ = NS). However, isolated or combined distant failure was more likely to occur among patients with resected disease (n = 27, [69%]) than either during induction chemotherapy (n = 4. [IO%]) or in those with umesecteddisease(n=8,[21%]). (F < 0.05). Among patients who relapsed, brain metastases occurred in

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13 of 52 (25%) patients overall and in 12 of 28 (43%) patients with resected disease. CONCLUSIONS. Overall, disease failure was just as likely to occur in local, distant, or combined sites on CALGB Protocol 8935 using sequential trimodality therapy in the treatment of pathologic Stage IIIA (N2) NSCLC. Isolated or combined local failure occurred commonly during sequential tri- modality therapy whereas isotated or combined distant relapse was prevalent among patients with resected disease. In addition, isolated local failure was rare among patients with resected disease. The pattern of disease failure on CALGB Protocol 8935 reflects the biology of locoregional NSCLC as much as the therapeutic impact of trimodality therapy.

Preoperative

chemotherapy

for

stage IIIa non-small cell lung

cancer FossellaFV, RiveraE, Roth JA. Thoracir/HeameckMed. Oncol. Dept., Texas Univ. M.D. Anderson Can. CtE. Box 80. 1515 Holcombe Bouteva&, Houston, TX 77030. Curr Gpin Oncol 1996;8: 106-11. About 20% of patients with non-small cell lung cancer are stage IlIa at diagnosis. The treatment of stage IIIa tumors has been discouraging. Long- term disease control and cure rates with a single modality approach with surgery or radiotherapy have been poor; this is particulaly SO for N2 tumors, which account for the majority of Stage IlIa disease. In the past decade there has been interest in multimodality trcatrnent of stage IIla non-small cell lung cancer using preoperative induction chemotherapy with or without radiotherapy followed by surgery. Sewed phase II studies and two small phase III trials have shown that a strategy of induction chemotherapy with or without radiotherapy is feasible and probably does offer some survival advantage Over surgery or ra&&erapy alone. The next issue to be tackled is to determine whether the results achieved with induction chemoradiation followed by surgery are equivalent to those of chemoradiation without surgery. A phase III intergroup trial is underway to answer this question.

A clinical

evsluation of FDG-PET to assess the response in ra.. diation therapy for hronchogenic carcinoma Ichiya Y, Kuwabara Y, Sasaki M et al. Department of Radiology Faculty ofMedicine, Kyushu University. Fukuoka 812-82. Ann Nucl Med 1996;lO: 193-200. The clinical usefulness of FDG-PET in the prediction and assessment of response to radiation therapy in patients with bronchogenic carcinoma was evaluated. Thirty patients with untreated bronchogenic carcinoma were included in the study. All patients received FDGPET before the initiation Of radiation therapy, while 20 also received it after completing the therapy. The tumor to muscle ratio (JMR) was used as an index of the FDG uptake. The tumor response to therapy was classifiedaseitherapartialresponse(PR,n=2l)ornochange(NC,n=9) according to changes in the tumor size. Prognosis was made 6 months after the initiation oftherapy, and was classified as either relapse (n = 19) or non-relapse (n = 9). The FDG uptakes both before and tier therapy were compared with tumor response and prognosis. A high FDG uptake was noted in all 30 lesions before therapy. No significant difference% in the uptake before therapy was obselved according to the histological types nor T factors (UICC). The lesions with a higher uptake CruR more than 7) responded better to therapy than those with a lower uptake @ < 0.05). The decrease in the uptake after therapy tended to be more prominent in the PR group than in the NC group. The rate of relapse was higher in lesions with a higher uptake before therapy CTlMR more than 10) than in those with a lower uptake. The relapse group also showed a higher uptake after therapy than the non-relapse group. In addition, all 6 lesions showing a higher uptake (TMR more than 5) after therapy eventually relapsed (p < 0.05). ‘lb0 lesions dem-