Patterns of disease failure after trimodality therapy of nonsmall cell lung carcinoma pathologic...

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Ahstrac,ts 111 Lung Ccrncrr 16 (1996) 105- 127 125 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 irradia- tion. 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. Can- cer 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. Pa- tients 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. Pa- tients 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 deter- mined by clinical, radiographic, or histologic criteria. Pattern of dis- ease failure was identified by site of involvement at first recurrence as indicated by the CALGB Respiratory Follow-Up Form. Results: Sixty- three 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 chemo- radiation 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 pro- gressed 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 occurred in 14 of 17 patients with muese&ble disease: local only: 6; both local and distant sites: 8. Among the 52 total patients experienc- ing disease relapse, isolated or combined local failure occurred com- monly among patients during induction chemotherapy (n = 10, [28%]), in those with unreseaable disease (n = 14, (39%]), or in those with resected disease (n = 12, [33%]), (F’ = NS). However, isolated or com- bined distant failure was more likely to occur among patients with resected disease (n = 27, [69%]) than either during induction chemo- therapy (n = 4. [IO%]) or in those with umesecteddisease(n=8,[21%]). (F < 0.05). Among patients who relapsed, brain metastases occurred in 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 thera- peutic 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 Bout- eva&, 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 discour- aging. Long- term disease control and cure rates with a single modality approach with surgery or radiotherapy have been poor; this is particu- laly 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 sur- gery. 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 sur- gery 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 Fac- ulty ofMedicine, Kyushu University. Fukuoka 812-82. Ann Nucl Med 1996;lO: 193-200. The clinical usefulness of FDG-PET in the prediction and assess- ment 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 classi- fiedaseitherapartialresponse(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 up- take 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-

Transcript of Patterns of disease failure after trimodality therapy of nonsmall cell lung carcinoma pathologic...

Ahstrac,ts 111 Lung Ccrncrr 16 (1996) 105- 127 125

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 irradia- tion.

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. Can- cer 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. Pa- tients 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. Pa- tients 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 deter- mined by clinical, radiographic, or histologic criteria. Pattern of dis- ease failure was identified by site of involvement at first recurrence as indicated by the CALGB Respiratory Follow-Up Form. Results: Sixty- three 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 chemo- radiation 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 pro- gressed 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 occurred in 14 of 17 patients with muese&ble disease: local only: 6; both local and distant sites: 8. Among the 52 total patients experienc- ing disease relapse, isolated or combined local failure occurred com- monly among patients during induction chemotherapy (n = 10, [28%]), in those with unreseaable disease (n = 14, (39%]), or in those with resected disease (n = 12, [33%]), (F’ = NS). However, isolated or com- bined distant failure was more likely to occur among patients with resected disease (n = 27, [69%]) than either during induction chemo- therapy (n = 4. [IO%]) or in those with umesecteddisease(n=8,[21%]). (F < 0.05). Among patients who relapsed, brain metastases occurred in

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 thera- peutic 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 Bout- eva&, 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 discour- aging. Long- term disease control and cure rates with a single modality approach with surgery or radiotherapy have been poor; this is particu- laly 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 sur- gery. 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 sur- gery 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 Fac- ulty ofMedicine, Kyushu University. Fukuoka 812-82. Ann Nucl Med 1996;lO: 193-200.

The clinical usefulness of FDG-PET in the prediction and assess- ment 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 classi- fiedaseitherapartialresponse(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 up- take 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-