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Radiotherapy as an alternative to surgery in elderly patients with resectable lung cancer
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Etoposide compared with the combination of vincriatine, doxornbitin, and cyclophosphamide in the treatment of small ceil lung cancer. MclllmurrayMB,BibbyRJ,TaylorBEetal.Royallancasferlnfirmary, Lancaster. LA1 4RR. Thorax 1989:44:215-9.
Chte hundred and three patients with small cell lung carcinoma were stratilied according to stage of disease (47 limited disease, 56 extensive disease) and then randomised to receive etoposide 300 mglm’alone for two days or a combination (VAC) of vincristine 1 mg/m’, doxorubicin (Adriamycin)50mg/m2,andcyclophosphamide 1OOOmg/m*.Thedrngs were given at three week intervals. Patients were assessed after three
cycles of treatment and continued with the same regimen if in complete remission and with the alternative regimen if in partial remission: they were withdrawn if the disease had progressed. Twenty four patients (23%) achieved complete remission and this occurred more often when patients were receiving VAC (19 of 82) than etoposide (5 of 75). There was no difference, however, in overall survival between those initially treated with etoposide and those having combination chemotherapy, whether for limited disease (both 8 months) or extensive disease (7 and 5.5 months). Toxicity was less with etoposide. Survival was disappointing, especially with limited disease, even in patients who showed a complete response to treatment.
Radiotherapy Radiotherapy as an alternative to surgery in elderly patients with resectable lung cancer.
NoordijkEM,VdPoestClementE,HermansJ,
WeverAMJ,LeerJWH.
Department of Clinical Oncology, University Hospifal, 2300 RC L&iden. Radiother Oncol 1988;13:83-9. Fmm 1978 to 1983,50 patients with a peripherally located non-small
cell tumorofthelungwereirradiatedwithcurativeintent.Thesepatienrs werenotoperateduponbccauseofpoorcardiacorpulmonarycondition, old age or refusal to operate. Mean age was 74 years, 40 patients being over 70 years of age. All patients had T,, N& tumors according to the AJC classification and received 60 Gy to the primary tumor only. The overall response rate was 90%. with 50% complete responses in tumors smaller than 4 cm. The crude overall survival rates were 56% at 2 years and 16% at 5 years, with a median survival of 27 months. Age did not influence survival. There was a strong correlation of survival to tumor size, with 5year survival rates of 38, 22, 5 and 0% in tumors with diameters of -2, 2-3, 3-4 and >4 cm respectively. Only 5 out of 20 complete responders had a local recurrence, (he 5.year survival in this group was 42%. These results compared favorably to a group of 86 patientsover70yearsofage who wereselectedforoperationinthesame hospital. The 2- and 5-year survival rates in these patients were 48 and 26% respectively, median survival being 23 months. We conclude that in patients over 70 years of age with resectable lung cancer, radiotherapy with curative intent should be offered as an alternative to operation, especially if the tumor is not larger than 4 cm. The wait-and-see policy in inoperable patients of this age group must be abandoned. Radiosensitivity related to neuroendocrine and endodermal differentiation in lung carcinoma lines. Duchesne G, Cassoni A, Pera M. Insrirufe ofCancer Research. Sutton, Surrey SM2 5fX. Radiother Oncol 1988;13:153-61.
A panel of human lung carcinoma lines was studied with respect to hormone production and intermediate filament expression to distinguish between endodermal and neuroendocrine differentiation. An Index of the degree of neuroendccrine differentiation of each line was derived from the presence or absence of hormone production, cytokeratins, neurotilaments and an embryonic endodermal cell marker, which allowedidentificationofthreegroupsshowinghigh,intermediateorlow neuroendocrine expression. This grouping correlated well with the in vitro radiosensitivity of the lines, those expressing pure neuroendocrine features being significantly more radiosensitive than those with an endcdermal phenotype, with the intermediate group having intermediate sensitivity. Use of such an index might predict those patients likely to benefit from the use of radiotherapy in their management. Radiation-induced lung damage: Dose-time-fractionation considerations. Van Dijk J, Mah K, Keane TJ. Ontario Cancer Institute/Princess Margaret Hospital. Toronto. Ont. M3X IK9. Radiother Oncol 1989;14:55-69. The comparison of different dose-time-fractionation schedules requiresthe useofan isoeffect formula. In recent years, theNSD &effect
formula has been heavily criticized. In this report, we consider an isoeffect formula which is specifically developed for radiation-induced lung damage. The formula is based on the linear-quadratic model and includes a factor for overall treatment time. The pmposed procedures allow for the simultaneous derivation of an JO ratio and a gamma8 time factor. From animal data in the literature, the derived JB and gamma/ 8 ratios for acute lung damage are 5.0 * 1.0 Gy and 2.7 * 1.4 Gy’/day respectively, while for late damage the suggested values are 2.0 Gy and 0.0 Gy?day. Data from two clinical studies, one prospective and the other retrospective, were also analysed and corresponding J8 and gammaA ratios were determined. For the prospective clinical study, with a limited range of doses per fraction, the resultant Jl3 and gamma/ 8 ratios were 0.9 * 2.6 Gy and 2.6 * 2.5 Gy*/day. The combination of the retrospective and prospective data yielded JO and gamma/l3 ratios of 3.3 1.5 Gy and 2.4 1.5 Gy2/day, respectively. One potential advantageof this isoeffect formalism is that it mightpossibly beapplied to both acute and late lung damage. The results of this formulation for acute lung damage indicate that time-dependent effects such as slow repair or proliferation might be more important in determining isoeffcct doses than previously predicted by the estimated single dose (ED) formula. Althogh we present this as an alternative approach, we would caution against its clinical use until its applicability has been confirmed by additional clinical data. ??
??
Response of human tumor cell lines in vitro to fractionated irradiation. Matthews JHL, Meeker BE, Chapman JD. Deparfment of Radiafion Oncology, Cross Cancer Instinte, Edmonton. Alta. T6G 122. Int I
Radiat Oncol Biol Phys 198916: 133-8. The surviving fraction of human tumor cell lines after 2 Gy (SF,) varies between 0.1 and 0.8. It has been postulated that differences in inherent radiosensitivity of tumor cells are a major determinant of radiation response in viva. Assays of inherent radiosensitivity based on acute survival are being developed as predictors of tumor response which often assume that the same inherent radiosensitivity persists throughout a fractionated treatment. We have investigated the response of 2 human tumor cell lines (A549 and MCF7) with different inherent radiosensitivities to in vitro fractionated irradiation. A549 cells had an SF, of 0.62 and a mean inactivation dose (D-)of 3.07 Gy whereas MCF7 cells had an SF, of 0.30 and a D- of 1.52 Gy. Split dose repair capacity (at equal survival levels) was less for A549 than for MCF7 cells and recovery kinetics for both cell lines were substantially longer than those of rodent cell lines. Survival after 5 fractions of 2 Gy given 12 hr apart at 37’C was near to that predicted from the acute survival curve, assuming complete repair and no proliferation. Acute survival of A549 cells which survived 5 fractions of 2 Gy given 12 hr apart was similar to the acute survival of unitradiated cells, When A549 cells were incubated at 22’C between 5 fractions of 2 Gy given I2 hr apart, proliferation and split dose repair were substantially inhibited. These studies support the pmposals to use in vitro inherent radiosensitivity assays for the prediction of in viva response of tumors to fractionated treatment.
Etoposide compared with the combination of vincriatine, doxornbitin, and cyclophosphamide in the treatment of small ceil lung cancer. MclllmurrayMB,BibbyRJ,TaylorBEetal.Royallancasferlnfirmary, Lancaster. LA1 4RR. Thorax 1989:44:215-9.
Chte hundred and three patients with small cell lung carcinoma were stratilied according to stage of disease (47 limited disease, 56 extensive disease) and then randomised to receive etoposide 300 mglm’alone for two days or a combination (VAC) of vincristine 1 mg/m’, doxorubicin (Adriamycin)50mg/m2,andcyclophosphamide 1OOOmg/m*.Thedrngs were given at three week intervals. Patients were assessed after three
cycles of treatment and continued with the same regimen if in complete remission and with the alternative regimen if in partial remission: they were withdrawn if the disease had progressed. Twenty four patients (23%) achieved complete remission and this occurred more often when patients were receiving VAC (19 of 82) than etoposide (5 of 75). There was no difference, however, in overall survival between those initially treated with etoposide and those having combination chemotherapy, whether for limited disease (both 8 months) or extensive disease (7 and 5.5 months). Toxicity was less with etoposide. Survival was disappointing, especially with limited disease, even in patients who showed a complete response to treatment.
Radiotherapy Radiotherapy as an alternative to surgery in elderly patients with resectable lung cancer.
NoordijkEM,VdPoestClementE,HermansJ,
WeverAMJ,LeerJWH.
Department of Clinical Oncology, University Hospifal, 2300 RC L&iden. Radiother Oncol 1988;13:83-9. Fmm 1978 to 1983,50 patients with a peripherally located non-small
cell tumorofthelungwereirradiatedwithcurativeintent.Thesepatienrs werenotoperateduponbccauseofpoorcardiacorpulmonarycondition, old age or refusal to operate. Mean age was 74 years, 40 patients being over 70 years of age. All patients had T,, N& tumors according to the AJC classification and received 60 Gy to the primary tumor only. The overall response rate was 90%. with 50% complete responses in tumors smaller than 4 cm. The crude overall survival rates were 56% at 2 years and 16% at 5 years, with a median survival of 27 months. Age did not influence survival. There was a strong correlation of survival to tumor size, with 5year survival rates of 38, 22, 5 and 0% in tumors with diameters of -2, 2-3, 3-4 and >4 cm respectively. Only 5 out of 20 complete responders had a local recurrence, (he 5.year survival in this group was 42%. These results compared favorably to a group of 86 patientsover70yearsofage who wereselectedforoperationinthesame hospital. The 2- and 5-year survival rates in these patients were 48 and 26% respectively, median survival being 23 months. We conclude that in patients over 70 years of age with resectable lung cancer, radiotherapy with curative intent should be offered as an alternative to operation, especially if the tumor is not larger than 4 cm. The wait-and-see policy in inoperable patients of this age group must be abandoned. Radiosensitivity related to neuroendocrine and endodermal differentiation in lung carcinoma lines. Duchesne G, Cassoni A, Pera M. Insrirufe ofCancer Research. Sutton, Surrey SM2 5fX. Radiother Oncol 1988;13:153-61.
A panel of human lung carcinoma lines was studied with respect to hormone production and intermediate filament expression to distinguish between endodermal and neuroendocrine differentiation. An Index of the degree of neuroendccrine differentiation of each line was derived from the presence or absence of hormone production, cytokeratins, neurotilaments and an embryonic endodermal cell marker, which allowedidentificationofthreegroupsshowinghigh,intermediateorlow neuroendocrine expression. This grouping correlated well with the in vitro radiosensitivity of the lines, those expressing pure neuroendocrine features being significantly more radiosensitive than those with an endcdermal phenotype, with the intermediate group having intermediate sensitivity. Use of such an index might predict those patients likely to benefit from the use of radiotherapy in their management. Radiation-induced lung damage: Dose-time-fractionation considerations. Van Dijk J, Mah K, Keane TJ. Ontario Cancer Institute/Princess Margaret Hospital. Toronto. Ont. M3X IK9. Radiother Oncol 1989;14:55-69. The comparison of different dose-time-fractionation schedules requiresthe useofan isoeffect formula. In recent years, theNSD &effect
formula has been heavily criticized. In this report, we consider an isoeffect formula which is specifically developed for radiation-induced lung damage. The formula is based on the linear-quadratic model and includes a factor for overall treatment time. The pmposed procedures allow for the simultaneous derivation of an JO ratio and a gamma8 time factor. From animal data in the literature, the derived JB and gamma/ 8 ratios for acute lung damage are 5.0 * 1.0 Gy and 2.7 * 1.4 Gy’/day respectively, while for late damage the suggested values are 2.0 Gy and 0.0 Gy?day. Data from two clinical studies, one prospective and the other retrospective, were also analysed and corresponding J8 and gammaA ratios were determined. For the prospective clinical study, with a limited range of doses per fraction, the resultant Jl3 and gamma/ 8 ratios were 0.9 * 2.6 Gy and 2.6 * 2.5 Gy*/day. The combination of the retrospective and prospective data yielded JO and gamma/l3 ratios of 3.3 1.5 Gy and 2.4 1.5 Gy2/day, respectively. One potential advantageof this isoeffect formalism is that it mightpossibly beapplied to both acute and late lung damage. The results of this formulation for acute lung damage indicate that time-dependent effects such as slow repair or proliferation might be more important in determining isoeffcct doses than previously predicted by the estimated single dose (ED) formula. Althogh we present this as an alternative approach, we would caution against its clinical use until its applicability has been confirmed by additional clinical data. ??
??
Response of human tumor cell lines in vitro to fractionated irradiation. Matthews JHL, Meeker BE, Chapman JD. Deparfment of Radiafion Oncology, Cross Cancer Instinte, Edmonton. Alta. T6G 122. Int I
Radiat Oncol Biol Phys 198916: 133-8. The surviving fraction of human tumor cell lines after 2 Gy (SF,) varies between 0.1 and 0.8. It has been postulated that differences in inherent radiosensitivity of tumor cells are a major determinant of radiation response in viva. Assays of inherent radiosensitivity based on acute survival are being developed as predictors of tumor response which often assume that the same inherent radiosensitivity persists throughout a fractionated treatment. We have investigated the response of 2 human tumor cell lines (A549 and MCF7) with different inherent radiosensitivities to in vitro fractionated irradiation. A549 cells had an SF, of 0.62 and a mean inactivation dose (D-)of 3.07 Gy whereas MCF7 cells had an SF, of 0.30 and a D- of 1.52 Gy. Split dose repair capacity (at equal survival levels) was less for A549 than for MCF7 cells and recovery kinetics for both cell lines were substantially longer than those of rodent cell lines. Survival after 5 fractions of 2 Gy given 12 hr apart at 37’C was near to that predicted from the acute survival curve, assuming complete repair and no proliferation. Acute survival of A549 cells which survived 5 fractions of 2 Gy given 12 hr apart was similar to the acute survival of unitradiated cells, When A549 cells were incubated at 22’C between 5 fractions of 2 Gy given I2 hr apart, proliferation and split dose repair were substantially inhibited. These studies support the pmposals to use in vitro inherent radiosensitivity assays for the prediction of in viva response of tumors to fractionated treatment.