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or endobronchial irradiation as pretreatment in external radiation therapy for patients with inoperable non-small cell lung cancer: an interim analysis
139 533
534
RE-IRRADIATION OF NON-SMALL CELL LUNG CANCER. J.F. Littles,
Photodynnmic therapy and/or endobronchisl irradiation as pretreatment in external radiation therapy for patients with inoperable non-small cell lung cancer: an interim analysis. N. van Zandwijk, P., G. Baris, H. Bartelink for the BRAPHO Study Group. The Netherlands Cancer Institute. Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
A.T. Turrisi, M.B. Hazuka, V. Massey, M. Martel, University of Michigan Hospital, Ann Arbor, Michigan, USA. Patients previously irradiated for non-small cell lung cancer at times develop recurrent local symptoms. These local symptoms include hernoptysis, post destructive pneumonia, and localized pain secondary to involvement of adjacent organs. Chemotherapy has not been shown to be effectiue in these patients. Laser or brachytberapy may not be technically feasible. Therefore, w-irradiation appears to be a reasonable option for these patients. This report presents our experience with w-irradiation in non-small cell lung cancer. From March of 1990 until October of 1992, eight patients have been seen in our department who subsequently required definitive radiation treatment to a previously irradiated area. All patients were treated using our three dimensional treatment planning system. The second course of radiation was done entirely off cord. The total accumulative dose range from 91 Gy to 133.6 Gy, with the mean dose of 97.36 Gy. Follow-up range from two months to forty-three months, with a mean of eighteen months. Four patients are alive with disease. only one patient developed a grade II pneumonitis. There were no other complications reported. This paper shows that re-irradiation of non-small lung cancer can be done in a safe and effective manner. The techniques of w-irradiation will be discussed. This provides an alternate therapy for patients with symptomatic disease outside a bronchus. More patients will be required to define safety and efficacy.
Photodynamic therapy (PDT) and endobroncbial high dose irradiation (HDR) have shown to be effective in the treatment of central intraluminal non-small
cell lung cancer (NSCLC). However, the proper place and indication for both modalities is not yet established in relation to external radiation therapy (ERT). Therefore we have initiated a prospective randomized multicenter study to evaluate the additional effect of PDT or HDR preceding ERT. Patients with histologically proven inoperable locoregional NSCLC, without loss of weight
< 10% and a PS of > 70% are eligible in this three arms study comparing ERT alone with PDT or HDR preceding ERT. PDT, using Photofrin (2 mg/kg, cylindrical diffuser, 200 J/cm, 630 nm) or HDR (15 Gy at 1 cm distance along the tumor site with a margin of 1 cm) is given 2 weeks before ERT. The ERT schedule consists of 14 x 2.5 + surdosage of 8 x 2.5 Gy to the tumor area in 4 weeks. So far we have included 55 patients of which 12 patients were too early to be included in the analysis. Of the 43 patients analyzed (9:6 = 5:38) 6 presented with stage I and II and 37 presented with stage III. Four patients were ineligible as a consequence of distant metastaw in three and SCLC at review in one. Of the 39 remaining patients, 12 patients received ERT alone, 12 HDR-ERT and 15 PDT-ERT. The combined treatments were well tolerated when compared to ERT alone. Side effects observed were: moderate radiation fibrosis in 4 patients, minor hemoptysis in 2 patients of the PDT-ERT group.
Eight patients suffered from grade 2 and 2 grade 3 esophagitis after ERT. Skin photosensitivity was acceptable in the patients treated with PDT. Fatal hemoptysis occurred in one patient 14 months after protocol treatment. Since the majority of the patients presented with stage III disease, a median survival of 16 months was considered as encouraging. Updated results will be presented.
536 EARLY THREE
EFFECTS OF FRACTIONATED IRRADIATION DIFFERENT VOLUMES OF CANINE LUNG.
OF
J.M. Paulson, S.M. Gillette, P.F. Steyn, C.A. Dawson’, D.A. Rickaby’, E.L. Chancy’, E.L. Gillette, Department of Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523, ‘V.A. Medical Center, Milwaukee, WI 53295, ‘University of North Carolina, Chapel Hill, NC 27599-7512. Volume and tolerance-dose relationships for normal lung are being studied in young adult beagle dogs. A three-dimensional treatment planning system was used to determine total lung volume irradiated for each dog. Mediastinal fields of increasing width were designed to irradiate 33%, 66% or 100% of the lung volume to a range of doses between 31.5 and 67.5 Gy delivered in 1.5 Gy fractions over 6 weeks using x rays from a 6 MV clinical linear accelerator. To date fifty dogs have been treated and studied for at least three months following irradiation. Ten of these dogs developed respiratory distress as a complication of radiation pneumonitis and were euthanatized. Of the dogs which developed pneumonitis, six had 100% of their lung volume irradiated and four had 66% irradiated. No dogs irradiated to 33% of their lung volume developed pneumonitis suggesting a volume effect for the development of pneumonitis. Ventilation studies using aerosolized 99”Tc DTPA were done prior to and at three months after treatment. The rate of clearance from the lungs is considered a function of capillary perfusion. Serotonin uptake, a measure of endothelial cell function, was assessed prior to and at three months after treatment. Results presented are preliminary data from a study that is ongoing. Funded by NIH Grant CA 13899-20
EVALUATION OF THE RESPONSE TO ENDOGENOUS PORPHYRIN PHOTODYNAMIC THERAPY OF SMALL CELL LUNG CANCER CELL LINES. D.L. Campbell, M.E. Fisher, R.H. Pottier, B.G. Campling, J.C. Kennedy. Queen’s University, Kingston, Ontario, Canada, K7L 3N6. Endogenous protoporphyrin IX (PpIX), induced by administration of the heme precursor 5-aminolevulinic acid (ALA), is a clinically useful photosensitizer for photodynamic therapy (PDT) (J. Photochem. Photobiol. B: Biol., 14:275 (1992)). The purpose of this study was to evaluate the accumulation of PplX and to correlate it with the phototoxic response to light in a series of SCLC cell lines. Five patientderived SCLC lines were chosen based on their extremes of resistance to various chemotherapeutic agents. Following incubation with ALA, a Coulter Elite Flow Cytometer was utilized to measure the accumulation of the ALA-induced PplX fluorescence. A modified fluorescein diacetate flow cytometric technique was used to measure the survival of the treated cells (5 mM ALA, light 600-700 nm, - 120 mwlcm’). All of the SCLC cell lines studied to date accumulated PplX and exhibit a cytotoxic response to PDT. A good correlation was observed between the ALA-induced PplX accumulation and response to light treatment, as seen by differences in the photoradiation survival curves. Ongoing studies will determine the response to PDT of drug resistant SCLC cell lines which have been selected in vim and demonstrate a known mechanism of drug resistance.
534
RE-IRRADIATION OF NON-SMALL CELL LUNG CANCER. J.F. Littles,
Photodynnmic therapy and/or endobronchisl irradiation as pretreatment in external radiation therapy for patients with inoperable non-small cell lung cancer: an interim analysis. N. van Zandwijk, P., G. Baris, H. Bartelink for the BRAPHO Study Group. The Netherlands Cancer Institute. Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
A.T. Turrisi, M.B. Hazuka, V. Massey, M. Martel, University of Michigan Hospital, Ann Arbor, Michigan, USA. Patients previously irradiated for non-small cell lung cancer at times develop recurrent local symptoms. These local symptoms include hernoptysis, post destructive pneumonia, and localized pain secondary to involvement of adjacent organs. Chemotherapy has not been shown to be effectiue in these patients. Laser or brachytberapy may not be technically feasible. Therefore, w-irradiation appears to be a reasonable option for these patients. This report presents our experience with w-irradiation in non-small cell lung cancer. From March of 1990 until October of 1992, eight patients have been seen in our department who subsequently required definitive radiation treatment to a previously irradiated area. All patients were treated using our three dimensional treatment planning system. The second course of radiation was done entirely off cord. The total accumulative dose range from 91 Gy to 133.6 Gy, with the mean dose of 97.36 Gy. Follow-up range from two months to forty-three months, with a mean of eighteen months. Four patients are alive with disease. only one patient developed a grade II pneumonitis. There were no other complications reported. This paper shows that re-irradiation of non-small lung cancer can be done in a safe and effective manner. The techniques of w-irradiation will be discussed. This provides an alternate therapy for patients with symptomatic disease outside a bronchus. More patients will be required to define safety and efficacy.
Photodynamic therapy (PDT) and endobroncbial high dose irradiation (HDR) have shown to be effective in the treatment of central intraluminal non-small
cell lung cancer (NSCLC). However, the proper place and indication for both modalities is not yet established in relation to external radiation therapy (ERT). Therefore we have initiated a prospective randomized multicenter study to evaluate the additional effect of PDT or HDR preceding ERT. Patients with histologically proven inoperable locoregional NSCLC, without loss of weight
< 10% and a PS of > 70% are eligible in this three arms study comparing ERT alone with PDT or HDR preceding ERT. PDT, using Photofrin (2 mg/kg, cylindrical diffuser, 200 J/cm, 630 nm) or HDR (15 Gy at 1 cm distance along the tumor site with a margin of 1 cm) is given 2 weeks before ERT. The ERT schedule consists of 14 x 2.5 + surdosage of 8 x 2.5 Gy to the tumor area in 4 weeks. So far we have included 55 patients of which 12 patients were too early to be included in the analysis. Of the 43 patients analyzed (9:6 = 5:38) 6 presented with stage I and II and 37 presented with stage III. Four patients were ineligible as a consequence of distant metastaw in three and SCLC at review in one. Of the 39 remaining patients, 12 patients received ERT alone, 12 HDR-ERT and 15 PDT-ERT. The combined treatments were well tolerated when compared to ERT alone. Side effects observed were: moderate radiation fibrosis in 4 patients, minor hemoptysis in 2 patients of the PDT-ERT group.
Eight patients suffered from grade 2 and 2 grade 3 esophagitis after ERT. Skin photosensitivity was acceptable in the patients treated with PDT. Fatal hemoptysis occurred in one patient 14 months after protocol treatment. Since the majority of the patients presented with stage III disease, a median survival of 16 months was considered as encouraging. Updated results will be presented.
536 EARLY THREE
EFFECTS OF FRACTIONATED IRRADIATION DIFFERENT VOLUMES OF CANINE LUNG.
OF
J.M. Paulson, S.M. Gillette, P.F. Steyn, C.A. Dawson’, D.A. Rickaby’, E.L. Chancy’, E.L. Gillette, Department of Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523, ‘V.A. Medical Center, Milwaukee, WI 53295, ‘University of North Carolina, Chapel Hill, NC 27599-7512. Volume and tolerance-dose relationships for normal lung are being studied in young adult beagle dogs. A three-dimensional treatment planning system was used to determine total lung volume irradiated for each dog. Mediastinal fields of increasing width were designed to irradiate 33%, 66% or 100% of the lung volume to a range of doses between 31.5 and 67.5 Gy delivered in 1.5 Gy fractions over 6 weeks using x rays from a 6 MV clinical linear accelerator. To date fifty dogs have been treated and studied for at least three months following irradiation. Ten of these dogs developed respiratory distress as a complication of radiation pneumonitis and were euthanatized. Of the dogs which developed pneumonitis, six had 100% of their lung volume irradiated and four had 66% irradiated. No dogs irradiated to 33% of their lung volume developed pneumonitis suggesting a volume effect for the development of pneumonitis. Ventilation studies using aerosolized 99”Tc DTPA were done prior to and at three months after treatment. The rate of clearance from the lungs is considered a function of capillary perfusion. Serotonin uptake, a measure of endothelial cell function, was assessed prior to and at three months after treatment. Results presented are preliminary data from a study that is ongoing. Funded by NIH Grant CA 13899-20
EVALUATION OF THE RESPONSE TO ENDOGENOUS PORPHYRIN PHOTODYNAMIC THERAPY OF SMALL CELL LUNG CANCER CELL LINES. D.L. Campbell, M.E. Fisher, R.H. Pottier, B.G. Campling, J.C. Kennedy. Queen’s University, Kingston, Ontario, Canada, K7L 3N6. Endogenous protoporphyrin IX (PpIX), induced by administration of the heme precursor 5-aminolevulinic acid (ALA), is a clinically useful photosensitizer for photodynamic therapy (PDT) (J. Photochem. Photobiol. B: Biol., 14:275 (1992)). The purpose of this study was to evaluate the accumulation of PplX and to correlate it with the phototoxic response to light in a series of SCLC cell lines. Five patientderived SCLC lines were chosen based on their extremes of resistance to various chemotherapeutic agents. Following incubation with ALA, a Coulter Elite Flow Cytometer was utilized to measure the accumulation of the ALA-induced PplX fluorescence. A modified fluorescein diacetate flow cytometric technique was used to measure the survival of the treated cells (5 mM ALA, light 600-700 nm, - 120 mwlcm’). All of the SCLC cell lines studied to date accumulated PplX and exhibit a cytotoxic response to PDT. A good correlation was observed between the ALA-induced PplX accumulation and response to light treatment, as seen by differences in the photoradiation survival curves. Ongoing studies will determine the response to PDT of drug resistant SCLC cell lines which have been selected in vim and demonstrate a known mechanism of drug resistance.