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The clinical usefulness of post-treatment FDG-PET for prediction of prognosis in lung cancer patients treated with radiation therapy
S410
I. J. Radiation Oncology
● Biology ● Physics
Volume 57, Number 2, Supplement, 2003
respectively. Fourteen pts underwent surgical salvage immediately prior to CRT (sCRT) while 27 received CRT alone. Pts were followed until recurrence or death. sCRT pts received 5 cycles of therapy (60 Gy) and CRT pts received 7 cycles (75 Gy). The median cumulative radiation dose was 134Gy. Results: Median follow-up for surviving pts is 72.5 (53-97) months. Four year MS of 11 months and OS of 22% was observed. MS and 4 year OS in the sCRT pts was 30.2 months and 43%, and in the CRT pts it was 10.2 months and 11% (p⬍0.007). LRC at 4 years was 54% for the entire cohort, 72% for sCRT, and 54% for CRT. There was no differences in local control (p⬍0.11). Four-year PFS was 57% in the sCRT group and 27% in the CRT group (p⬍0.05). Cox regression analysis revealed that radiation dose and surgery prior to re-irradiation were significant predictors of LRC, PFS, and OS. Grade 4/5 toxicity occurred in 32% of pts. Quality of life surveys from all 6 pts alive after 4 years demonstrated satisfaction with outcome despite the toxicities incurred. Conclusions: Concomitant chemotherapy and high-dose re-irradiation for recurrent head and neck cancer produces favorable PFS; although, acute and late treatment-related toxicity is significant. A small percentage of pts achieve long-term survival, with the more favorable group being those able to undergo at least partial surgical resection.
2113
The Potential Routes of Distant Metastasis for Nasopharyngeal Carcinoma
S.H. Cheng, K. Yen, J.J. Jian, S.Y. Tsai, A. Feng, N. Chu, Y. Lin, K. Chan, C. Lin, T. Tan, C. Hsieh, A.T. Huang Radiation Oncology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan Purpose/Objective: We hypothesize that parapharyngeal space venous plexus and marrow of skull base bone are the potential routes for distant metastasis in stage I to III nasopharyngeal carcinoma (NPC). In this report, we used two sets of data to validate our hypothesis. Materials/Methods: Five hundreds and one (501) patients with NPC were enrolled in this study. Selection criteria are stage I-IVA-B patients who had primary irradiation and MRI as head and neck tumor evaluation in our hospital between 1990 and 2001. Patients who had radiation dose less than 60 Gy, and/or pre-radiation chemotherapy in outside hospital were excluded. If our hypothesis is true for patients with stage I-III without PPSE and bone invasion (T3), the risk of distant metastasis would be very low no matter whether patients receive adjuvant chemotherapy or not. Results: Of 147 patients treated between 1990 and 1997, 47 patients were stage I-III without PPSE and T3 disease and usually were treated with CCRT followed by adjuvant chemotherapy. No distant metastasis was observed in a median follow-up interval of 74 months. Of 354 patients treated after 1998, 95 patients were stage I-III patients without PPSE and T3 disease (67% were treated without adjuvant chemotherapy). The risk of developing distant metastasis is only 3% after a median follow-up 27 months. Among three patients developing distant metastases, one had a controversial interpretation of PPSE between radiologists, and one had been given neck excision biopsy before referral to our hospital. Conclusions: Our observation suggests that the risk of distant metastasis in stage I-III NPC patients without PPSE and T3 is very low. Parapharyngeal space venous plexus and marrow of skull base bone are the potential routes for hematogenous spreading in stage I-III NPC. Hematogenous spreading through neck lymph node is uncommon until neck lymph node size is greater than 6 cm or supraclavicular lymph node has been involved (N3 disease).
2114
The Clinical Usefulness of Post-treatment FDG-PET for Prediction of Prognosis in Lung Cancer Patients Treated with Radiation Therapy
Y. Nakayama, Y. Kitamoto, H. Ishikawa, J. Saitoh, H. Sakurai, T. Akimoto, M. Hasegawa, T. Nakano Radiology & Radiation Oncology, Gunma University, Maebashi, Japan Purpose/Objective: In lung cancer patients, FDG-PET is the most reliable modality in staging diagnosis and treatment planning. But the clinical usefulness of FDG-PET is still controversial in the prediction and assessment of response of radiation therapy. The timing of FDG study is also confusing. A high FDG uptake immediately after therapy due to the effect of radiation or unknown causes has been noted. In some reports, the timing of 3 or 6 months after treatment was recommended. But it is too late to consider the adjuvant therapy and to distinguish the response of radiation therapy from local recurrence. So we set the timing of evaluation approximately 4 weeks after treatment. The purpose of this study is to clarify the role of FDG-PET
Proceedings of the 45th Annual ASTRO Meeting
in lung cancer to evaluate the therapeutic effect of radiation therapy in predicting prognosis and to investigate the timing of FDG-PET after treatment. Materials/Methods: Twenty-five lung cancer patients treated with definitive radiation therapy were included in this study. Twenty-nine sites including 25 primary tumors (one patient had double cancer) and 4 lymph nodes were estimated. By histologic type, 20 patients consisted of squamous cell carcinoma. All patients underwent FDG-PET at around 4 weeks (range from 4 weeks to 8 weeks, mean 4.7 weeks) after completion of radiation therapy. The median follow-up was 10 months (ranged from 5 to 23 months). Standard uptake value (SUV) was used as an index of the FDG uptake. Results: Among 29 sites, 7 sites had local relapse. On post-treatment FDG-PET, 14 out of 29 sites showed decrease in the SUVs below 2.0 and all of them are free from tumor. In contrast, 15 sites in SUVs over 2.0 on post-treatment FGD-PET showed local relapse in 7 sites. The progression-free survival of 15 sites in SUVs over 2.0 was 67% at 6 months and 47% at 12 months. Three patients had mild FDG uptake at the area of radiation pneumonia. From the shape of FDG uptake at the area of radiation pneumonia, there was no confusion in assessing tumor response. Conclusions: These results indicate that recommended interval between FDG-PET and completion of radiation therapy is approximately 4 weeks, and FDG uptake after radiation therapy would have a prognostic significance in lung cancer patients.
2115
Gender, Limited Stage Small Cell Lung Cancer and the Experience of Concurrent Chemoradiation 1
G. Videtic, L. Stitt,2 F. Whiston2 1
Radiation Oncology, Cleveland Clinic Foundation, Cleveland, OH, 2Biometry, London Regional Cancer Centre, London, ON, Canada Purpose/Objective: Female sex is considered a positive prognostic factor when it comes to small cell lung cancer (SCLC) survival. To explore the basis for this finding, a retrospective review was carried out to determine whether the sex of patients (pts) receiving concurrent chemotherapy (ChT) and radiotherapy (RT) for limited stage SCLC (LSCLC) is associated with differences in treatment-related toxicity rates, failure patterns and survival. Materials/Methods: From 1989 to 1999, 215 LSCLC pts received 6 cycles of alternating cyclophosphamide/adriamycin/ vincristine and etoposide/cisplatin (EP), as per a NCI-Canada randomized trial “best arm”. Thoracic RT started with EP only (cycle 2 or 3) and was: 40 Gy/15 fractions/3 weeks or 50 Gy/25 fractions/5 weeks. RT fields encompassed gross and microscopic disease with 2-cm margins. Prophylactic cranial irradiation was administered to complete responders following re-staging at the discretion of the clinician. RT interruptions during concurrent ChT⫹RT were recorded as number of days and used as the “marker” for treatment toxicity. Smoking status at treatment start was recorded for all known smokers. Results: At the time of analysis, 23 pts (10.7%) were alive and 192 (89.3%) dead. Overall survival (OS) for all pts at 2 and 5 years was 22.7% and 7.2%, respectively, with median survival of 14.7 months. 126 LSCLC pts (58.6%) were men and 89 (48.4%) women. Smoking status at treatment start was recorded for 186 pts (86.5%): 107 (58%) not smoking [76 (71%) male; 31 (29%) female] and 79 (42%) smoking [36 (46%) male; 43 (54%) female] (male vs female, p⫽0.0005). There were otherwise no significant differences between the 2 groups over a range of patient- and treatment-related variables. 56 pts (26%) had treatment breaks for toxicity, for a median length of 5 days (range 1-18). The incidence of RT breaks was not related to gender (p⫽0.95). OS at 2- and 5-years were greater for women than men [30%;12.5% vs 18%;2.5%, respectively](p⫽0.07). Table 1 provides survival results according to sex, use of RT breaks and smoking status during treatment. Looking at sex and treatment interruptions: women without treatment breaks do the best, men with breaks the worst (p⫽0.002). A woman with a delay does as well as a man without. Looking at smoking status and sex: continued smoking decreases a woman’s survival (p⫽0.01). Overall, women survive longer than men irrespective of their smoking status. Males continuing to smoke on treatment did the poorest (p⫽0.005). Sites of first relapse were recorded in 132 cases (61%). Chest failures were greater in men (45%) than women (35%), with brain failure rates equivalent. Multivariable analysis of prognostic factors including smoking revealed positive benefit to female sex (HR⫽0.66; 95%CI (0.48,0.92), p⫽0.014). Conclusions: Female LSCLC patients treated with concurrent RT⫹ChT tolerated treatment as well as men but overall had better survival. Whether or not a woman smoked or experienced treatment interruptions, she survived longer than her male counterpart. Failure patterns suggested poorer control in the chest in men than women. The results suggest an intrinsic biological basis for the improved survival of women with SCLC.
S411
I. J. Radiation Oncology
● Biology ● Physics
Volume 57, Number 2, Supplement, 2003
respectively. Fourteen pts underwent surgical salvage immediately prior to CRT (sCRT) while 27 received CRT alone. Pts were followed until recurrence or death. sCRT pts received 5 cycles of therapy (60 Gy) and CRT pts received 7 cycles (75 Gy). The median cumulative radiation dose was 134Gy. Results: Median follow-up for surviving pts is 72.5 (53-97) months. Four year MS of 11 months and OS of 22% was observed. MS and 4 year OS in the sCRT pts was 30.2 months and 43%, and in the CRT pts it was 10.2 months and 11% (p⬍0.007). LRC at 4 years was 54% for the entire cohort, 72% for sCRT, and 54% for CRT. There was no differences in local control (p⬍0.11). Four-year PFS was 57% in the sCRT group and 27% in the CRT group (p⬍0.05). Cox regression analysis revealed that radiation dose and surgery prior to re-irradiation were significant predictors of LRC, PFS, and OS. Grade 4/5 toxicity occurred in 32% of pts. Quality of life surveys from all 6 pts alive after 4 years demonstrated satisfaction with outcome despite the toxicities incurred. Conclusions: Concomitant chemotherapy and high-dose re-irradiation for recurrent head and neck cancer produces favorable PFS; although, acute and late treatment-related toxicity is significant. A small percentage of pts achieve long-term survival, with the more favorable group being those able to undergo at least partial surgical resection.
2113
The Potential Routes of Distant Metastasis for Nasopharyngeal Carcinoma
S.H. Cheng, K. Yen, J.J. Jian, S.Y. Tsai, A. Feng, N. Chu, Y. Lin, K. Chan, C. Lin, T. Tan, C. Hsieh, A.T. Huang Radiation Oncology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan Purpose/Objective: We hypothesize that parapharyngeal space venous plexus and marrow of skull base bone are the potential routes for distant metastasis in stage I to III nasopharyngeal carcinoma (NPC). In this report, we used two sets of data to validate our hypothesis. Materials/Methods: Five hundreds and one (501) patients with NPC were enrolled in this study. Selection criteria are stage I-IVA-B patients who had primary irradiation and MRI as head and neck tumor evaluation in our hospital between 1990 and 2001. Patients who had radiation dose less than 60 Gy, and/or pre-radiation chemotherapy in outside hospital were excluded. If our hypothesis is true for patients with stage I-III without PPSE and bone invasion (T3), the risk of distant metastasis would be very low no matter whether patients receive adjuvant chemotherapy or not. Results: Of 147 patients treated between 1990 and 1997, 47 patients were stage I-III without PPSE and T3 disease and usually were treated with CCRT followed by adjuvant chemotherapy. No distant metastasis was observed in a median follow-up interval of 74 months. Of 354 patients treated after 1998, 95 patients were stage I-III patients without PPSE and T3 disease (67% were treated without adjuvant chemotherapy). The risk of developing distant metastasis is only 3% after a median follow-up 27 months. Among three patients developing distant metastases, one had a controversial interpretation of PPSE between radiologists, and one had been given neck excision biopsy before referral to our hospital. Conclusions: Our observation suggests that the risk of distant metastasis in stage I-III NPC patients without PPSE and T3 is very low. Parapharyngeal space venous plexus and marrow of skull base bone are the potential routes for hematogenous spreading in stage I-III NPC. Hematogenous spreading through neck lymph node is uncommon until neck lymph node size is greater than 6 cm or supraclavicular lymph node has been involved (N3 disease).
2114
The Clinical Usefulness of Post-treatment FDG-PET for Prediction of Prognosis in Lung Cancer Patients Treated with Radiation Therapy
Y. Nakayama, Y. Kitamoto, H. Ishikawa, J. Saitoh, H. Sakurai, T. Akimoto, M. Hasegawa, T. Nakano Radiology & Radiation Oncology, Gunma University, Maebashi, Japan Purpose/Objective: In lung cancer patients, FDG-PET is the most reliable modality in staging diagnosis and treatment planning. But the clinical usefulness of FDG-PET is still controversial in the prediction and assessment of response of radiation therapy. The timing of FDG study is also confusing. A high FDG uptake immediately after therapy due to the effect of radiation or unknown causes has been noted. In some reports, the timing of 3 or 6 months after treatment was recommended. But it is too late to consider the adjuvant therapy and to distinguish the response of radiation therapy from local recurrence. So we set the timing of evaluation approximately 4 weeks after treatment. The purpose of this study is to clarify the role of FDG-PET
Proceedings of the 45th Annual ASTRO Meeting
in lung cancer to evaluate the therapeutic effect of radiation therapy in predicting prognosis and to investigate the timing of FDG-PET after treatment. Materials/Methods: Twenty-five lung cancer patients treated with definitive radiation therapy were included in this study. Twenty-nine sites including 25 primary tumors (one patient had double cancer) and 4 lymph nodes were estimated. By histologic type, 20 patients consisted of squamous cell carcinoma. All patients underwent FDG-PET at around 4 weeks (range from 4 weeks to 8 weeks, mean 4.7 weeks) after completion of radiation therapy. The median follow-up was 10 months (ranged from 5 to 23 months). Standard uptake value (SUV) was used as an index of the FDG uptake. Results: Among 29 sites, 7 sites had local relapse. On post-treatment FDG-PET, 14 out of 29 sites showed decrease in the SUVs below 2.0 and all of them are free from tumor. In contrast, 15 sites in SUVs over 2.0 on post-treatment FGD-PET showed local relapse in 7 sites. The progression-free survival of 15 sites in SUVs over 2.0 was 67% at 6 months and 47% at 12 months. Three patients had mild FDG uptake at the area of radiation pneumonia. From the shape of FDG uptake at the area of radiation pneumonia, there was no confusion in assessing tumor response. Conclusions: These results indicate that recommended interval between FDG-PET and completion of radiation therapy is approximately 4 weeks, and FDG uptake after radiation therapy would have a prognostic significance in lung cancer patients.
2115
Gender, Limited Stage Small Cell Lung Cancer and the Experience of Concurrent Chemoradiation 1
G. Videtic, L. Stitt,2 F. Whiston2 1
Radiation Oncology, Cleveland Clinic Foundation, Cleveland, OH, 2Biometry, London Regional Cancer Centre, London, ON, Canada Purpose/Objective: Female sex is considered a positive prognostic factor when it comes to small cell lung cancer (SCLC) survival. To explore the basis for this finding, a retrospective review was carried out to determine whether the sex of patients (pts) receiving concurrent chemotherapy (ChT) and radiotherapy (RT) for limited stage SCLC (LSCLC) is associated with differences in treatment-related toxicity rates, failure patterns and survival. Materials/Methods: From 1989 to 1999, 215 LSCLC pts received 6 cycles of alternating cyclophosphamide/adriamycin/ vincristine and etoposide/cisplatin (EP), as per a NCI-Canada randomized trial “best arm”. Thoracic RT started with EP only (cycle 2 or 3) and was: 40 Gy/15 fractions/3 weeks or 50 Gy/25 fractions/5 weeks. RT fields encompassed gross and microscopic disease with 2-cm margins. Prophylactic cranial irradiation was administered to complete responders following re-staging at the discretion of the clinician. RT interruptions during concurrent ChT⫹RT were recorded as number of days and used as the “marker” for treatment toxicity. Smoking status at treatment start was recorded for all known smokers. Results: At the time of analysis, 23 pts (10.7%) were alive and 192 (89.3%) dead. Overall survival (OS) for all pts at 2 and 5 years was 22.7% and 7.2%, respectively, with median survival of 14.7 months. 126 LSCLC pts (58.6%) were men and 89 (48.4%) women. Smoking status at treatment start was recorded for 186 pts (86.5%): 107 (58%) not smoking [76 (71%) male; 31 (29%) female] and 79 (42%) smoking [36 (46%) male; 43 (54%) female] (male vs female, p⫽0.0005). There were otherwise no significant differences between the 2 groups over a range of patient- and treatment-related variables. 56 pts (26%) had treatment breaks for toxicity, for a median length of 5 days (range 1-18). The incidence of RT breaks was not related to gender (p⫽0.95). OS at 2- and 5-years were greater for women than men [30%;12.5% vs 18%;2.5%, respectively](p⫽0.07). Table 1 provides survival results according to sex, use of RT breaks and smoking status during treatment. Looking at sex and treatment interruptions: women without treatment breaks do the best, men with breaks the worst (p⫽0.002). A woman with a delay does as well as a man without. Looking at smoking status and sex: continued smoking decreases a woman’s survival (p⫽0.01). Overall, women survive longer than men irrespective of their smoking status. Males continuing to smoke on treatment did the poorest (p⫽0.005). Sites of first relapse were recorded in 132 cases (61%). Chest failures were greater in men (45%) than women (35%), with brain failure rates equivalent. Multivariable analysis of prognostic factors including smoking revealed positive benefit to female sex (HR⫽0.66; 95%CI (0.48,0.92), p⫽0.014). Conclusions: Female LSCLC patients treated with concurrent RT⫹ChT tolerated treatment as well as men but overall had better survival. Whether or not a woman smoked or experienced treatment interruptions, she survived longer than her male counterpart. Failure patterns suggested poorer control in the chest in men than women. The results suggest an intrinsic biological basis for the improved survival of women with SCLC.
S411