- Email: [email protected]
Esophagitis Identified in Restaging FDG-PET after Radiotherapy or Chemo-radiotherapy in Lung Cancer
Proceedings of the 50th Annual ASTRO Meeting Materials/Methods: All evaluable, archived 3-D treatment plans for patients with registered outcomes treated for NSCLC between 1991 and 2001 were eligible. RP which resulted in steroid use or more intensive intervention was classified as an event (WUSTL Grade 2 or higher; RTOG Grade 3 or higher). Doses were retrospectively corrected for heterogeneity effects via a Monte Carlobased method. Plans were processed and reviewed using CERR (computational environment for radiotherapy research). Heart volumes were re-contoured within CERR by a single physician (n = 209, with 48 RP events). The structure of bronchi in lung for each available patient was auto-contoured using active contour methods implemented in the ITK-SNAP software package. Heart and normal lung (lung minus gross tumor volume) dose-volume parameters were extracted for further modeling using CERR. Evaluated factors included clinical (age, gender, race, performance status, weight loss, smoking, histology); dosimetric parameters for heart (D5-D100, V10-V80, mean dose, maximum dose, and minimum dose); treatment factors (chemotherapy, treatment time, fraction size); and location parameters (heart-center-of-dose, sup-inf within the heart; GTV location within the lung). Dose-volume parameters were also separately extracted for bronchial vs. non-bronchial normal lung regions. The best model order was determined using leave-one-out cross validation. The best multivariate model was obtained by step-wise variable selection and logistic regression. Results: Leave-one-out cross validation analysis supported a model order of four variables (with rank correlation coefficients on the out-of-sample points of about 0.31). The most commonly selected variables were (in order of decreasing frequency): heart D10 (minimum dose to the hottest 10%), heart D30, bronchi V80, and non-bronchi V20. Conclusions: Although heart dose-volume parameters were more statistically significant, the RP risk model improved by including bronchial and non-bronchial dose-volume parameters separately. A high-dose bronchial irradiation term frequently was selected, indicating that RP-risk may be increased when bronchi are irradiated to relatively high doses. These correlations should be tested further against new datasets. Supported by NIH grant CA85181. Author Disclosure: E.X. Huang, None; J.D. Bradley, None; M. Trovo, None; Y. Mu, None; I. El Naqa, None; A. Apte, None; D. Khullar, None; J.O. Deasy, NIH R01 CA85181, B. Research Grant; Tomotherapy, Inc., B. Research Grant; Varian Corp., B. Research Grant.
2635
Concurrent Chemoradiotherapy in Locally Advanced Non-small Cell Lung Cancer: Comparison of Two Treatment Regimens
M. Leclerc1, B. Raby2, F. Laberge2, B. Fournier2, S. Martin2, Y. Lacasse2 1 De´partement de Radio-Oncologie, Hoˆtel-Dieu de Que´bec, Centre Hospitalier Universitaire de Que´bec (CHUQ), Que´bec, QC, Canada, 2Clinique d’Oncologie Ambulatoire, Centre de Pneumologie, Hoˆpital Laval, Institut Universitaire de Cardiologie et de Pneumologie de l’Universite´ Laval, Que´bec, QC, Canada
Purpose/Objective(s): The primary objective was to compare overall survival and secondary objectives were to examine failurefree survival, response rates and toxicity between two regimens of concurrent chemo-radiotherapy (CALGB 9431 and SWOG S9504). Materials/Methods: We conducted a retrospective analysis of all patients treated with either protocol in our institution from November 2004 to September 2007. CALGB 9431 consisted of cisplatin and vinorelbine given as induction followed by concomitant chemoradiotherapy. SWOG S9504 consisted of cisplatin and etoposide given concomitantly with radiotherapy followed by consolidation docetaxel. Results: 28 patients were treated with CALGB 9431 and 53 with SWOG S9504; 68 patients contributed to the analysis (20 in CALGB 9431 and 48 in SWOG S9504). The two groups were similar in age, gender, stage, histology, weight loss and comorbidities at the time of diagnosis. Median follow-up in CALGB 9431 and SWOG S9504 was 20 and 11 months, respectively. There were significantly more partial responses in SWOG S9504 (70% vs. 40%). However, we did not observe significant differences in 2-year overall survival (CALBG 9431: 50% vs. SWOG S9504: 53%; log-rank test, p = 0.92) and failure-free survival (CALGB 9431: 15% vs. SWOG S9504: 31%; log-rank test, p = 0.88). Severe neutropenia occurred more frequently in CALGB 9431 (74% vs. 13%; p \ 0.0001). Other toxicities were similar between the two groups. Conclusions: Patients treated with immediate concurrent therapy (SWOG S9504) had more partial responses but this did not translate into survival benefits. Severe neutropenia occurred more frequently with CALBG 9431. Other toxicities were similar between the two groups. Author Disclosure: M. Leclerc, None; B. Raby, None; F. Laberge, None; B. Fournier, None; S. Martin, None; Y. Lacasse, None.
2636
Esophagitis Identified in Restaging FDG-PET after Radiotherapy or Chemo-radiotherapy in Lung Cancer
T. T. Chun, A. J. Fischman, M. Ancukiewicz, A. Niemierko, P. M. Fidias, T. J. Lynch, N. C. Choi Massachusetts General Hospital, Boston, MA Purpose/Objective(s): Acute esophagitis is one of the most common side effects among lung cancer patients treated with highdose radiotherapy (RT) or radiotherapy combined with chemotherapy (CRT). The objective evaluation of patients with such treatment-induced esophagitis remains a challenge to clinicians, since the diagnosis and management are based largely on patients’ symptoms and their clinical history. In this study, we explored the utility of restaging FDG-PET as an objective means to identify treatment-induced esophagitis. Materials/Methods: FDG-PET scans were performed prior to, 10-14 days and 3 months after the completion of RT or CRT as a part of on-going Partners Protocol 03-282. These scans were analyzed (1) qualitatively by trained observers using a visual score system and (2) quantitatively using the Standard Uptake Value (SUV) method corrected for weight. Detailed patient reports including full clinical history and self-reported surveys on their graded esophageal symptom scales from 0 to 10 were reviewed. Subsequently, the patients with esophageal symptoms were grouped according to the Common Terminology Criteria for Adverse Events (CTCAE). Results: Of the 89 lung cancer patients entered into the study, 43 patients (48%) reported esophageal symptoms. Of these 43, 40 patients showed increased FDG uptake 10-14 days after the completion of RT or CRT, and only 15 patients showed persistent
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uptake at 3 months post RT or CRT. Patients with grade 1 esophagitis (n = 22) had an average SUV of 2.53; grade 2 (n = 10) 2.89; grade 3 (n = 11) 2.70. Patients with no esophagitis (n = 46) had an average SUV of 1.81. Correlation coefficients (R) between qualitative visual scores vs. SUVs, CTCAE grades, and survey pain scores were 0.77, 0.67, and 0.57 respectively. Conclusions: Restaging FDG-PET performed 10-14 days after the completion of RT or CRT for tumor response could be an objective way to identify treatment-induced esophagitis. Poor correlation was noted between survey pain scores and qualitative visual scores of FDG-PET. Quantitative analysis of FDG-PET may provide additional information on the location and severity of esophagitis that would be useful for its clinical management. Author Disclosure: T.T. Chun, None; A.J. Fischman, None; M. Ancukiewicz, None; A. Niemierko, None; P.M. Fidias, None; T.J. Lynch, None; N.C. Choi, None.
2637
Low Morbidity and Excellent Local Control using Image Guided Stereotactic Body Radiotherapy (IGSBRT) for Lung Tumors
N. K. Sharma1, K. Ruth1, A. A. Konski1, M. K. Buyyounouski1, N. Nicolaou1, B. E. Lally1, J. Q. Yu1, C. J. Langer1, B. Movsas2, S. J. Feigenberg1 1
Fox Chase Cancer Center, Philadelphia, PA, 2Henry Ford Cancer Center, Detroit, MI
Purpose/Objective(s): Stereotactic body radiotherapy is widely used as an alternative to surgery for lung tumors. Currently, grade $3 morbidity rates have been reported as the primary dose limiting constraints. Reports are mixed regarding local control rates and accuracy of FDG-PET in demonstrating effectiveness. This study reports the results of the Fox Chase Cancer Center (FCCC) IGSBRT experience for lung tumors and investigates FDG-PET utility in assessing response. Materials/Methods: From 4/2004 to 9/2007, 47 patients with biopsy proven lung cancer received IGSBRT. Patients with metastatic disease or central lesions were included. FDG-PET was performed in definitively treated patients pre- and 3 months posttreatment. Internal Target Volumes (ITV) were determined by fusion of 3 non-gated CT scans (free-breathing, maximal expiration and inspiration), or 4-D CT simulation. ITVs were expanded by 5mm in all directions to generate planning target volumes (PTV). Dosimetric optimization was performed to ensure 100% PTV coverage (usually prescribed to the 90% isodose line), using 7-9 noncoplanar beam arrangements. As dose and fractionation varied, biologically equivalent doses (BED) were calculated using the equation BED = nd (1 + d/[a/b]) where n = total number of fractions, d = dose per fraction, and a/b = 10. Daily pre-treatment localization was performed by CT-on-rails or cone-beam CT. Toxicities were scored by RTOG common toxicity criteria. Results: Mean follow-up was 17 months (1.3- 43.8). Patients were evenly distributed with respect to gender (24 female, 23 male) and histology (24 adeno/BAC, 23 squamous/other). BED was \100 Gy in 13 and .100 Gy in 34 patients (median 105.6 Gy). The most common regimen was 48 Gy in 4 fractions (n = 27). Six treated lesions were metastatic in origin and 41 were lung primaries. Mean tumor size was 2.2 cm (0.3-4.5). Local control at 12 and 18 months was 97% and 93%, respectively. There were only 6 local failures. Only 1 patient had Grade $3 toxicity (tri-lobar pneumonia diagnosed 2 days posttreatment). Three others had grade 1 symptomatic toxicity, which resolved spontaneously. There were no late toxicities. No significant covariates (age, tumor size, lobar location, histology, smoking status, gender or BED) predicted for local control or morbidity. Twenty-three of the 26 patients with a pre- and 3 month post- treatment PET/CT, showed decreased activity on the posttreatment PET/CT. Mean percentage decrease in maximal SUV was greater among patients with local control compared with those that failed (55% vs. 22%; p = 0.07). Conclusions: IGSBRT at FCCC is associated with very low morbidity. Our results suggest that greater decrease in FDG-PET SUV by 3 months may be associated with improved local control and may be used as an early surrogate of local failure. Author Disclosure: N.K. Sharma, None; K. Ruth, None; A.A. Konski, None; M.K. Buyyounouski, None; N. Nicolaou, None; B.E. Lally, None; J.Q. Yu, None; C.J. Langer, None; B. Movsas, None; S.J. Feigenberg, None.
2638
Absent from the Dose Volume Histogram: Dose Rate and Fraction Size to Normal Lung with IMRT Planning for NSCLC
C. Murphy1, N. Kuritzky1, P. Morgan2, S. Li1, C. Miyamoto1 1
Temple University Hospital, Philadelphia, PA, 2Fox Chase Cancer Center, Philadelphia, PA
Purpose/Objective(s): Models estimating the risk of radiation pneumonitis have traditionally focused on dose-volume relationships based on planning that employed AP/PA fields followed by off-cord obliques. As such, the dose rate and dose per fraction are often similar for the PTV and irradiated tissue outside of the PTV. When patients are treated daily with 4 or more conformal fields, fraction size to normal tissues can be significantly decreased- and with IMRT- the dose rate can diminish substantially. We examined the dose per fraction and dose rate to normal lung outside the PTV in patients who received dose escalated IMRT for lung cancer. Materials/Methods: We reviewed plans and treatment times of 12 sequential patients treated with IMRT for stage III lung cancer to doses between 70 and 74 Gy. Treatment was delivered with a step and shoot technique on the Elekta Synergy Platform. Treatment times were recorded prospectively. Dose per fraction and dose rate were calculated for several dose/volume points associated with pneumonitis including the V15, 20, 30. The equivalent dose in 2 Gy /fraction (EQD 2 Gy) for late effects at these dose/volume points was calculated using an a/b = 3. Results: Treatment delivery for lung IMRT averaged 17 minutes. The dose rate to the V15, 20, 30 averaged 2.41, 3.23, 4.82 cGy/ minute respectively, whereas the dose/fraction averaged 41,55, and 82 cGy, respectively. The EQD2 for late effects at this fractionation was calculated at 10.2, 14.2, and 22.9 Gy, respectively. Conclusions: Plans which call for all fields to be treated daily, rather than sequential AP/PA fields followed by obliques allow for lower doses per faction to tissue outside of the PTV. In addition, IMRT results in substantially reduced dose rates to significant portions of normal lung. Fraction size and dose rate are both known to influence pulmonary toxicity. With total body irradiation (TBI), dose rates of less than 10-12 cGy/minute are known to reduce rates of pneumonitis, while fibroblasts in vitro exposed to 3-6 cGy/minute exhibit a dose rate reduction factor of around 1.5. With IMRT, dose rates to critical dose/volume parameters fall well within this range. Future modeling of pneumonitis may need to account for both treatment technique and time. Author Disclosure: C. Murphy, None; N. Kuritzky, None; P. Morgan, None; S. Li, None; C. Miyamoto, None.
2635
Concurrent Chemoradiotherapy in Locally Advanced Non-small Cell Lung Cancer: Comparison of Two Treatment Regimens
M. Leclerc1, B. Raby2, F. Laberge2, B. Fournier2, S. Martin2, Y. Lacasse2 1 De´partement de Radio-Oncologie, Hoˆtel-Dieu de Que´bec, Centre Hospitalier Universitaire de Que´bec (CHUQ), Que´bec, QC, Canada, 2Clinique d’Oncologie Ambulatoire, Centre de Pneumologie, Hoˆpital Laval, Institut Universitaire de Cardiologie et de Pneumologie de l’Universite´ Laval, Que´bec, QC, Canada
Purpose/Objective(s): The primary objective was to compare overall survival and secondary objectives were to examine failurefree survival, response rates and toxicity between two regimens of concurrent chemo-radiotherapy (CALGB 9431 and SWOG S9504). Materials/Methods: We conducted a retrospective analysis of all patients treated with either protocol in our institution from November 2004 to September 2007. CALGB 9431 consisted of cisplatin and vinorelbine given as induction followed by concomitant chemoradiotherapy. SWOG S9504 consisted of cisplatin and etoposide given concomitantly with radiotherapy followed by consolidation docetaxel. Results: 28 patients were treated with CALGB 9431 and 53 with SWOG S9504; 68 patients contributed to the analysis (20 in CALGB 9431 and 48 in SWOG S9504). The two groups were similar in age, gender, stage, histology, weight loss and comorbidities at the time of diagnosis. Median follow-up in CALGB 9431 and SWOG S9504 was 20 and 11 months, respectively. There were significantly more partial responses in SWOG S9504 (70% vs. 40%). However, we did not observe significant differences in 2-year overall survival (CALBG 9431: 50% vs. SWOG S9504: 53%; log-rank test, p = 0.92) and failure-free survival (CALGB 9431: 15% vs. SWOG S9504: 31%; log-rank test, p = 0.88). Severe neutropenia occurred more frequently in CALGB 9431 (74% vs. 13%; p \ 0.0001). Other toxicities were similar between the two groups. Conclusions: Patients treated with immediate concurrent therapy (SWOG S9504) had more partial responses but this did not translate into survival benefits. Severe neutropenia occurred more frequently with CALBG 9431. Other toxicities were similar between the two groups. Author Disclosure: M. Leclerc, None; B. Raby, None; F. Laberge, None; B. Fournier, None; S. Martin, None; Y. Lacasse, None.
2636
Esophagitis Identified in Restaging FDG-PET after Radiotherapy or Chemo-radiotherapy in Lung Cancer
T. T. Chun, A. J. Fischman, M. Ancukiewicz, A. Niemierko, P. M. Fidias, T. J. Lynch, N. C. Choi Massachusetts General Hospital, Boston, MA Purpose/Objective(s): Acute esophagitis is one of the most common side effects among lung cancer patients treated with highdose radiotherapy (RT) or radiotherapy combined with chemotherapy (CRT). The objective evaluation of patients with such treatment-induced esophagitis remains a challenge to clinicians, since the diagnosis and management are based largely on patients’ symptoms and their clinical history. In this study, we explored the utility of restaging FDG-PET as an objective means to identify treatment-induced esophagitis. Materials/Methods: FDG-PET scans were performed prior to, 10-14 days and 3 months after the completion of RT or CRT as a part of on-going Partners Protocol 03-282. These scans were analyzed (1) qualitatively by trained observers using a visual score system and (2) quantitatively using the Standard Uptake Value (SUV) method corrected for weight. Detailed patient reports including full clinical history and self-reported surveys on their graded esophageal symptom scales from 0 to 10 were reviewed. Subsequently, the patients with esophageal symptoms were grouped according to the Common Terminology Criteria for Adverse Events (CTCAE). Results: Of the 89 lung cancer patients entered into the study, 43 patients (48%) reported esophageal symptoms. Of these 43, 40 patients showed increased FDG uptake 10-14 days after the completion of RT or CRT, and only 15 patients showed persistent
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uptake at 3 months post RT or CRT. Patients with grade 1 esophagitis (n = 22) had an average SUV of 2.53; grade 2 (n = 10) 2.89; grade 3 (n = 11) 2.70. Patients with no esophagitis (n = 46) had an average SUV of 1.81. Correlation coefficients (R) between qualitative visual scores vs. SUVs, CTCAE grades, and survey pain scores were 0.77, 0.67, and 0.57 respectively. Conclusions: Restaging FDG-PET performed 10-14 days after the completion of RT or CRT for tumor response could be an objective way to identify treatment-induced esophagitis. Poor correlation was noted between survey pain scores and qualitative visual scores of FDG-PET. Quantitative analysis of FDG-PET may provide additional information on the location and severity of esophagitis that would be useful for its clinical management. Author Disclosure: T.T. Chun, None; A.J. Fischman, None; M. Ancukiewicz, None; A. Niemierko, None; P.M. Fidias, None; T.J. Lynch, None; N.C. Choi, None.
2637
Low Morbidity and Excellent Local Control using Image Guided Stereotactic Body Radiotherapy (IGSBRT) for Lung Tumors
N. K. Sharma1, K. Ruth1, A. A. Konski1, M. K. Buyyounouski1, N. Nicolaou1, B. E. Lally1, J. Q. Yu1, C. J. Langer1, B. Movsas2, S. J. Feigenberg1 1
Fox Chase Cancer Center, Philadelphia, PA, 2Henry Ford Cancer Center, Detroit, MI
Purpose/Objective(s): Stereotactic body radiotherapy is widely used as an alternative to surgery for lung tumors. Currently, grade $3 morbidity rates have been reported as the primary dose limiting constraints. Reports are mixed regarding local control rates and accuracy of FDG-PET in demonstrating effectiveness. This study reports the results of the Fox Chase Cancer Center (FCCC) IGSBRT experience for lung tumors and investigates FDG-PET utility in assessing response. Materials/Methods: From 4/2004 to 9/2007, 47 patients with biopsy proven lung cancer received IGSBRT. Patients with metastatic disease or central lesions were included. FDG-PET was performed in definitively treated patients pre- and 3 months posttreatment. Internal Target Volumes (ITV) were determined by fusion of 3 non-gated CT scans (free-breathing, maximal expiration and inspiration), or 4-D CT simulation. ITVs were expanded by 5mm in all directions to generate planning target volumes (PTV). Dosimetric optimization was performed to ensure 100% PTV coverage (usually prescribed to the 90% isodose line), using 7-9 noncoplanar beam arrangements. As dose and fractionation varied, biologically equivalent doses (BED) were calculated using the equation BED = nd (1 + d/[a/b]) where n = total number of fractions, d = dose per fraction, and a/b = 10. Daily pre-treatment localization was performed by CT-on-rails or cone-beam CT. Toxicities were scored by RTOG common toxicity criteria. Results: Mean follow-up was 17 months (1.3- 43.8). Patients were evenly distributed with respect to gender (24 female, 23 male) and histology (24 adeno/BAC, 23 squamous/other). BED was \100 Gy in 13 and .100 Gy in 34 patients (median 105.6 Gy). The most common regimen was 48 Gy in 4 fractions (n = 27). Six treated lesions were metastatic in origin and 41 were lung primaries. Mean tumor size was 2.2 cm (0.3-4.5). Local control at 12 and 18 months was 97% and 93%, respectively. There were only 6 local failures. Only 1 patient had Grade $3 toxicity (tri-lobar pneumonia diagnosed 2 days posttreatment). Three others had grade 1 symptomatic toxicity, which resolved spontaneously. There were no late toxicities. No significant covariates (age, tumor size, lobar location, histology, smoking status, gender or BED) predicted for local control or morbidity. Twenty-three of the 26 patients with a pre- and 3 month post- treatment PET/CT, showed decreased activity on the posttreatment PET/CT. Mean percentage decrease in maximal SUV was greater among patients with local control compared with those that failed (55% vs. 22%; p = 0.07). Conclusions: IGSBRT at FCCC is associated with very low morbidity. Our results suggest that greater decrease in FDG-PET SUV by 3 months may be associated with improved local control and may be used as an early surrogate of local failure. Author Disclosure: N.K. Sharma, None; K. Ruth, None; A.A. Konski, None; M.K. Buyyounouski, None; N. Nicolaou, None; B.E. Lally, None; J.Q. Yu, None; C.J. Langer, None; B. Movsas, None; S.J. Feigenberg, None.
2638
Absent from the Dose Volume Histogram: Dose Rate and Fraction Size to Normal Lung with IMRT Planning for NSCLC
C. Murphy1, N. Kuritzky1, P. Morgan2, S. Li1, C. Miyamoto1 1
Temple University Hospital, Philadelphia, PA, 2Fox Chase Cancer Center, Philadelphia, PA
Purpose/Objective(s): Models estimating the risk of radiation pneumonitis have traditionally focused on dose-volume relationships based on planning that employed AP/PA fields followed by off-cord obliques. As such, the dose rate and dose per fraction are often similar for the PTV and irradiated tissue outside of the PTV. When patients are treated daily with 4 or more conformal fields, fraction size to normal tissues can be significantly decreased- and with IMRT- the dose rate can diminish substantially. We examined the dose per fraction and dose rate to normal lung outside the PTV in patients who received dose escalated IMRT for lung cancer. Materials/Methods: We reviewed plans and treatment times of 12 sequential patients treated with IMRT for stage III lung cancer to doses between 70 and 74 Gy. Treatment was delivered with a step and shoot technique on the Elekta Synergy Platform. Treatment times were recorded prospectively. Dose per fraction and dose rate were calculated for several dose/volume points associated with pneumonitis including the V15, 20, 30. The equivalent dose in 2 Gy /fraction (EQD 2 Gy) for late effects at these dose/volume points was calculated using an a/b = 3. Results: Treatment delivery for lung IMRT averaged 17 minutes. The dose rate to the V15, 20, 30 averaged 2.41, 3.23, 4.82 cGy/ minute respectively, whereas the dose/fraction averaged 41,55, and 82 cGy, respectively. The EQD2 for late effects at this fractionation was calculated at 10.2, 14.2, and 22.9 Gy, respectively. Conclusions: Plans which call for all fields to be treated daily, rather than sequential AP/PA fields followed by obliques allow for lower doses per faction to tissue outside of the PTV. In addition, IMRT results in substantially reduced dose rates to significant portions of normal lung. Fraction size and dose rate are both known to influence pulmonary toxicity. With total body irradiation (TBI), dose rates of less than 10-12 cGy/minute are known to reduce rates of pneumonitis, while fibroblasts in vitro exposed to 3-6 cGy/minute exhibit a dose rate reduction factor of around 1.5. With IMRT, dose rates to critical dose/volume parameters fall well within this range. Future modeling of pneumonitis may need to account for both treatment technique and time. Author Disclosure: C. Murphy, None; N. Kuritzky, None; P. Morgan, None; S. Li, None; C. Miyamoto, None.