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Impact of Subventricular Zone (SVZ) Irradiation on Outcome of Patients With Glioblastoma Multiforme
Volume 96 Number 2S Supplement 2016
2156 The Usefulness of Apparent Diffusion Coefficient Maps in the Evaluation of Radiation Therapy for Primary Central Nerve System Lymphoma R. Mikami,1 Z. Amar,2 T. Itonaga,1 S. Shiraishi,1 M. Okubo,1 H. Nakayama,1 S. Sugahara,3 and K. Tokuuye1; 1Tokyo Medical University Hospital, Tokyo, Japan, 2department of Radiology, Tokyo Medical University, Tokyo, Japan, 3Ibaraki Medical Center, Ibaraki, Japan Purpose/Objective(s): We retrospectively evaluated the usefulness of apparent diffusion coefficient (ADC) maps in the treatment of radiation therapy (RT) for primary central nerve system lymphoma (PCNSL) as an early response indicator. Materials/Methods: Between January 2012 and January 2015, eight consecutive patients with PCNSL who underwent radiation therapy were assessed. The median age was 73 years, ranging from 49 to 86, and five were males and three females. All patients were histologically confirmed as having diffuse large B-cell lymphoma. A median radiation dose of 45 Gy (45 - 50) in 25 sessions with a daily dose of 1.8 e 2.0 Gy was delivered using 3-D conformal radiation therapy. All patients underwent chemotherapy of a high dose methotrexate before performing RT. To evaluate treatment response, tumors were contoured on the MRI prior to biopsy by one radiologist and one radiation oncologist. ADC histogram parameters were given within the contour. The skewness and kurtosis of ADC in relation to overall survival and progression free survival were assessed among other possible predictive factors, including median values of minimum, maximum, and mode of ADC maps. Results: Median observation time was 5 months (range 1-28 months), and 3 patients were observed over 19 months. One to three months after RT, 2 patients (25%) showed a complete response, 5 patients (63%) showed a partial response and 1 patient (13%) showed no change in tumor size when evaluated using the response evaluation criteria for solid tumors. The median values of minimum, maximum, median, mode, skewness and kurtosis of ADC were 536.5, 2500, 955.5, 1250, 1.03 and 0.75, respectively. The progression-free survival rate was statistically significantly higher in patients who had a higher minimum ADC value (P Z 0.017), a lower maximum ADC value (P Z 0.017), a lower kurtosis (P Z 0.025) and a lower skewness (P Z 0.025). No other significant relationship was found in any ADC histogram parameters or overall survival rates. Conclusion: ADC histogram parameters were useful as a biomarker for predicting the outcome of RT for PCNSL. Author Disclosure: R. Mikami: None. Z. Amar: None. T. Itonaga: None. S. Shiraishi: None. M. Okubo: None. H. Nakayama: None. S. Sugahara: None. K. Tokuuye: None.
2157 Impact of Subventricular Zone (SVZ) Irradiation on Outcome of Patients With Glioblastoma Multiforme B.S. Mathew,1 S.B. Kaliyath,1 J. Krishnan,1 and S. Bhasi2; 1Regional Cancer Centre, Trivandrum, India, 2Regional Cancer Centre, Thiruvananthapuram, India Purpose/Objective(s): Glioblastoma Multiforme (GBM) is characterized by early relapse and mortality in spite of multi-modality treatments. It is postulated that treatment resistance is an inherent characteristic exhibited by pro-genitor neoplastic cells that reside primarily in the SVZ. Treatment directed at these cells could potentially improve results. Published results of studies assessing impact of ipsilateral and contra-lateral SVZ radiation doses have been inconsistent. This retrospective study was conducted to assess the correlation of SVZ doses and survival in patients with GBM treated curatively. Materials/Methods: Forty-seven patients with histologically proven GBM treated with radical radiation therapy, concurrent and adjuvant Temozolomide therapy and whose dosimetry data were available were included. Median age was 52 years. Median radiation therapy dose prescribed was 59.4 Gy. All patients completed the planned radiation therapy with concurrent Temozolomide. Thirty four patients received 6 cycles of adjuvant
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Temozolomide. The ipsilateral and contralateral SVZs were delineated on co-registered MRI-CT images as a 5-mm margin along the lateral wall of the lateral ventricles. The mean ipsilateral, contralateral and bilateral SVZ doses were 56.3 Gy (range 33-63 Gy), 50.4 Gy (range 23-79 Gy) and 52 Gy (28-69 Gy). The study end-points of PFS and OS were calculated from the date of surgery to the date of radiologic and/or clinical progression and death/last follow up respectively. Age, performance status, extent of surgical resection, ipsilateral and contralateral SVZ doses, and number of adjuvant chemotherapy cycles were assessed for prognostic significance. Survival probability was estimated using the Kaplan-Meier method. Log rank test was used to test the significance between groups. Cox proportional hazards analyses were used to identify prognostic factors. Results: At median follow up of 19 months (range 3- 46 months) all patients had relapsed. Most recurrences were infield (n Z 39). The median PFS and OS were 17 and 19 months. The PFS and OS at two years were 36.2% and 21.3% respectively. Patients who received ipsilateral SVZ dose of 56 Gy appeared to have better but non-significant median PFS (17 vs 15 months; P Z 0.178) and OS (19 vs 17 months; P Z 0.101). Patients receiving contralateral SVZ doses 50 Gy showed similar trend; (median PFS: 17 vs 12 months; P Z 0.121), (median OS 21 vs 15 months; P Z 0.141). On univariate analysis, only the number of adjuvant Temozolomide cycles showed prognostic impact. Conclusion: This retrospective study including a small number of patients indicated a trend towards improved - albeit non-significant- survival for patients who received higher dose to the ipsilateral and contralateral SVZ. A well-designed prospective randomized study is required to identify patients who would benefit from intentional SVZ targeting. Author Disclosure: B. Mathew: None. S.B. Kaliyath: None. J. Krishnan: None. S. Bhasi: None.
2158 Clustering of Patients With GBM on Treatment Response Reveals Underlying Phenotypic Differences C. Rayfield,1 F. Grady,2 P. Jackson,2 B.R. Bendok,3 S. Vora,4 and K. Swanson2; 1Department of Radiation Oncology, Mayo Clinic Arizona, Scottsdale, AZ, 2Department of Neurological Surgery, Mayo Clinic Arizona, Scottsdale, AZ, 3Mayo Clinic, Phoenix, AZ, 4Mayo Clinic Arizona, Phoenix, AZ Purpose/Objective(s): Glioblastoma (GBM) is considered to be uniformly aggressive. During this multi-institutional retrospective study, the authors sought to cluster patients using the machine-learning k-means (KM) algorithm into discrete groups based on their response to standard of care (SOC) treatment; it was then hypothesized that there exists a significant biological difference that manifests in the distinct patient clusters. Materials/Methods: Thirty-nine patients that underwent SOC treatment consisting of maximally safe resection followed by concurrent chemoRT with temozolomide (TMZ) were included. These patients’ tumor velocities were calculated from T1Gd and T2 clinical MRIs. Additionally, we recorded the nadir time, or the amount of time after RT that a negative growth velocity was maintained. The Euclidean distance between one patient and the rest of the cohort was compared in the 8-D space of the following variables: T1Gd/ T2 pre-treatment growth velocity; T1Gd/T2 RT velocity; T1Gd/T2 posttreatment velocity (velocity from the 1st post-radiation scan and the last scan prior to progression); and nadir time on T1Gd/T2. The patients were then clustered into 2 groups through a KM algorithm such that the other patients in the data that are closest to each individual were identified. The conditional probability for belonging to each group was calculated as the fraction of the surrounding patients that belong to one group or the other by minimizing the distance function. Once clustered, significant differences were sought among the above noted metrics and other clinical parameters including: hemispheric localization, diagnostic radius, radius after surgery, radial change from surgery, surgery type, and post-RT radius. Additionally, MGMT (n Z 17) and VEGF immunohistochemistry score (n Z 15) was compared for patients with tissue available.
2156 The Usefulness of Apparent Diffusion Coefficient Maps in the Evaluation of Radiation Therapy for Primary Central Nerve System Lymphoma R. Mikami,1 Z. Amar,2 T. Itonaga,1 S. Shiraishi,1 M. Okubo,1 H. Nakayama,1 S. Sugahara,3 and K. Tokuuye1; 1Tokyo Medical University Hospital, Tokyo, Japan, 2department of Radiology, Tokyo Medical University, Tokyo, Japan, 3Ibaraki Medical Center, Ibaraki, Japan Purpose/Objective(s): We retrospectively evaluated the usefulness of apparent diffusion coefficient (ADC) maps in the treatment of radiation therapy (RT) for primary central nerve system lymphoma (PCNSL) as an early response indicator. Materials/Methods: Between January 2012 and January 2015, eight consecutive patients with PCNSL who underwent radiation therapy were assessed. The median age was 73 years, ranging from 49 to 86, and five were males and three females. All patients were histologically confirmed as having diffuse large B-cell lymphoma. A median radiation dose of 45 Gy (45 - 50) in 25 sessions with a daily dose of 1.8 e 2.0 Gy was delivered using 3-D conformal radiation therapy. All patients underwent chemotherapy of a high dose methotrexate before performing RT. To evaluate treatment response, tumors were contoured on the MRI prior to biopsy by one radiologist and one radiation oncologist. ADC histogram parameters were given within the contour. The skewness and kurtosis of ADC in relation to overall survival and progression free survival were assessed among other possible predictive factors, including median values of minimum, maximum, and mode of ADC maps. Results: Median observation time was 5 months (range 1-28 months), and 3 patients were observed over 19 months. One to three months after RT, 2 patients (25%) showed a complete response, 5 patients (63%) showed a partial response and 1 patient (13%) showed no change in tumor size when evaluated using the response evaluation criteria for solid tumors. The median values of minimum, maximum, median, mode, skewness and kurtosis of ADC were 536.5, 2500, 955.5, 1250, 1.03 and 0.75, respectively. The progression-free survival rate was statistically significantly higher in patients who had a higher minimum ADC value (P Z 0.017), a lower maximum ADC value (P Z 0.017), a lower kurtosis (P Z 0.025) and a lower skewness (P Z 0.025). No other significant relationship was found in any ADC histogram parameters or overall survival rates. Conclusion: ADC histogram parameters were useful as a biomarker for predicting the outcome of RT for PCNSL. Author Disclosure: R. Mikami: None. Z. Amar: None. T. Itonaga: None. S. Shiraishi: None. M. Okubo: None. H. Nakayama: None. S. Sugahara: None. K. Tokuuye: None.
2157 Impact of Subventricular Zone (SVZ) Irradiation on Outcome of Patients With Glioblastoma Multiforme B.S. Mathew,1 S.B. Kaliyath,1 J. Krishnan,1 and S. Bhasi2; 1Regional Cancer Centre, Trivandrum, India, 2Regional Cancer Centre, Thiruvananthapuram, India Purpose/Objective(s): Glioblastoma Multiforme (GBM) is characterized by early relapse and mortality in spite of multi-modality treatments. It is postulated that treatment resistance is an inherent characteristic exhibited by pro-genitor neoplastic cells that reside primarily in the SVZ. Treatment directed at these cells could potentially improve results. Published results of studies assessing impact of ipsilateral and contra-lateral SVZ radiation doses have been inconsistent. This retrospective study was conducted to assess the correlation of SVZ doses and survival in patients with GBM treated curatively. Materials/Methods: Forty-seven patients with histologically proven GBM treated with radical radiation therapy, concurrent and adjuvant Temozolomide therapy and whose dosimetry data were available were included. Median age was 52 years. Median radiation therapy dose prescribed was 59.4 Gy. All patients completed the planned radiation therapy with concurrent Temozolomide. Thirty four patients received 6 cycles of adjuvant
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E65
Temozolomide. The ipsilateral and contralateral SVZs were delineated on co-registered MRI-CT images as a 5-mm margin along the lateral wall of the lateral ventricles. The mean ipsilateral, contralateral and bilateral SVZ doses were 56.3 Gy (range 33-63 Gy), 50.4 Gy (range 23-79 Gy) and 52 Gy (28-69 Gy). The study end-points of PFS and OS were calculated from the date of surgery to the date of radiologic and/or clinical progression and death/last follow up respectively. Age, performance status, extent of surgical resection, ipsilateral and contralateral SVZ doses, and number of adjuvant chemotherapy cycles were assessed for prognostic significance. Survival probability was estimated using the Kaplan-Meier method. Log rank test was used to test the significance between groups. Cox proportional hazards analyses were used to identify prognostic factors. Results: At median follow up of 19 months (range 3- 46 months) all patients had relapsed. Most recurrences were infield (n Z 39). The median PFS and OS were 17 and 19 months. The PFS and OS at two years were 36.2% and 21.3% respectively. Patients who received ipsilateral SVZ dose of 56 Gy appeared to have better but non-significant median PFS (17 vs 15 months; P Z 0.178) and OS (19 vs 17 months; P Z 0.101). Patients receiving contralateral SVZ doses 50 Gy showed similar trend; (median PFS: 17 vs 12 months; P Z 0.121), (median OS 21 vs 15 months; P Z 0.141). On univariate analysis, only the number of adjuvant Temozolomide cycles showed prognostic impact. Conclusion: This retrospective study including a small number of patients indicated a trend towards improved - albeit non-significant- survival for patients who received higher dose to the ipsilateral and contralateral SVZ. A well-designed prospective randomized study is required to identify patients who would benefit from intentional SVZ targeting. Author Disclosure: B. Mathew: None. S.B. Kaliyath: None. J. Krishnan: None. S. Bhasi: None.
2158 Clustering of Patients With GBM on Treatment Response Reveals Underlying Phenotypic Differences C. Rayfield,1 F. Grady,2 P. Jackson,2 B.R. Bendok,3 S. Vora,4 and K. Swanson2; 1Department of Radiation Oncology, Mayo Clinic Arizona, Scottsdale, AZ, 2Department of Neurological Surgery, Mayo Clinic Arizona, Scottsdale, AZ, 3Mayo Clinic, Phoenix, AZ, 4Mayo Clinic Arizona, Phoenix, AZ Purpose/Objective(s): Glioblastoma (GBM) is considered to be uniformly aggressive. During this multi-institutional retrospective study, the authors sought to cluster patients using the machine-learning k-means (KM) algorithm into discrete groups based on their response to standard of care (SOC) treatment; it was then hypothesized that there exists a significant biological difference that manifests in the distinct patient clusters. Materials/Methods: Thirty-nine patients that underwent SOC treatment consisting of maximally safe resection followed by concurrent chemoRT with temozolomide (TMZ) were included. These patients’ tumor velocities were calculated from T1Gd and T2 clinical MRIs. Additionally, we recorded the nadir time, or the amount of time after RT that a negative growth velocity was maintained. The Euclidean distance between one patient and the rest of the cohort was compared in the 8-D space of the following variables: T1Gd/ T2 pre-treatment growth velocity; T1Gd/T2 RT velocity; T1Gd/T2 posttreatment velocity (velocity from the 1st post-radiation scan and the last scan prior to progression); and nadir time on T1Gd/T2. The patients were then clustered into 2 groups through a KM algorithm such that the other patients in the data that are closest to each individual were identified. The conditional probability for belonging to each group was calculated as the fraction of the surrounding patients that belong to one group or the other by minimizing the distance function. Once clustered, significant differences were sought among the above noted metrics and other clinical parameters including: hemispheric localization, diagnostic radius, radius after surgery, radial change from surgery, surgery type, and post-RT radius. Additionally, MGMT (n Z 17) and VEGF immunohistochemistry score (n Z 15) was compared for patients with tissue available.