The Role of RB1 Alteration and 4q12 Amplification in IDH-WT Glioblastoma

Abstract Background Recent studies have identified that glioblastoma IDH-wild-type (GBM IDH-WT) might be comprised of molecular subgroups with distinct prognoses. Therefore, we investigated the correlation between genetic alterations and survival in 282 GBM IDH-WT patients, to identify subgroups with distinct outcomes. Methods We reviewed characteristics of GBM IDH-WT (2009-2019) patients analyzed by next-generation sequencing interrogating 205 genes and 26 rearrangements. Progression-free survival (PFS) and overall survival (OS) were evaluated with the log-rank test and Cox regression models. We validated our results utilizing data from cBioPortal (MSK-IMPACT dataset). Results Multivariable analysis of GBM IDH-WT revealed that treatment with chemoradiation and RB1-mutant status correlated with improved PFS (HR 0.25 p<0.001 and HR 0.47, p=0.002) and OS (HR 0.24 p<0.001 and HR 0.49, p=0.016). In addition, younger age (<55-years) was associated with improved OS. Karnofsky performance status <80 (HR=1.44, p=0.024) and KDR amplification (HR=2.51, p=0.008) were predictors of worse OS. KDR-amplified patients harbored coexisting PDGFRA and KIT amplification (p<0.001) and TP53-mutations (p=0.04). RB1-mutant patients had less frequent CDKN2A/B and EGFR alterations (p<0.001). Conversely, RB1-mutant patients had more frequent TP53 (p<0.001) and SETD2 (p=0.006) mutations. Analysis of the MSK-IMPACT dataset (n=551) validated the association between RB1 mutations and improved PFS (11.0-months vs. 8.7-months, p=0.009) and OS (34.7-months vs. 21.7-months, p=0.016). Conclusions RB1-mutant GBM IDH-WT is a molecular subgroup with improved PFS and OS. Meanwhile, 4q12 amplification (KDR/PDGFRA/KIT) denoted patients with worse OS. Identifying subgroups of GBM IDH-WT with distinct survival is important for optimal clinical trial design, incorporation of targeted therapies, and personalized neuro-oncological care.

Download Full-text

Phase III Study of VCAP-AMP-VECP vs. Biweekly CHOP in Aggressive Adult T-Cell Leukemia-Lymphoma (ATLL): Japan Clinical Oncology Group Study, JCOG9801.

Blood ◽

10.1182/blood.v106.11.812.812 ◽

2005 ◽

Vol 106 (11) ◽

pp. 812-812 ◽

Cited By ~ 1

Author(s):

Kunihiro Tsukasaki ◽

Takuya Fukushima ◽

Atae Utsunomiya ◽

Syuichi Ikeda ◽

Masato Masuda ◽

...

Keyword(s):

Cox Regression ◽

Performance Status ◽

Progression Free Survival ◽

Complete Response ◽

Phase Iii ◽

Rank Test ◽

P Value ◽

Minimization Method ◽

Adult T Cell Leukemia ◽

Non Hodgkin Lymphoma

Abstract Background: In our study for non-Hodgkin lymphoma (NHL) in 1980’s (JCOG8701), human T-lymphotropic virus type-1- associated ATLL was the poorest prognostic subtype in NHL. The complete response (CR) rate was 42%, the median survival time (MST) was 8 months, and the 4-yr overall survival (OS) was 12% (Proc ASCO13:378, 1994). Our previous phase II study (JCOG9303) of G-CSF-supported, dose-intensified multi-agent chemotherapy with VCAP (vincristine, cyclophosphamide, doxorubicin, prednisolone), AMP (doxorubicin, ranimustine, prednisolone) and VECP (vindesine, etoposide, carboplatin, prednisolone) with intrathecal prophylaxis for aggressive ATLL, showed promising results with response rate (RR) of 81% and MST of 13 months (Br J Haematol113:375,2001). To test the superiority of this VCAP-AMP-VECP regimen over biweekly-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone), we conducted a phase III trial. Methods: Previously untreated patients (pts) with aggressive ATLL, acute-, lymphoma- or unfavorable chronic-type, were randomized either to receive 6 courses of VCAP-AMP-VECP every 4 weeks (arm A) or 8 courses of biweekly-CHOP (arm B) with minimization method balancing performance status and institution. Both regimens were supported with G-CSF and intrathecal prophylaxis using cytarabine, methotrexate and prednisolone. Eligibility included preserved organ functions and aged 15–69 years. Primary endpoint was OS to be compared by log-rank test. Assuming 60 eligible pts in each arm, the study had 0.8 power to detect a 15% difference in 3-year OS at 0.05 one-sided alpha. Results: 118 pts (57 in arm A, 61 in arm B) were randomized between 07/98 and 10/03. Median follow-up time in all randomized pts was 11.0 months at 12/04. 72 % of the pts responded, with 23 pts achieving CR (40%) and 18 achieving partial response (PR; 32%) in arm A. The RR was 66%, with 15 pts achieving CR (25%) and 25 achieving PR (41%) in arm B. The median progression-free survival (PFS) time and PFS at one-year in arm A were 7.0 months and 28.1%, respectively, whereas 5.4 months and 16.2% in arm B. The MST and OS at 3 years in arm A were 12.7 months and 23.6%, respectively, whereas 10.9 months and 12.7% in arm B. Log-rank p-value for primary end point, OS, was 0.085. After adjustment of patients’ characteristics at registration by Cox regression, the p value became 0.029 because of unbalanced prognostic factors such as bulky lesion. In arm A vs. arm B, %G4 neutropenia, %G4 thrombocytopenia and %G4 infection were 98% vs. 83%, 74% vs. 17% and 7% vs. 3%, respectively. Three toxic deaths were reported in arm A. Conclusions: These results demonstrate that VCAP-AMP-VECP yields longer OS time than biweekly-CHOP but with higher toxicity profiles that are acceptable, and suggest that the former regimen should be the standard therapy for aggressive ATLL.

Download Full-text

The prognostic value of polymorphisms in the insulin-like growth factor receptor (IGFR) pathway in patients with locally advanced pancreatic cancer (LAPC)

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.4500 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 4500-4500

Author(s):

R. T. Shroff ◽

M. M. Javle ◽

X. Dong ◽

V. S. Kumar ◽

S. Krishnan ◽

...

Keyword(s):

Pancreatic Cancer ◽

Induction Chemotherapy ◽

Prognostic Value ◽

Cox Regression ◽

Karnofsky Performance Status ◽

Performance Status ◽

Locally Advanced ◽

Advanced Pancreatic Cancer ◽

Rank Test ◽

Cox Regression Analysis

4500 Background: The IGFR pathway is activated in pancreatic cancer and may result in aggressive disease course. The study of single nucleotide polymorphisms (SNPs) involved in this pathway may provide prognostic information and predict response to IGFR directed agents. We investigated IGFR pathway SNPs in patients with LAPC. Methods: We evaluated 39 SNPs from 7 candidate genes in the IGFR pathway (IGF1R, IGF2R, IGF1, IGF2, IRS1, IRS2, IGFBP3) in 105 LAPC patients. DNA extraction from whole blood was performed using the Qiagen Flexigene DNA and Promega Maxwell 16 kits. Genotyping was performed using the Sequenom method. Overall survival was measured from date of diagnosis to date of death or last follow-up. Kaplan-Meier plot, log-rank test, and Cox regression were used to compare survival of patients according to genotype corrected for previously identified prognostic factors, including induction chemotherapy, CA 19–9, albumin, LDH, hemoglobin and Karnofsky performance status (KPS). Results: Median survival time (MST) was 15 months (95% CI 13.3–16.7). Induction chemotherapy, LDH, CA 19–9 level, hemoglobin, and KPS were not significantly associated with survival. Serum albumin and three SNPs of the IGF pathway (IGF1R IVS20–3431A>G, IRS1 G971R, and IGF2 *4352A>G) were significantly associated with prognosis ( Table ). Two of the three genotypes remained as significant predictors for survival in Cox regression analysis when adjusted for clinical factors. A significant combined genotype effect was observed wherein patients with all three deleterious alleles had significantly worse survival than those with only two or one (10 vs. 16.3 vs. 21.3 months, p< 0.0001). Conclusions: These data suggest that SNPs in the IGFR pathway genes may have prognostic value for LAPC patients. This information may identify population subgroups that could benefit from IGFR-targeted agents. [Table: see text] No significant financial relationships to disclose.

Download Full-text

Radiosurgery and fractionated stereotactic body radiotherapy for patients with lung oligometastases

10.21203/rs.2.12297/v2 ◽

2019 ◽

Author(s):

Goda Kalinauskaite ◽

Ingeborg Tinhofer ◽

Marcus Kufeld ◽

Anne Kathrin Kluge ◽

Arne Grün ◽

...

Keyword(s):

Stereotactic Body Radiotherapy ◽

Cox Regression ◽

Lung Metastases ◽

Karnofsky Performance Status ◽

Performance Status ◽

Univariate Analysis ◽

Progression Free Survival ◽

Late Toxicity ◽

Invasive Treatment ◽

Free Survival

Abstract Background: Patients with oligometastatic disease can potentially be cured by using an ablative therapy for all active lesions. Stereotactic body radiotherapy (SBRT) is a non-invasive treatment option that lately proved to be as effective and safe as surgery in treating lung metastases (LM). However, it is not clear which patients benefit most and what are the most suitable fractionation regimes. The aim of this study was to analyze treatment outcomes after single fraction radiosurgery (SFRS) and fractionated SBRT (fSBRT) in patients with lung oligometastases and identify prognostic clinical features for better survival outcomes. Methods: Fifty-two patients with 94 LM treated with SFRS or fSBRT between 2010 and 2016 were analyzed. The characteristics of primary tumor, LM, treatment, toxicity profiles and outcomes were assessed. Kaplan-Meier and Cox regression analyses were used for estimation of local control (LC), overall survival (OS), progression free survival and distant metastases free survival (DMFS). Results: Ninety-four LM in 52 patients were treated using SFRS/fSBRT with a median of 2 lesions per patient (range: 1–5). The median planning target volume (PTV)-encompassing dose for SFRS was 24 Gy (range: 17-26) compared to 45 Gy (range: 20-60) in 2-12 fractions in fSBRT. The median follow-up time was 21 months (range: 3-68). LC rates at 1 and 2 years for SFSR vs. fSBRT were 89% and 83% vs. 75% and 59%, respectively (p=0.026). LM treated with SFSR were significantly smaller (p=0.001). The 1 and 2-year OS rates for all patients were 84% and 71%, respectively. In univariate analysis treatment with SFRS, an interval of ≥ 12 months between diagnosis of LM and treatment, non-colorectal cancer histology and BED <100 Gy were significantly associated with better LC. However, none of these parameters remained significant in the multivariate Cox regression model. OS was significantly better in patients with negative lymph nodes (N0), Karnofsky performance status (KPS) >70% and time to first metastasis ≥12 months. There was no grade 3 acute or late toxicity. Conclusions: We observed good LC and low toxicity rates after SFRS for small lung metastases. Longer time to first metastasis, good KPS and N0 predicted better OS.

Download Full-text

Optimizing the Treatment Mode for de Novo Metastatic Nasopharyngeal Carcinoma with Bone-Only Metastasis

10.21203/rs.3.rs-685930/v1 ◽

2021 ◽

Author(s):

Cheng Lin ◽

Sheng Lin ◽

li Li Zhu ◽

jun Shao Lin ◽

ji Jian Pan ◽

...

Keyword(s):

Bone Metastasis ◽

Nasopharyngeal Carcinoma ◽

Cox Regression ◽

De Novo ◽

Multivariable Analysis ◽

Progression Free Survival ◽

Rank Test ◽

Bone Lesions ◽

Metastatic Lesions ◽

Metastatic Nasopharyngeal Carcinoma

Abstract Purpose: No standard radiotherapy regimens was established in the treatment of de novo metastatic nasopharyngeal carcinoma (mNPC) with bone-only metastasis. The current study aimed to investigate the efficacy of palliative chemotherapy (PCT) plus locoregional radiotherapy (LLRT) with or without local radiotherapy (RT) to bone metastatic lesions in mNPC, and identify the optimal candidates.Methods: We retrospectively analyzed 141 de novo mNPC patients with bone-only metastasis who received at least two cycles of PCT with or without LLRT and RT to bone metastasis. The difference in survival was evaluated by the log-rank test. Univariable and multivariable analysis was made by Cox regression. Results: Patients who received PCT plus LLRT had significantly longer overall survival (OS) (45.0 months vs 13.5 months, HR = 0.30 , p = 0.001) and progression-free survival (PFS) (29.0 months vs 11.0 months, HR = 0.34, p = 0.014), especially in patients who had less than 3 metastatic bone lesions. Multivariate analysis confirmed that LRRT, more chemotherapy cycles (≥ 4) and limited number of bone metastasis (≤ 3) were favorable prognostic factors for OS. Subgroup analysis revealed that RT to metastatic bones had a tendency to prolong the survival time in the unselected population who received PCT plus LLRT (p > 0.05), while further data suggested that RT to metastatic bones dramatically improve OS (72.0 months vs 26.0 months, p = 0.002) and PFS (60.0 months vs 20.0 months, p = 0.006) for mNPC with less than 3 metastatic bone lesions.Conclusions: LLRT and RT to bone metastatic lesions followed by PCT in de novo mNPC with bone-only metastasis significantly prolonged survival in patients with less than 3 metastatic bone lesions.

Download Full-text

Association between prayer activity, inflammation, and survival in advanced cancer patients (ACPs): A preliminary study.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e19602 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e19602-e19602

Author(s):

Carlos Eduardo Paiva ◽

Bianca Sakamoto Ribeiro Paiva ◽

Camila Souza Crovador ◽

Sriram Yennurajalingam ◽

David Hui

Keyword(s):

Cox Regression ◽

Karnofsky Performance Status ◽

Performance Status ◽

Rank Test ◽

Advanced Cancer Patients ◽

Cancer Treatments ◽

Cross Sectional ◽

Reactive Protein ◽

Treatment Type ◽

Spearman Test

e19602 Background: Prayers represent an important coping strategy among ACPs. The Religion Practice Questionnaire (RPQ) is a self-reported measure of religiosity validated in the Brazilian population, and includes a question assessing prayer activity. In this cross sectional prospective study, we determined the association among prayer activity, inflammation and survival in ACPs. Methods: Consecutive ACPs presenting for initial consultation at our Palliative Care Outpatient Clinic between March and December 2011 were enrolled. RPQ was administered by a research nurse, and consists of 15 items rated on a 5-point Likertscale (0=none, 5=very much). High prayer score (HPS) was defined as >3/5 for question 11 ("I make personal prayers – spontaneous communications with God"). Inflammatory markers included white blood cell (WBC), albumin and C-reactive protein (CRP). Correlation analysis was performed using Spearman test. Survival was calculated from study enrolment until death, and analyzed with log rank test and Cox regression model including age, sex, KPS, treatment type and HPS. Results: 112 patients were enrolled: average age 59 y (range 21-85), female 53% (N=59), Karnofsky performance status (KPS) ≤70 46% (N=51), most common cancers breast and upper GI (N=41, 37%), no longer on active cancer treatments 48% (N=54). All patients were Christians, and 77 (69%) had HPS. RPQ was not associated with WBC, albumin, CRP nor survival. HPS correlated with WBC (r=-0.24, p=0.02), and CRP (r=-0.26, p=0.01) but not albumin (r=0.18, p=0.08). Patients with HPS survived longer (median 198 d vs. 121 d, p=0.040), which remained significant in multivariate analysis (Table). Conclusions: The act of praying was associated with decreased inflammation and improved survival in ACPs. Further studies are necessary to confirm these findings. [Table: see text]

Download Full-text

Treatment Results and Prognostic Factors of Brain Metastases From Ovarian Cancer: A Single Institutional Experience of 56 Patients

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000001341 ◽

2018 ◽

Vol 28 (8) ◽

pp. 1631-1638 ◽

Cited By ~ 6

Author(s):

Ji-Woong Kwon ◽

Joon Ho Yoon ◽

Myong Cheol Lim ◽

Jungnam Joo ◽

Heon Yoo ◽

...

Keyword(s):

Ovarian Cancer ◽

Prognostic Factors ◽

Brain Metastases ◽

Initial Treatment ◽

Karnofsky Performance Status ◽

Systemic Disease ◽

Performance Status ◽

Multivariable Analysis ◽

Progression Free Survival ◽

Free Survival

ObjectivesThe most appropriate treatments for brain metastases from ovarian cancer have not been established mainly because of its rarity. The objective of this study was to describe clinical results of treatment and prognostic factors of patients with brain metastases from ovarian cancer treated at a single institution.Materials and MethodsWe retrieved information from the electronic medical records of 56 consecutive patients (2.8%) with brain metastases, from a total of 2008 patients with ovarian cancer. Endpoints were the pattern of treatment failure, progression-free survival, and overall survival (OS).ResultsRadiation was the most common initial treatment for brain metastases (59%), followed by surgery (23%). The median progression-free survival was 9.8 months. Radiological progression was confirmed in 20 patients: 7 had leptomeningeal carcinomatosis (37%), 8 had local recurrence, and 5 had distant recurrence. Median OS was 11.25 months, and the 1-year OS rate was 48.2%. Patients received surgery for single metastasis as initial treatment showed median OS of 24.1 months, which was significantly prolonged compared with the other patients (P = 0.0002). Of the 48 patients who died, 29 (60%) died of systemic disease and 7 (15%) died of central nervous system progression. Karnofsky Performance Status greater than or equal to 70, control of systemic cancer, serous histology, and surgery for brain metastases were associated with improved OS in multivariable analysis (P < 0.05).ConclusionsSurgical resection for single or symptomatic brain metastases from ovarian cancer prolonged OS significantly. Multimodality treatment, including control of systemic cancer, appeared to be an important factor in prolonging OS.

Download Full-text

Quantitative volumetric assessment of baseline enhancing tumor volume as an imaging biomarker predicts overall survival in patients with glioblastoma

Acta Radiologica ◽

10.1177/0284185120953796 ◽

2020 ◽

pp. 028418512095379

Author(s):

Timo A Auer ◽

Marta Della Seta ◽

Federico Collettini ◽

Julius Chapiro ◽

Sebastian Zschaeck ◽

...

Keyword(s):

Overall Survival ◽

Dna Methyltransferase ◽

Tumor Volume ◽

Cox Regression ◽

Karnofsky Performance Status ◽

Performance Status ◽

Multivariable Analysis ◽

Imaging Biomarker ◽

Entire Cohort ◽

Volumetric Assessment

Background Glioblastoma multiforme (GBM) is the commonest malignant primary brain tumor and still has one of the worst prognoses among cancers in general. There is a need for non-invasive methods to predict individual prognosis in patients with GBM. Purpose To evaluate quantitative volumetric tissue assessment of enhancing tumor volume on cranial magnetic resonance imaging (MRI) as an imaging biomarker for predicting overall survival (OS) in patients with GBM. Material and Methods MRI scans of 49 patients with histopathologically confirmed GBM were analyzed retrospectively. Baseline contrast-enhanced (CE) MRI sequences were transferred to a segmentation-based three-dimensional quantification tool, and the enhancing tumor component was analyzed. Based on a cut-off percentage of the enhancing tumor volume (PoETV) of >84.78%, samples were dichotomized, and the OS and intracranial progression-free survival (PFS) were evaluated. Univariable and multivariable analyses, including variables such as sex, Karnofsky Performance Status score, O6-methylguanine-DNA-methyltransferase status, age, and resection status, were performed using the Cox regression model. Results The median OS and PFS were 16.9 and 7 months in the entire cohort, respectively. Patients with a CE tumor volume of >84.78% showed a significantly shortened OS (12.9 months) compared to those with a CE tumor volume of ≤84.78% (17.7 months) (hazard ratio [HR] 2.72; 95% confidence interval [CI] 1.22–6.03; P = 0.01). Multivariable analysis confirmed that PoETV had a significant prognostic role (HR 2.47; 95% CI 1.08–5.65; P = 0.03). Conclusion We observed a correlation between PoETV and OS. This imaging biomarker may help predict the OS of patients with GBM.

Download Full-text

Radiosurgery and fractionated stereotactic body radiotherapy for patients with lung oligometastases

10.21203/rs.2.12297/v3 ◽

2020 ◽

Author(s):

Goda Kalinauskaite ◽

Ingeborg Tinhofer ◽

Marcus Kufeld ◽

Anne Kathrin Kluge ◽

Arne Grün ◽

...

Keyword(s):

Stereotactic Body Radiotherapy ◽

Cox Regression ◽

Lung Metastases ◽

Karnofsky Performance Status ◽

Performance Status ◽

Univariate Analysis ◽

Progression Free Survival ◽

Late Toxicity ◽

Invasive Treatment ◽

Free Survival

Abstract Background: Patients with oligometastatic disease can potentially be cured by using an ablative therapy for all active lesions. Stereotactic body radiotherapy (SBRT) is a non-invasive treatment option that lately proved to be as effective and safe as surgery in treating lung metastases (LM). However, it is not clear which patients benefit most and what are the most suitable fractionation regimes. The aim of this study was to analyze treatment outcomes after single fraction radiosurgery (SFRS) and fractionated SBRT (fSBRT) in patients with lung oligometastases and identify prognostic clinical features for better survival outcomes. Methods: Fifty-two patients with 94 LM treated with SFRS or fSBRT between 2010 and 2016 were analyzed. The characteristics of primary tumor, LM, treatment, toxicity profiles and outcomes were assessed. Kaplan-Meier and Cox regression analyses were used for estimation of local control (LC), overall survival (OS), progression-free survival and distant metastases-free survival (DMFS). Results: Ninety-four LM in 52 patients were treated using SFRS/fSBRT with a median of 2 lesions per patient (range: 1–5). The median planning target volume (PTV)-encompassing dose for SFRS was 24 Gy (range: 17-26) compared to 45 Gy (range: 20-60) in 2-12 fractions in fSBRT. The median follow-up time was 21 months (range: 3-68). LC rates at 1 and 2 years for SFSR vs. fSBRT were 89% and 83% vs. 75% and 59%, respectively (p=0.026). LM treated with SFSR were significantly smaller (p=0.001). The 1 and 2-year OS rates for all patients were 84% and 71%, respectively. In univariate analysis treatment with SFRS, an interval of ≥ 12 months between diagnosis of LM and treatment, non-colorectal cancer histology and BED <100 Gy were significantly associated with better LC. However, none of these parameters remained significant in the multivariate Cox regression model. OS was significantly better in patients with negative lymph nodes (N0), Karnofsky performance status (KPS) >70% and time to first metastasis ≥12 months. There was no grade 3 acute or late toxicity. Conclusions: Longer time to first metastasis, good KPS and N0 predicted better OS. Good LC and low toxicity rates were achieved after short SBRT schedules.

Download Full-text

Radiosurgery and fractionated stereotactic body radiotherapy for patients with lung oligometastases

10.21203/rs.2.12297/v4 ◽

2020 ◽

Author(s):

Goda Kalinauskaite ◽

Ingeborg Tinhofer ◽

Marcus Kufeld ◽

Anne Kathrin Kluge ◽

Arne Grün ◽

...

Keyword(s):

Stereotactic Body Radiotherapy ◽

Cox Regression ◽

Lung Metastases ◽

Karnofsky Performance Status ◽

Performance Status ◽

Univariate Analysis ◽

Progression Free Survival ◽

Late Toxicity ◽

Target Volume ◽

Invasive Treatment

Abstract Background: Patients with oligometastatic disease can potentially be cured by using an ablative therapy for all active lesions. Stereotactic body radiotherapy (SBRT) is a non-invasive treatment option that lately proved to be as effective and safe as surgery in treating lung metastases (LM). However, it is not clear which patients benefit most and what are the most suitable fractionation regimens. The aim of this study was to analyze treatment outcomes after single fraction radiosurgery (SFRS) and fractionated SBRT (fSBRT) in patients with lung oligometastases and identify prognostic clinical features for better survival outcomes. Methods: Fifty-two patients with 94 LM treated with SFRS or fSBRT between 2010 and 2016 were analyzed. The characteristics of primary tumor, LM, treatment, toxicity profiles and outcomes were assessed. Kaplan-Meier and Cox regression analyses were used for estimation of local control (LC), overall survival (OS) and progression-free survival.Results: Ninety-four LM in 52 patients were treated using SFRS/fSBRT with a median of 2 lesions per patient (range: 1–5). The median planning target volume (PTV)-encompassing dose for SFRS was 24 Gy (range: 17-26) compared to 45 Gy (range: 20-60) in 2-12 fractions in fSBRT. The median follow-up time was 21 months (range: 3-68). LC rates at 1 and 2 years for SFSR vs. fSBRT were 89% and 83% vs. 75% and 59%, respectively (p=0.026). LM treated with SFSR were significantly smaller (p=0.001). The 1 and 2-year OS rates for all patients were 84% and 71%, respectively. In univariate analysis treatment with SFRS, an interval of ≥ 12 months between diagnosis of LM and treatment, non-colorectal cancer histology and BED <100 Gy were significantly associated with better LC. However, none of these parameters remained significant in the multivariate Cox regression model. OS was significantly better in patients with negative lymph nodes (N0), Karnofsky performance status (KPS) >70% and time to first metastasis ≥12 months. There was no grade 3 acute or late toxicity. Conclusions: Longer time to first metastasis, good KPS and N0 predicted better OS. Good LC and low toxicity rates were achieved after short SBRT schedules.

Download Full-text

Safety and efficacy of chemotherapy in older adults with locally advanced and metastatic pancreatic ductal adenocarcinoma (PDAC).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.654 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 654-654 ◽

Cited By ~ 1

Author(s):

Lorena Ostios-Garcia ◽

Patricia Saade ◽

Joseph Elan Grossman ◽

Leanne Lanniello ◽

Andrea J. Bullock

Keyword(s):

Older Adults ◽

Cox Regression ◽

Performance Status ◽

Locally Advanced ◽

Progression Free Survival ◽

Ductal Adenocarcinoma ◽

Rank Test ◽

Safety And Efficacy ◽

Exact Test ◽

Univariate Analyses

654 Background: PDAC is often diagnosed in patients (pts) ≥75yrs. However, older adults comprise a small proportion of subjects in prospective trials, and there is little reported on the safety and efficacy of chemotherapy in this population. Methods: Records were reviewed on all pts ≥75yrs treated with chemotherapy for locally advanced and metastatic PDAC at a single institution from April 2010 - March 2018. Response rate (RR), progression free survival (PFS), overall survival (OS) and toxicities were compared among the different regimens, and among pts < or ≥80yrs. Survival was estimated with the Kaplan-Meier method and compared by log-rank test. Univariate analyses were performed by Fisher’s exact test and multivariate analyses by a Cox-regression model to identify factors associated with PFS and OS in this population. Results: 67 pts were treated, median age 81yrs (range: 75-90), stage III (34, 51%) and IV (33, 49%). Chemotherapy regimens included: gemcitabine alone (39), gemcitabine/nab-paclitaxel (17), gemcitabine/vinorebine (1), FOLFOX (8) and FOLFIRINOX (2). 59 (88%) pts required dose adjustments due to toxicity; no differences by age or regimen. RR, PFS, and OS did not differ by age or regimen (Table), although sample size was small. Age >80yrs was associated with reduced PFS (p 0.03). On univariate analyses liver metastases and performance status (PS)>1 were associated with reduced OS; PS>1 was associated with reduced OS on multivariate analysis. Conclusions: Among pts with locally advanced and metastatic PDAC ≥75yrs, there were no differences in RR, PFS or OS by chemotherapy regimen. PS was the only variable associated with reduced OS. Older adults with PS 0-1 are likely to benefit from chemotherapy for non-resectable PDAC.[Table: see text]

Download Full-text