Impact of KRAS on outcomes of patients with unresectable colorectal liver metastases (CRLM).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 510-510
Author(s):  
Celina Ang ◽  
Alexandra N. Gewirtz ◽  
Joanne F. Chou ◽  
Marinela Capanu ◽  
Efsevia Vakiani ◽  
...  
Keyword(s):  
Overall Survival ◽  
Liver Resection ◽  
Systemic Chemotherapy ◽  
Univariate Analysis ◽  
Hepatic Arterial Infusion ◽  
Progression Free Survival ◽  
Rank Test ◽  
Related Factors ◽  
Hazards Model ◽  
The Impact

510 Background: In patients with resected CRLM, mutant (MUT) KRAS may confer a worse prognosis than wild-type (WT) KRAS (Karagkounis et al., ASCO 2012, abs 3616; Kemeny et al., ASCO 2013, abs 3609). We analyzed the impact of KRAS on the outcomes of patients with unresectable CRLM treated with hepatic arterial infusion (HAI) + systemic chemotherapy. Methods: Median overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan Meier methods. The log rank test was used to examine the association of patient demographics and disease-related factors including KRAS mutation status with OS and PFS. Cox proportion hazards model was used to examine the association of liver resection with survival outcomes by treating liver resection as a time dependent covariate. Results: Of 93 patients: 59 male, 34 female; 77 Caucasian, 16 non-Caucasian; 66 were age < 60 years, 27 were age > 60 years; 70 were KRAS WT and 23 were KRAS MUT; 59 had chemotherapy pre-HAI pump placement and 53 subsequently underwent liver resection. Median PFS and OS were 13.3 months and 45.7 months, respectively. Age, sex and race were not associated with PFS or OS. Univariate analysis of the impact of KRAS, pre-HAI chemotherapy, and subsequent liver resection on PFS and OS is presented in the Table. Multivariate analysis including important variables did not change outcome. Conclusions: In patients with unresectable CRLM treated with HAI and systemic chemotherapy, overall survival tended to be improved in KRAS WT vs MUT patients. [Table: see text]

Single nucleotide polymorphisms (SNPs) as predictors of efficacy of cabazitaxel in patients with metastatic castration-resistant prostate cancer (mCRPC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17582-e17582
Author(s):  
Daniel Herrero Rivera ◽  
Ignacio Duran ◽  
Laura Marcos Kovandzic ◽  
Javier Puente ◽  
Begona Mellado ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Gleason Score ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Rank Test ◽  
Genetic Constitution ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
The Impact

e17582 Background: Cabazitaxel is a semi-synthetic derivative of a natural taxoid approved for the treatment of mCRPC patients (pts) after failure to docetaxel. Despite its proven efficacy, there is variability in the response, progression-free survival (PFS) and overall survival (OS) of pts. Changes in the genetic constitution of the individual such as the SNPs could explain this variability. The aim of this study was to evaluate the impact of certain SNPs in cabazitaxel activity. Methods: Clinical data from 67 mCRPC pts treated with cabazitaxel between March 2011 and October 2016 were collected. DNA was isolated from formalin fixed paraffin-embedded tumor samples. 56 SNPs in 5 genes related with metabolism and/or mechanism of action of cabazitaxel (CYP3A4, CYP3A5, ABCB1, TUBB1, CYP2C8) were chosen based on their Minor Allele Frequency, linkage disequilibrium and information from dbSNP and analyzed by TaqMan OpenArray (Lifetech). The presence/absence of mutant alleles of the selected SNPs was correlated with clinical features, progression free survival (PFS) and overall survival (OS) of prostate cancer. Chi-square test and Kaplan-Meier with log-rank test were used for statistical analyses. Results: The median age was 61 years (range 44-82). 56.7% (n = 38) had a Gleason score ≥8 and 94% had received docetaxel in first line. Type of response to cabazitaxel was associated with median OS (Partial response = 24.35 months, Stable disease = 11.16 months, Progression disease = 5.8 months; p= 0.045). Univariate analysis, showed worsed OS at 1 year for wild type status of SNP rs151352 (OR = 4, 95%CI 1.27-12.58, p= 0.029). In addition, two SNPs (rs11773597, rs1202186) were associated with radiological response to cabazitaxel ( p= 0.031 and p= 0.030 respectively). Other 7 SNPs (rs11773597, rs2235040, rs1045642, rs1419745, rs1202170, rs6949448, rs11572093) were associated ( p<0.05) with Gleason score, pain, PSA doubling time, febrile neutropenia and asthenia. Conclusions: A particular SNP profile could be predictive of efficacy and related with toxicity in mCRPC population treated with cabazitaxel after progression to docetaxel. These outcomes become particularly relevant in patient selection given the recent results of the CARD trial.

Comparative study of six cycles versus twelve cycles of adjuvant temozolomide post concurrent chemoradiation in newly diagnosed glioblastoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e13034-e13034
Author(s):  
Menal Bhandari ◽  
Ajeet K Gandhi ◽  
Pramod Kumar Julka ◽  
Chitra Sarkar ◽  
Dayanand Sharma ◽  
...  
Keyword(s):  
Univariate Analysis ◽  
Progression Free Survival ◽  
Extent Of Resection ◽  
Rank Test ◽  
Karnofsky Performance Score ◽  
Free Survival ◽  
Kaplan Meier ◽  
The Impact ◽  
Mib 1

e13034 Background: This study assesses the impact of 6 cycles of adjuvant TMZ (conventional arm) versus 12 cycles (Extended arm) on Progression free survival (PFS), evaluate the toxicity and correlate the outcome with EGFR, P53 and MIB I labelling Index. Methods: Between December 2010 to October 2012, 36 post operative patients of Glioblastoma between age 18-65 years and Karnofsky Performance Score (KPS) ≥ 70 were included. Patients were randomized to receive Radiation with a dose of 60 Gray in 30 fractions over 6 weeks at 2 gray/fraction with concomitant TMZ (75 mg/m2/day) and Adjuvant therapy with either 6 or 12 cycles of TMZ(150 mg/m2 for 5 days, 28 days cycle). Patients were then assessed monthly clinically and imaged with MRI/CT every 3 monthly or when symptomatic. Toxicity was assessed using CTCAE version 3.0. Statistical Analysis was done using SPSS version 17.0.Kaplan Meier method was used for analysis of survival and log rank test was used for assessing the impact of variables on survival. Results: Of 36 patients, 18 patients were treated in each arm. Median age and KPS in both the arms was 47 years and 80 respectively. 44 % patients in the conventional arm and 50% patients in the Extended arm underwent complete surgical resection. 22% patients in the conventional arm and 28% in the extended arm did not complete their intended treatment. Grade ¾ Thrombocytopenia was seen in 16% in the extended arm and 0% in the conventional arm.EGFR, P 53 and MIB 1 >20% was seen in 26%, 45% and 20% patients respectively, overall. Median follow up was 18 months for both the arms (Range 10-23 months).At last follow up,8 patients in each arm had progression. Median PFS was 10 months vs.18.4 months (p 0.47) in conventional and extended arm respectively. On Univariate analysis, patients with KPS ≤ 80 had poorer survival than those >80 (Median PFS 9.5 Months vs. 16.9 Months; p 0.02).Age, extent of resection, EGFR, P53, MIB 1 did not significantly alter survival in the two treatment groups. Conclusions: Our study showed that schedule of extended Temozolomide is well tolerated by patients and tend to have better progression free survival. Further prospective randomized studies are needed to validate the findings of our study.

Delays from neoadjuvant chemotherapy to interval debulking surgery and survival in ovarian cancer

2020 ◽  
Vol 30 (10) ◽  
pp. 1554-1561
Author(s):  
Ying L Liu ◽  
Qin C Zhou ◽  
Alexia Iasonos ◽  
Olga T Filippova ◽  
Dennis S Chi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Neoadjuvant Chemotherapy ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Debulking Surgery ◽  
Free Survival ◽  
Interval Debulking Surgery ◽  
The Impact

IntroductionDelays from primary surgery to chemotherapy are associated with worse survival in ovarian cancer, however the impact of delays from neoadjuvant chemotherapy to interval debulking surgery is unknown. We sought to evaluate the association of delays from neoadjuvant chemotherapy to interval debulking with survival.MethodsPatients with a diagnosis of stage III/IV ovarian cancer receiving neoadjuvant chemotherapy from July 2015 to December 2017 were included in our analysis. Delays from neoadjuvant chemotherapy to interval debulking were defined as time from last preoperative carboplatin to interval debulking >6 weeks. Fisher’s exact/Wilcoxon rank sum tests were used to compare clinical characteristics. The Kaplan–Meier method, log-rank test, and multivariate Cox Proportional-Hazards models were used to estimate progression-free and overall survival and examine differences by delay groups, adjusting for covariates.ResultsOf the 224 women, 159 (71%) underwent interval debulking and 34 (21%) of these experienced delays from neoadjuvant chemotherapy to interval debulking. These women were older (median 68 vs 65 years, P=0.05) and received more preoperative chemotherapy cycles (median 6 vs 4, P=0.003). Delays from neoadjuvant chemotherapy to interval debulking were associated with worse overall survival (HR 2.4 95% CI 1.2 to 4.8, P=0.01), however survival was not significantly shortened after adjusting for age, stage, and complete gross resection, HR 1.66 95% CI 0.8 to 3.4, P=0.17. Delays from neoadjuvant chemotherapy to interval debulking were not associated with worse progression-free survival (HR 1.55 95% CI 0.97 to 2.5, P=0.062). Increase in number of preoperative cycles (P=0.005) and lack of complete gross resection (P<0.001) were the only variables predictive of worse progression-free survival.DiscussionDelays from neoadjuvant chemotherapy to interval debulking were not associated with worse overall survival after adjustment for age, stage, and complete gross resection.

scholarly journals A new prognostic score for predicting survival in patients treated with robotic stereotactic radiotherapy for brain metastases

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Magdalena Stankiewicz ◽  
Bartlomiej Tomasik ◽  
Slawomir Blamek
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Brain Metastases ◽  
Bootstrap Method ◽  
Prognostic Score ◽  
Univariate Analysis ◽  
Prognostic Index ◽  
Rank Test ◽  
Robotic Radiosurgery ◽  
The Impact

AbstractThe study aimed to analyze potential prognostic factors in patients treated with robotic radiosurgery for brain metastases irrespective of primary tumor location and create a simple prognostic score that can be used without a full diagnostic workup. A retrospective analysis of 142 patients with 1–9 brain metastases treated with stereotactic radiosurgery (1–4 fractions) was performed. Volumes of all lesions were calculated using linear dimensions of the tumors (CC, LR, AP) and 4/3*π*(CC/2)*(LR/2)*(AP/2) formula. Kaplan–Meier method and log-rank test were used to analyze survival. Variables significantly associated with overall survival in univariate analysis were included in Cox multivariate analysis. The validity of the model was tested with the bootstrap method. Variables from the final model were used to construct a new prognostic index by assigning points according to the impact of a specific variable on overall survival. In the multivariate analysis, four factors: Karnofsky Performance Status (p = 0.000068), number of brain metastases (p = 0.019), volume of the largest lesion (p = 0.0037), and presence of extracerebral metastases (p = 0.0017), were independent predictors of survival. Total scores ranged from 0 to 12 points, and patients were divided into four groups based on median survival of each subgroup: 0–1 points—18.8 months, 2–3 points—16.9 months, 4–5 points—5.6 months, and ≥ 6 points—4.9 months (p < 0.001). The new prognostic index is simple to calculate. It has a strong prognostic value in a heterogeneous population of patients with a various number of brain metastases, but its value requires confirmation in another cohort.

Platelet microparticles (PMP): A predictive factor of overall survival in hormone-refractory prostate cancer (HRPC) patients treated by chemotherapy

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4639-4639
Author(s):  
A. Banu ◽  
D. Helley ◽  
E. Banu ◽  
A. M. Fischer ◽  
F. Scotte ◽  
...  
Keyword(s):  
Overall Survival ◽  
Growth Factor ◽  
Predictive Factor ◽  
Cancer Metastasis ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Specific Antigen ◽  
Rank Test ◽  
Interaction Term ◽  
The Impact

4639 Background: Several studies suggest a causal relationship between platelets activation and cancer metastasis. Activated platelets release PMP, VEGF (vascular endothelial growth factor) and bFGF (basic fibroblast growth factor) which could play a role in patient outcome. Methods: Eligible chemonaive HRPC patients (pts) were required to have: ECOG performance status (PS) ≤2, progressive disease after antiandrogen withdrawal. Before chemotherapy, we quantified PMP in whole blood by flow cytometry using an anti-CD41 monoclonal antibody and plasmatic VEGF and bFGF by ELISA. As primary endpoint, we prospectively evaluated the impact of PMP on overall survival (OS) by Cox regression and log-rank test. Secondary, we studied the correlation between PMP and platelets, and their relationship with OS, incorporating an interaction term in the modelling (PMP and platelets). Results: Between July 2001 and April 2004, thirty-eight HRPC pts were treated by chemotherapy [docetaxel (92%), mitoxantrone (8%)] in our center. Median age was 69 years, with median values of hemoglobin 125 g/L, baseline prostate-specific antigen (PSA) 37.7 ng/mL, PMP 6 867 per μL, VEGF 18.1 pg/mL and bFGF 2.8 pg/mL. Significant correlations were observed between PMP and ECOG PS, hormone-sensitivity duration, Gleason and platelets. Median OS was significantly lower in pts with high PMP values (>6 788 per μL), compared to low PMP pts: 16.7 months (95% CI, 5.1–28.2) vs 25.2 months (95% CI, 20.2–30.3), P = 0.025, log-rank. Univariate analysis by Cox regression showed a significant relationship between OS and PMP level [HR = 0.41 (95% CI, 0.19–0.92), P = 0.04]. PMP kept their significance after adjusting by multivariate analysis for baseline hemoglobin, number of metastatic sites, and PSA doubling-time [HR = 0.37 (95% CI, 0.16–0.87), P = 0.02)]. An interaction term (PMP and platelets) was also predictive on OS (P = 0.01). Conclusions: PMP and their interaction with platelets were a predictive factor of OS in HRPC pts. Our analysis showed that the dynamic interaction between PMP and platelets has a major impact on outcome of HRPC pts. No significant financial relationships to disclose.

High-Risk Cytogenetics Multiple Myeloma: Impact of Consolidation and Maintenance

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2271-2271 ◽  
Author(s):  
Victor Jimenez-Zepeda ◽  
Peter Duggan ◽  
Paola Neri ◽  
Jason Tay ◽  
Fariborz Rashid-Kolvear ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Clinical Outcomes ◽  
Research Funding ◽  
Progression Free Survival ◽  
Categorical Variables ◽  
Rank Test ◽  
Fisher Exact Test ◽  
Free Survival ◽  
The Impact

Abstract Introduction MM is a very heterogeneous disease for which several new treatments have become available over the past decade. With the advent of novel agents, the outcomes of this disease have improved dramatically. Unfortunately, High-risk myeloma (HRM) defined by the presence of del(17p), t(4;14), t(14;16), del13q by conventional karyotype and hypodiploidy, continues to exhibit poorer outcomes. Based on the above mentioned, we aimed to assess the clinical outcomes of patients with HRM treated at our center. Methods All consecutive HRM patients who underwent single auto-SCT at Tom Baker Cancer Center (TBCC) from 01/2004 to March/2016 were evaluated. HRM was defined by FISH and conventional karyotype when available. Two-sided Fisher exact test was used to test for differences between categorical variables. A p value of <0.05 was considered significant. Survival curves were constructed according to the Kaplan-Meier method and compared using the log rank test. All statistical analyses were performed by using the SPSS 22.0 software. Results 73 consecutive patients with HRM underwent single auto-SCT at our Institution over the defined period. Clinical characteristics are shown in Table 1. Eighty-seven percent of patient received bortezomib-containing regimens as induction regimens. Day-100 response post-ASCT is seen in Table 1. Consolidation was given to 41.7% and maintenance to 79% of cases. At the time of analysis, 43 patients are still alive and 40 have already progressed. Median OS and PFS were 50.8 and 21.9 months, respectively for the whole group. Median OS was 50.4 months for the group receiving consolidation compared to 39 months for those without (p=0.1). In addition, median PFS was longer in the group treated with consolidation (NR, Estimate 25 months vs 13.5 months, p=0.02, Fig1a). Furthermore, OS and PFS were longer in the group receiving some form of maintenance compared to those without (56.3 and 22.5months vs 19.9 and 9 months, p=0.04 and 0.01, respectively) (Fig 1b and c). In conclusion, HRM is an aggressive form of myeloma where the OS and PFS are shorter than the standard risk MM. Consolidation and maintenance strategies seemed to increase both OS and PFS in our current report, but clinical outcomes are still poor. Novel strategies such as immune modulation,check-point inhibition, among others are needed to maximize the impact of the consolidation and maintenance phases in this group of patients. Progression-Free Survival and consolidation Progression-Free Survival and consolidation Figure 1 Overall survival and maintenance Figure 1. Overall survival and maintenance Figure 2 Progression-Free survival and maintenance Figure 2. Progression-Free survival and maintenance Disclosures Jimenez-Zepeda: Janssen: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Celgene, Janssen, Amgen, Onyx: Honoraria. Neri:Celgene and Jannsen: Consultancy, Honoraria. Bahlis:Amgen: Consultancy, Honoraria; BMS: Honoraria; Onyx: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Other: Travel Expenses, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Other: Travel Expenses, Research Funding, Speakers Bureau.

scholarly journals Protocol for a phase III randomized trial of chemoradiation and systemic chemotherapy vs. systemic chemotherapy alone in patients with unresectable nonmetastatic cholangiocarcinoma

2017 ◽  
Vol 4 (1) ◽  
pp. 14
Author(s):  
Supriya Chopra ◽  
Reena Engineer ◽  
Ashwathy Susan Mathew ◽  
Shaesta Mehta ◽  
Vikas Ostwal ◽  
...  
Keyword(s):  
Overall Survival ◽  
Systemic Chemotherapy ◽  
Performance Status ◽  
Randomized Study ◽  
Progression Free Survival ◽  
Late Toxicity ◽  
Phase Iii ◽  
Current Standard ◽  
The Impact ◽  
Doublet Chemotherapy

<p class="abstract"><strong>Background:</strong> Systemic doublet chemotherapy constitutes the current standard of care for patients with unresectable non-metastatic cholangiocarcinoma. The use of doublet chemotherapy is associated with median survival of 11.7 months. Concurrent chemo-radiation in this cohort is associated with similar overall survival however the impact of combination of chemoradiation and systemic chemotherapy on overall survival has not been investigated.  The present phase III randomized study investigates the impact of chemoradiation in addition to systemic chemotherapy on overall survival.</p><p class="abstract"><strong>Methods:</strong> Patients older than 18 years of age with diagnosis of unresectable non-metastatic cholangiocarcinoma with performance status 0-2and preserved liver function (Child Pugh score up to B7) will be eligible for study participation. The trial is designed such that patients will undergo stratified randomization (extra-hepatic vs. intrahepatic) either into systemic chemotherapy (standard arm) or chemo-radiation and systemic chemotherapy arm (experimental arm). The primary aim of the study is to compare difference in overall survival. The secondary aims of the study will focus on loco regional progression free survival and cause specific survival. The study will also report on the acute and late toxicity, quality of life and resectability rates in both the study arms. To demonstrate 7-month improvement in overall survival from 11 to 18 months a sample size of 142 is needed. Accounting for attrition a total of 155 patients will be accrued. All study subjects will be accrued after written informed consent. The trial is approved by the institutional ethics review board.</p><p>This trial is registered with ClinicalTrials.gov as NCT02773485</p>

scholarly journals Multimodal Treatment in Metastatic Colorectal Cancer (mCRC) Improves Outcomes—The University College London Hospital (UCLH) Experience

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3545
Author(s):  
Nalinie Joharatnam-Hogan ◽  
William Wilson ◽  
Kai Keen Shiu ◽  
Giuseppe Kito Fusai ◽  
Brian Davidson ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Multimodal Treatment ◽  
Systemic Chemotherapy ◽  
Multimodal Therapy ◽  
Primary Tumour ◽  
Univariate Analysis ◽  
Survival Outcomes ◽  
The Impact

Background: Despite notable advances in the management of metastatic colorectal cancer (mCRC) over the last two decades, treatment intent in the vast majority of patients remains palliative due to technically unresectable disease, extensive disease, or co-morbidities precluding major surgery. Up to 30% of individuals with mCRC are considered potentially suitable for primary or metastasis-directed multimodal therapy, including surgical resection, ablative techniques, or stereotactic radiotherapy (RT), with the aim of improving survival outcomes. We reviewed the potential benefits of multimodal therapy on the survival of patients with mCRC treated at the UCLH. Methods: Clinical data on baseline characteristics, multimodal treatments, and survival outcomes were retrospectively collected from all patients with mCRC receiving systemic chemotherapy between January 2013 and April 2017. Primary outcome was the impact of multimodal therapy on overall survival, compared to systemic therapy alone, and the effect of different types of multimodal therapy on survival outcome, and was assessed using the Kaplan–Meier approach. All analyses were adjusted for age, gender, and side of primary tumour. Results: One-hundred and twenty-five patients with mCRC were treated during the study period (median age: 62 years (range 19–89). The liver was the most frequent metastatic site (78%; 97/125). A total of 52% (65/125) had ≥2 lines of systemic chemotherapy. Of the 125 patients having systemic chemotherapy, 74 (59%) underwent multimodal treatment to the primary tumour or metastasis. Median overall survival (OS) was 25.7 months [95% Confidence Interval (CI) 21.5–29.0], and 3-year survival, 26%. Univariate analysis demonstrated that patients who had additional procedures (surgery/ablation/RT) were significantly less likely to die (Hazard Ratio (HR) 0.18, 95% CI 0.12–0.29, p < 0.0001) compared to those receiving systemic chemotherapy alone. Increasing number of multimodal procedures was associated with an incremental increase in survival—with median OS 28.4 m, 35.7 m, and 64.8 m, respectively, for 1, 2, or ≥3 procedures (log-rank p < 0.0001). After exclusion of those who received systemic chemotherapy only (n = 51), metastatic resections were associated with improved survival (adjusted HR 0.36, 95% CI 0.20–0.63, p < 0.0001), confirmed in multivariate analysis. Multiple single-organ procedures did not improve survival. Conclusion: Multimodal therapy for metastatic bowel cancer is associated with significant survival benefit. Resection/radical RT of the primary and resection of metastatic disease should be considered to improve survival outcomes following multidisciplinary team (MDT) discussion and individual assessment of fitness.

Bortezomib-Containing Regimens (BCR) for the Treatment of Non-Transplant Eligible Multiple Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1846-1846
Author(s):  
Victor H Jimenez-Zepeda ◽  
Peter Duggan ◽  
Paola Neri ◽  
Nizar J Bahlis
Keyword(s):  
Overall Survival ◽  
Research Funding ◽  
Clinical Characteristics ◽  
Progression Free Survival ◽  
Categorical Variables ◽  
Rank Test ◽  
Cancer Center ◽  
Fisher Exact Test ◽  
Free Survival ◽  
The Impact

Abstract Introduction In patients not eligible for transplant due to age and/or co-morbidities, the selection of up-front therapy needs to balance efficacy and toxicity. Recently, regimens with bortezomib, a proteasome inhibitor proven to be efficacious in myeloma, have been reported. Based on these findings, we aimed to evaluate the impact of different bortezomib combinations for the treatment of non transplant-eligible MM. Methods All- consecutive patients treated with bortezomib-containing regimens (BCR) at Tom Baker Cancer Center (TBCC) from 01/2006 to June/2015 were evaluated. Definitions of response and progression were used according to the EBMT modified criteria and a category of very good partial response (VGPR) was added. Two-sided Fisher exact test was used to test for differences between categorical variables. A p value of <0.05 was considered significant. Survival curves were constructed according to the Kaplan-Meier method and compared using the log rank test. Results 113 consecutive patients with MM received BCR. Thirty-three patients were treated with cyclophosphamide, bortezomib and dexamethasone (CyBorD), 41 with bortezomib, melphalan and prednisone (VMP) and 39 with bortezomib and dexamethasone (VD). Clinical characteristics are shown in Table 1. At the time of analysis, 20, 17 and 18 patients in the CyBorD, VMP and VD groups are still alive and 14, 33 and 30 have already progressed, respectively. ORR and VGPR rates were 93.9%/75.7%, 80%/53% and 76%/48% (p=0.001) for patients treated with CyBorD, VMP and VD, respectively. Median OS was NR for CyBorD, compared to 41months and 37 months for VMP and VD patients (p=0.6). Median PFS was 16.7 months for CyBorD compared to 17.5 months and 11 months for VMP and VD (P=0.6), respectively. The rate of treatment discontinuation and median number of cycles were: 9%, 26% and 12.8% and 6, 7.5 and 4 cycles for CyBorD, VMP and VD patients, respectively. Patients were to receive 6-9 cycles of treatment and the regimen could be continued to a maximum of 2 years at the discretion of the treating hematologist based on tolerability and response. Nine patients (27%) in the CyBorD group and 17 (41.4%) and 4 (10%) in the VMP and VD group received maintenance treatment. Median OS and PFS was longer for the group receiving maintenance (62 months vs 32 months and 23 months vs 10 months, p=0.007). In conclusion, bortezomib containing regimens are efficacious in the treatment of non-transplant eligible MM. Patients receiving maintenance appeared to exhibit longer PFS and OS. Very elderly patients should be subjected to frailty and comorbidity indexes aiming to decrease toxicity and prolong survival. Table 1. Clinical Characteristics Characteristic CyBorD, n=33 VMP, n=41 VD, n=39 Age (median) 58 58 58 GenderMaleFemale 20 (60.6%)13 (39.4%) 22 (53.6%)19 (46.4%) 26 (66.6%)13 (33.4%) Hb (g/L) 107 110 103 Calcium (µmol/L) 2.4 2.35 2.31 Creatinine (µmol/L) 115.5 103 108 B2microglobulin (µmol/L) 4.1 3.42 5.9 Albumin (g/L) 31 31 30 Stage IStage IIStage III 6 (12.1%)14 (42.4%)13 (45.5%) 9 (21.9%)19 (46.3%)13 (31.8%) 4 (10.2%)16 (41%)18 (48.8%) LDH (IU/L) 185 179 174 BMPC (%) 31 30 33.5 Heavy chain:IgGIgAFLC onlyIgDIgMBiclonal 2247000 19148000 21107010 Light chain:KappaLambdaBiclonal 16170 29120 24150 High riskStandard risk 5 (15%) 28 6 (14.6%)35 8 (20%)31 Ab: BMPC: Bone marrow plasma cells. Figure 1. Overall survival for patients receiving CyBorD, VMP and VD Figure 1. Overall survival for patients receiving CyBorD, VMP and VD Figure 2. Progression-Free survival for patients receiving CyBorD, VMP and VD Figure 2. Progression-Free survival for patients receiving CyBorD, VMP and VD Figure 3. OS for patients receiving CyBorD, VMP and VD maintenance Figure 3. OS for patients receiving CyBorD, VMP and VD maintenance Disclosures Jimenez-Zepeda: Celgene: Honoraria; Amgen: Honoraria; J&J: Honoraria. Duggan:Jansen: Honoraria; Celgene: Honoraria. Neri:Celgene: Research Funding. Bahlis:Johnson & Johnson: Speakers Bureau; Johnson & Johnson: Consultancy; Amgen: Consultancy; Johnson & Johnson: Research Funding; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau.

NTRK, ALK and RET rearrangements in salivary gland cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18023-e18023
Author(s):  
Svetlana Kutukova ◽  
Evgeny Imyanitov ◽  
Natalia P. Beliak ◽  
Julia V. Ivaskova ◽  
Alexandra Razumova
Keyword(s):  
Overall Survival ◽  
Salivary Gland ◽  
Poor Prognosis ◽  
Progression Free Survival ◽  
Rank Test ◽  
Salivary Gland Cancer ◽  
Prognosis Factor ◽  
Free Survival ◽  
Kaplan Meier ◽  
The Impact

e18023 Background: We investigated the prevalence of rare genes rearrangements in salivary gland adenocarcinomas and the impact of these fusions on overall survival (OS) and progression free survival (PFS). Methods: For 51/60 (85.0%) patients with different types salivary gland adenocarcinomas (stage I-IVA), sufficient tumor tissue was available for molecular characterization by polymerase chain reaction (PCR) and has been tested for NTRK, ALK, ROS1, RET and MET deletion. OS and PFS curves were estimated with the Kaplan-Meier method and compared using the log-rank test. Results: Two cases (3.92%) of NTRK translocation were found, both are a classic rearrangement of ETV6ex5; NTRK3ex15. Of the other alterations, 2 cases (3.92%) of unbalanced ALK expression. However, it was not possible to establish the option of rebuilding. In addition, were found 2 cases (3.92%) of highly balanced expression of NTRK2 and ALK, and one case (1.96%) of high expression of ROS1. RET mRNA expression was detected in 13 of 48 cases (27.08%). NTRK, RET, ALK and ROS1 fusions were equally common in both men and women (p = 0.89), not depending on age (0.76). All patients bearing ALK, RET and NTRK fusions had shorter overall survival - 13.2 months, 95% confidence interval [CI] 13.0 to 32.0 months in multivariable model 105.0 moth (95% CI 105.0-105.0) in patient's group without mutations (p = 0.1817); and shorter PFS: 5.0 month (95% CI 5.0-16.0) vs not reached PFC in group (mean of PFS 63.15±5.58; 95% CI 52.20-74.09) without mutations (p = 0.0467). ALK fusion is an independent poor prognosis factor affecting on OS: p = 0.0168, hazard ratio (HR) = 8.65 (95% CI 1.47-50.77); and poor prognosis factor affecting on PFS: p = 0.0170, HR = 7.13 (95% CI 1.42-35.80). Conclusions: ALK, NTRK, ROS1 and RET mutations define a new rare subtype of salivary gland adenocarcinomas with enormously poor prognosis. The presence ALK-mutation is an independent poor prognosis factorб negatively affecting both overall survival and progression-free survival. It’s advisable to consider the possibilities of using ALK, NTRK and RET inhibitors in this cohort of patients.

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