Anti-Her2neu directed therapy in advanced gall bladder cancer: A prospective, multicenter experience from India.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16682-e16682
Author(s):  
Chandan Krushna Das ◽  
Amol Patel ◽  
Abhishek Raj ◽  
Vineet Govinda Gupta ◽  
Prashant Mehta ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Free Survival ◽  
Northern India ◽  
Multicenter Prospective Observational Study ◽  
Next Generation Sequencing Ngs ◽  
Advanced Gall Bladder Cancer ◽  
Historical Controls ◽  
Generation Sequencing ◽  
Standard Techniques

e16682 Background: Prognosis of Gallbladder cancer (GBC) remains unchanged over the last 20 years. Her2neu amplification is present in 17% of cases of advanced GBC. We present our experience of anti Her2 targeted therapy. Methods: This is a multicenter, prospective, observational study conducted in northern India from Sept2017-Sept2019. All consecutive patients were tested for Her2neu by standard techniques or next-generation sequencing (NGS). Trastuzumab or Lapatinib was used as the anti Her2 therapy along with chemotherapy. Outcome measures were overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) and compared to historical controls. Data were censored on 31Dec2019. Results: A total of 181 patients were screened; 38 (20.9%) patients were positive for Her2neu or Her3neu. Demographic details are depicted in the table. Her2 was detected by IHC 18 (47%), FISH 6(15.7%) or NGS 14(36.8%). Five patients were positive for Her3 mutation and/or amplification. Twenty-one patients received anti Her2 therapy upfront with chemotherapy. At a median follow-up of 6.8 months, median PFS was 4.1 months for chemotherapy only (n = 85) and 9.7 months for trastuzumab with chemotherapy (n = 21) (HR 0.22; P < 0.05). The median OS was 14 and 6 months in patients with or without trastuzumab-based therapy (HR 0.08 P = 0.001), respectively. Trastuzumab with chemotherapy was well tolerated. Conclusions: Her2neu directed therapy significantly improve ORR, PFS, and OS in GBC with no added toxicities in the first line. It must be evaluated in a randomized phase 3 clinical trials. [Table: see text]

scholarly journals Treatment of Advanced-Stage Large Cell Neuroendocrine Cancer (LCNEC) of the Lung: A Tale of Two Diseases

2021 ◽  
Vol 11 ◽  
Author(s):  
Tahani Atieh ◽  
Chao H. Huang
Keyword(s):  
Progression Free Survival ◽  
Large Cell ◽  
Small Cell ◽  
Advanced Stage ◽  
Limited Data ◽  
Free Survival ◽  
Improved Outcomes ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing ◽  
Optimal Treatment Strategy

LCNEC of the lung comprises a small proportion of pulmonary malignancies. Traditionally, they have been classified based on histologic and immunohistochemistry characteristics with features of small cell and non-small cell lung cancer. The treatment outcome of advanced-stage LCNEC of the lung is poor with response rates ranging from 34 to 46% with platinum doublets, median progression-free survival (mPFS) ranging between 4.4 and 5.8 m, and median overall survival (mOS) ranging from 8 to 12.6 m. The optimal treatment strategy for LCNEC is debated given limited data and different outcomes based on chemotherapy type reported in the available literature. Recently, genomic profiling with Next Generation Sequencing (NGS) has been able to sub-classify LCNEC as SCLC-like or NSCLC-like. Treatment based on this sub-classification has improved outcomes by using SCLC and NSCLC regimens based on their genomic profile in retrospective analysis. Future studies in LCNEC of the lung should incorporate this new molecular sub-classification as stratification and possibly include SCLC-like LCNEC into SCLC studies and NSCLC-like into NSCLC studies.

scholarly journals Circulating Cell-Free Tumor DNA in Advanced Pancreatic Adenocarcinoma Identifies Patients With Worse Overall Survival

2022 ◽  
Vol 11 ◽  
Author(s):  
Gehan Botrus ◽  
Pedro Luiz Serrano Uson Junior ◽  
Puneet Raman ◽  
Adrienne E. Kaufman ◽  
Heidi Kosiorek ◽  
...  
Keyword(s):  
Overall Survival ◽  
Progression Free Survival ◽  
Genomic Alterations ◽  
Free Survival ◽  
Systemic Treatments ◽  
Somatic Alterations ◽  
Next Generation Sequencing Ngs ◽  
The Impact ◽  
Tumor Dna ◽  
Generation Sequencing

BackgroundPlasma-based circulating cell-free tumor DNA (ctDNA) genomic profiling by next-generation sequencing (NGS)is an emerging diagnostic tool for pancreatic cancer (PC). The impact of detected genomic alterations and variant allele fraction (VAF) in tumor response to systemic treatments and outcomes is under investigation.MethodsPatients with advanced PC who had ctDNA profiled at time of initial diagnosis were retrospectively evaluated. We considered the somatic alteration with the highest VAF as the dominant clone allele frequency (DCAF). ctDNA NGS results were related to clinical demographics, progression-free survival (PFS) and overall survival (OS).ResultsA total of 104 patients were evaluated. Somatic alterations were detected in 84.6% of the patients. Patients with ≥ 2 detectable genomic alterations had worse median PFS (p &lt; 0.001) and worse median OS (p = 0.001). KRAS was associated with disease progression to systemic treatments (80.4% vs 19.6%, p = 0.006), worse median PFS (p &lt; 0.001) and worse median OS (p = 0.002). TP53 was associated with worse median PFS (p = 0.02) and worse median OS (p = 0.001). The median DCAF was 0.45% (range 0-55%). DCAF &gt;0.45% was associated with worse median PFS (p&lt;0.0001) and median OS (p=0.0003). Patients that achieved clearance of KRAS had better PFS (p=0.047), while patients that achieved clearance of TP53 had better PFS (p=0.0056) and OS (p=0.037).ConclusionsInitial detection of ctDNA in advanced PC can identify somatic alterations that may help predict clinical outcomes. The dynamics of ctDNA are prognostic of outcomes and should be evaluated in prospective studies.

scholarly journals Treatment of Angiosarcoma with Pazopanib and Paclitaxel: Results of the EVA (Evaluation of Votrient® in Angiosarcoma) Phase II Trial of the German Interdisciplinary Sarcoma Group (GISG-06)

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1223
Author(s):  
Daniel Pink ◽  
Dimosthenis Andreou ◽  
Sebastian Bauer ◽  
Thomas Brodowicz ◽  
Bernd Kasper ◽  
...  
Keyword(s):  
Immune Checkpoint Inhibitors ◽  
Median Overall Survival ◽  
Phase Ii Trial ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Free Survival ◽  
Safety And Efficacy ◽  
Future Studies ◽  
Entire Cohort

We aimed to evaluate the efficacy and toxicity of paclitaxel combined with pazopanib in advanced angiosarcoma (AS). The primary end point was progression-free survival (PFS) rate at six months (PFSR6). Planned accrual was 44 patients in order to detect a PFSR6 of >55%, with an interim futility analysis of the first 14 patients. The study did not meet its predetermined interim target of 6/14 patients progression-free at 6 months. At the time of this finding, 26 patients had been enrolled between July 2014 and April 2016, resulting in an overrunning of 12 patients. After a median follow-up of 9.5 (IQR 7.7–15.4) months, PFSR6 amounted to 46%. Two patients had a complete and seven patients a partial response. Patients with superficial AS had a significantly higher PFSR6 (61% vs. 13%, p = 0.0247) and PFS (11.3 vs. 2.7 months, p < 0.0001) compared to patients with visceral AS. The median overall survival in the entire cohort was 21.6 months. A total of 10 drug-related serious adverse effects were reported in 5 patients, including a fatal hepatic failure. Although our study did not meet its primary endpoint, the median PFS of 11.6 months in patients with superficial AS appears to be promising. Taking recent reports into consideration, future studies should evaluate the safety and efficacy of VEGFR and immune checkpoint inhibitors with or without paclitaxel in a randomized, multiarm setting.

Evolution of Surgical Approaches in the Treatment of Petroclival Meningiomas: A Retrospective Review

2007 ◽  
Vol 61 (suppl_5) ◽  
pp. ONS202-ONS211 ◽  
Author(s):  
Nicholas C. Bambakidis ◽  
U. Kumar Kakarla ◽  
Louis J. Kim ◽  
Peter Nakaji ◽  
Randall W. Porter ◽  
...  
Keyword(s):  
Survival Rates ◽  
Progression Free Survival ◽  
Surgical Approaches ◽  
Single Institution ◽  
Short Term ◽  
Total Resection ◽  
Free Survival ◽  
Petroclival Meningioma ◽  
Petroclival Meningiomas

Abstract Objective: We examined the surgical approaches used at a single institution to treat petroclival meningioma and evaluated changes in method utilization over time. Methods: Craniotomies performed to treat petroclival meningioma between September of 1994 and July of 2005 were examined retrospectively. We reviewed 46 patients (mean follow-up, 3.6 yr). Techniques included combined petrosal or transcochlear approaches (15% of patients), retrosigmoid craniotomies with or without some degree of petrosectomy (59% of patients), orbitozygomatic craniotomies (7% of patients), and combined orbitozygomatic-retrosigmoid approaches (19% of patients). In 18 patients, the tumor extended supratentorially. Overall, the rate of gross total resection was 43%. Seven patients demonstrated progression over a mean of 5.9 years. No patients died. At 36 months, the progression-free survival rate for patients treated without petrosal approaches was 96%. Of 14 patients treated with stereotactic radiosurgery, none developed progression. Conclusion: Over the study period, a diminishing proportion of patients with petroclival meningioma were treated using petrosal approaches. Utilization of the orbitozygomatic and retrosigmoid approaches alone or in combination provided a viable alternative to petrosal approaches for treatment of petroclival meningioma. Regardless of approach, progression-free survival rates were excellent over short-term follow-up period.

scholarly journals FAS and Subsequent Therapies in Pancreatic Neuroendocrine Tumors

2021 ◽  
Author(s):  
Jane E. Rogers ◽  
Michael Lam ◽  
Daniel M. Halperin ◽  
Cecile G. Dagohoy ◽  
James C. Yao ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Pancreatic Neuroendocrine Tumors ◽  
Free Survival ◽  
Prior Therapy ◽  
Well Differentiated ◽  
Grade 3 ◽  
Line Of Therapy

We evaluated outcomes of treatment with 5-fluorouracil (5-FU), doxorubicin, and streptozocin (FAS) in well-differentiated pancreatic neuroendocrine tumors (PanNETs) and its impact on subsequent therapy (everolimus or temozolomide). Advanced PanNET patients treated at our center from 1992 to 2013 were retrospectively reviewed. Patients received bolus 5-FU (400 mg/m2), streptozocin (400 mg/m2) (both IV, days 1-5) and doxorubicin (40 mg/m2 IV, day 1) every 28 days. Overall response rate (ORR) was assessed using RECIST version 1.1. Of 243 eligible patients, 220 were evaluable for ORR, progression-free survival (PFS), and toxicity. Most (90%) had metastatic, nonfunctional PanNETs; 14% had prior therapy. ORR to FAS was 41% (95% confidence interval [CI]: 36-48%). Median follow-up was 61 months. Median PFS was 20 (95% CI: 15-23) months; median overall survival (OS) was 63 (95% CI: 60-71) months. Cox regression analyses suggested improvement with first-line vs subsequent lines of FAS therapy. Main adverse events ≥ grade 3 were neutropenia (10%) and nausea/vomiting (5.5%). Dose reductions were required in 32% of patients. Post-FAS everolimus (n=108; 68% second line) had a median PFS of 10 (95% CI: 8-14) months. Post-FAS temozolomide (n=60; 53% > fourth line) had an ORR of 13% and median PFS of 5.2 (95% CI: 4-12) months. In this largest reported cohort of PanNETs treated with chemotherapy, FAS demonstrated activity without significant safety concerns. FAS did not appear to affect subsequent PFS with everolimus; this sequence is being evaluated prospectively. Responses were noted with subsequent temozolomide-based regimens although PFS was possibly limited by line of therapy.

scholarly journals Cetuximab versus bevacizumab following prior FOLFOXIRI and bevacizumab in postmenopausal women with advanced KRAS and BRAF wild-type colorectal cancer: a retrospective study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chunlong Huang ◽  
Xiaoyuan Gu ◽  
Xianshang Zeng ◽  
Baomin Chen ◽  
Weiguang Yu ◽  
...  
Keyword(s):  
Postmenopausal Women ◽  
Survival Benefit ◽  
Progression Free Survival ◽  
Wild Type ◽  
Free Survival ◽  
Primary Endpoints ◽  
Significant Difference ◽  
Inductive Treatment ◽  
Advanced Colorectal Carcinoma

Abstract Background An upgraded understanding of factors (sex/estrogen) associated with survival benefit in advanced colorectal carcinoma (CRC) could improve personalised management and provide innovative insights into anti-tumour mechanisms. The aim of this study was to assess the efficacy and safety of cetuximab (CET) versus bevacizumab (BEV) following prior 12 cycles of fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus BEV in postmenopausal women with advanced KRAS and BRAF wild-type (wt) CRC. Methods Prospectively maintained databases were reviewed from 2013 to 2017 to assess postmenopausal women with advanced KRAS and BRAF wt CRC who received up to 12 cycles of FOLFOXIRI plus BEV inductive treatment, followed by CET or BEV maintenance treatment. The primary endpoints were overall survival (OS), progression-free survival (PFS), response rate. The secondary endpoint was the rate of adverse events (AEs). Results At a median follow-up of 27.0 months (IQR 25.1–29.2), significant difference was detected in median OS (17.7 months [95% confidence interval [CI], 16.2–18.6] for CET vs. 11.7 months [95% CI, 10.4–12.8] for BEV; hazard ratio [HR], 0.63; 95% CI, 0.44–0.89; p=0.007); Median PFS was 10.7 months (95% CI, 9.8–11.3) for CET vs. 8.4 months (95% CI, 7.2–9.6) for BEV (HR, 0.67; 95% CI 0.47–0.94; p=0.02). Dose reduction due to intolerable AEs occurred in 29 cases (24 [24.0%] for CET vs. 5 [4.8%] for BEV; p< 0.001). Conclusions CET tends to be superior survival benefit when compared with BEV, with tolerated AEs.

Prognostic Relevance of Celiac Lymph Node Involvement in Ovarian Cancer

2014 ◽  
Vol 24 (1) ◽  
pp. 48-53 ◽  
Author(s):  
Alejandra Martínez ◽  
Cristophe Pomel ◽  
Thomas Filleron ◽  
Marjolein De Cuypere ◽  
Eliane Mery ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Lymph Node ◽  
Oncologic Outcome ◽  
Progression Free Survival ◽  
Disease Spread ◽  
Short Term ◽  
Free Survival ◽  
Increased Risk

ObjectiveThe aim of the study was to report on the oncologic outcome of the disease spread to celiac lymph nodes (CLNs) in advanced-stage ovarian cancer patients.MethodsAll patients who had CLN resection as part of their cytoreductive surgery for epithelial ovarian, fallopian, or primary peritoneal cancer were identified. Patient demographic data with particular emphasis on operative records to detail the extent and distribution of the disease spread, lymphadenectomy procedures, pathologic data, and follow-up data were included.ResultsThe median follow-up was 26.3 months. The median overall survival values in the group with positive CLNs and in the group with negative CLNs were 26.9 months and 40.04 months, respectively. The median progression-free survival values in the group with metastatic CLNs and in the group with negative CLNs were 8.8 months and 20.24 months, respectively (P = 0.053). Positive CLNs were associated with progression during or within 6 months after the completion of chemotherapy (P = 0.0044). Tumor burden and extensive disease distribution were significantly associated with poor progression-free survival, short-term progression, and overall survival. In multivariate analysis, only the CLN status was independently associated with short-term progression.ConclusionsDisease in the CLN is a marker of disease severity, which is associated to a high-risk group of patients with presumed adverse tumor biology, increased risk of lymph node progression, and worst oncologic outcome.

scholarly journals CTNI-63. PROGNOSTIC FACTORS IN PATIENTS WITH BASAL GANGLIA GERM-CELL TUMORS: A RETROSPECTIVE ANALYSIS OF THE SINGLE CHINESE INSTITUTE EXPERIENCE FROM 2009 TO 2019

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii57-ii57
Author(s):  
Qingjun Hu ◽  
Juan Li ◽  
Mingyao Lai ◽  
Cheng Zhou ◽  
Zhaoming Zhou ◽  
...  
Keyword(s):  
Survival Rate ◽  
Basal Ganglia ◽  
Germ Cell ◽  
Retrospective Analysis ◽  
Surgical Resection ◽  
Germ Cell Tumors ◽  
Progression Free Survival ◽  
Course Of Disease ◽  
Free Survival

Abstract OBJECTIVE To evaluate the clinical factors related to the prognosis of basal ganglia germ cell tumors. METHODS A retrospective analysis of 52 cases of the basal ganglia germ cell tumors treated from January 2009 to January 2019 in the department of oncology of Guangdong Sanjiu Brain Hospital. The median age: 12 years (range: 5–32), The median course of disease: 11.7 months (range: 1–54). Thirteen cases were diagnosed by biopsy and 39 cases were diagnosed by elevated tumor markers. There were 31 patients (59.6%) diagnosed with germinomas and 21 patients (40.4%) with non-germ germ cell tumors. Univariate and multivariate survival analysis was performed. RESULTS To October 15, 2019, the median follow-up time was 30.4 months (range 2–124 months). The 5-year survival rate was 85%, and the 5-year progression-free survival rate was 84%. Multivariate analysis found whether serum AFP was greater than 100mIU / ml, (with HR: 11.441,95% CI: 2.09–47.66, P = 0.005),the degree of surgical resection(with HR 5.323 (1.19–23.812), P = 0.029), PD as the effect of radiotherapy (HR: 16.53, (1.19–23.81), P = 0.001) were independent prognostic factor affecting survival. CONCLUSION The pathological type, degree of surgical resection, and response to initial treatment can all affect survival.

KAI-1 Expression in Pediatric High-Grade Osteosarcoma

2006 ◽  
Vol 9 (3) ◽  
pp. 219-224 ◽  
Author(s):  
Patrick J. Leavey ◽  
Charles Timmons ◽  
William Frawley ◽  
Donald Lombardi ◽  
Raheela Ashfaq
Keyword(s):  
Prognostic Markers ◽  
Clinical Phenotype ◽  
Tumor Resection ◽  
Progression Free Survival ◽  
Surface Proteins ◽  
High Grade ◽  
Free Survival ◽  
Treatment Groups ◽  
High Grade Osteosarcoma

Recent evidence implicates cell surface proteins of the tetraspanin superfamily in the process of metastasis whereas the downregulation of KAI-1, a member of the tetraspanin family, is associated with an aggressive clinical phenotype in several types of human cancers. To determine if expression of KAI-1-1 is associated with any known prognostic marker or clinical outcome in high-grade osteosarcoma, we examined 91 nondecalcified archival samples from 47 patients for the expression of KAI-1. Archival, paraffin-embedded, and decalcified pathologic samples were examined by immunohistochemistry and results were correlated to clinical outcomes and known prognostic markers. There were 46 samples from diagnostic biopsies (1 diagnostic sample was not available), 32 tumor resection samples, and 13 metastasis samples. Thirty-three percent (n = 30) of the samples expressed KAI-1 (16 biopsies, 9 resections, and 5 metastasis). KAI-1 expression was not significantly related to known prognostic markers or to either tumor necrosis after neoadjuvant therapy or the incidence of metastasis at diagnosis. KAI-1 expression was not significantly different between paired diagnostic tumor samples and either resection or metastasis tumor samples. Twenty-five patients remain alive at a median follow-up of 95 months. The overall and progression-free survival percentages at 5 years were 62% and 47% for KAI-1-positive patients and 49% and 38% for KAI-1-negative patients, respectively. This difference was not statistically significant. We conclude that KAI-1 is expressed in a proportion of high-grade osteosarcoma but is not of clinical significance and cannot be used to stratify treatment groups for these patients.

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