Molecular profile of ampulla of vater carcinoma (AVC): A rare tumor type with meaningful molecular alterations.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4119-4119
Author(s):  
João Pinto ◽  
Helena Verdaguer ◽  
Maria Teresa Salcedo ◽  
Anna Pedrola ◽  
Jorge Hernando-Cubero ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Stage Iv ◽  
Molecular Profile ◽  
Tumor Type ◽  
Phase I Clinical Trials ◽  
Histological Subtypes ◽  
Rare Type ◽  
Molecular Alterations ◽  
Dismal Prognosis ◽  
Stage Iv Disease

4119 Background: AVC is a rare type of cancer with dismal prognosis and limited therapeutic options due to the lack of specific clinical trials. Two histologic subtypes predominate, namely pancreatobiliary and intestinal. A variety of molecular alterations have been described in AVC, but their clinical and therapeutic implications have not been studied in detail. Methods: Retrospective cohort study of patients (pts) diagnosed with AVC treated in our institution from 2010 to 2018. We routinely performed Next Generation Sequencing in all AVC tumors. Our main objectives were to describe the molecular profile of AVC and correlate with clinical outcomes. Results: Out of 26 pts with AVC, 13 pts were male (50%), median age 65 (range 43-83), 7 pts (27%) had stage IV disease at diagnosis. Histologic type was pancreatobiliary in 18 pts (69%), intestinal in 7 pts (27%) and mixed in one case (4%). We identified KRAS mutations (mut) in 10 pts (7 pancreatobiliary, 2 intestinal, 1 mixed), TP53 mut in 6 pts (4/1/1), PIK3CA mut in 3 pts (3/0/0), ERBB2 mut in 3 pts (2/1/0), CTNNB1 mut in 3 pts (2/1/0). In pancreatobiliary we found single cases with RNF43, BRCA1 and CHEK2 mut; while in intestinal we found single cases with NRAS and BRAF mut. One tumor of intestinal subtype had microsatellite instability (MSI). Three pts were included in phase I clinical trials, 2 of them with trials based on tumor profile (ERBB2 mut with pan-HER inhibitor and MSI with immunotherapy). Median overall survival (OS) was 21 months for pts with stage I, II and III disease (95% CI 12.37-not reached) and 13.2 months for stage IV disease at diagnosis (95% CI 5.73-not reached). In cox models, median OS was not dependent on KRAS or TP53 mutation status, or histological subtypes. Conclusions: AVC is a rare type of cancer with two differentiated histological subtypes harboring unique molecular alterations that can be matched to investigational therapies. A broader knowledge of the biology of these tumors is needed to improve patient outcomes.

scholarly journals Molecular diagnostics helps to identify distinct subgroups of spinal astrocytomas

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Annamaria Biczok ◽  
Felix L. Strübing ◽  
Julia M. Eder ◽  
Rupert Egensperger ◽  
Oliver Schnell ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Molecular Markers ◽  
Prognostic Significance ◽  
The Elderly ◽  
Molecular Profile ◽  
Diffuse Astrocytoma ◽  
Molecular Alterations ◽  
High Grade Astrocytoma ◽  
Dismal Prognosis ◽  
Few Data

AbstractPrimary spinal cord astrocytomas are rare, hence few data exist about the prognostic significance of molecular markers. Here we analyze a panel of molecular alterations in association with the clinical course. Histology and genome sequencing was performed in 26 spinal astrocytomas operated upon between 2000 and 2020. Next-generation DNA/RNA sequencing (NGS) and methylome analysis were performed to determine molecular alterations. Histology and NGS allowed the distinction of 5 tumor subgroups: glioblastoma IDH wildtype (GBM); diffuse midline glioma H3 K27M mutated (DMG-H3); high-grade astrocytoma with piloid features (HAP); diffuse astrocytoma IDH mutated (DA), diffuse leptomeningeal glioneural tumors (DGLN) and pilocytic astrocytoma (PA). Within all tumor entities GBM (median OS: 5.5 months), DMG-H3 (median OS: 13 months) and HAP (median OS: 8 months) showed a fatal prognosis. DMG-H3 tend to emerge in adolescence whereas GBM and HAP develop in the elderly. HAP are characterized by CDKN2A/B deletion and ATRX mutation. 50% of PA tumors carried a mutation in the PIK3CA gene which is seemingly associated with better outcome (median OS: PIK3CA mutated 107.5 vs 45.5 months in wildtype PA). This exploratory molecular profiling of spinal cord astrocytomas allows to identify distinct subgroups by combining molecular markers and histomorphology. DMG-H3 tend to develop in adolescence with a similar dismal prognosis like GBM and HAP in the elderly. We here describe spinal HAP with a distinct molecular profile for the first time.

Safety and efficacy of the combination carboplatin and paclitaxel in patients (pts) with recurrent head and neck squamous cell carcinoma (HNSCC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 15534-15534
Author(s):  
D. Ferrari ◽  
A. Rocca ◽  
S. Oldani ◽  
F. Zannier ◽  
T. Tartaro ◽  
...  
Keyword(s):  
Side Effects ◽  
Head And Neck ◽  
Treatment Options ◽  
Stage Iv ◽  
Complete Response ◽  
Hematologic Toxicity ◽  
Dismal Prognosis ◽  
Stage Iv Disease ◽  
Previously Treated ◽  
Darbepoetin Alpha

15534 Background: Pts with recurrent HNSCC have a dismal prognosis; treatment options are poorly effective and burdened with toxicity. In this clinical setting, cisplatin and paclitaxel have demonstrated activity despite relevant side effects. The purpose of this phase II trial was to investigate whether a combination of carboplatin and paclitaxel could offer a better toxicity profile without affecting efficacy. Methods: Pts with bi-dimensionally measurable disease, previously treated with induction chemotherapy (Cisplatin and 5-FU) followed by concomitant chemo-radiotherapy, were studied. Treatment consisted of Carboplatin AUC 5 and Paclitaxel 175 mg/m2 intravenously every 3 weeks. G-CSF and darbepoetin alpha were allowed in case of neutropenia (N < 1000/mm3) or anemia (Hb < 11 g/dL). Pts were evaluated for toxicity and response. Results: So far, 15 pts were enrolled. Median age was 53 yrs; ECOG P.S. was 0–1. Site of disease at relapse was head and neck excluding lips and sinus; 12 out of 15 pts had stage IV disease. All pts were evaluated for response and toxicity. After three cycles of chemotherapy, we observed 1 complete response (6.6%) and 7 partial responses (46.6%), with a 53.2 % overall response rate (95% CI 26.6–78.7%). Stable disease was seen in 2 patients (13.3%) and progressive disease was observed in 5 pts (33.3%). Toxicity was mild: we recorded 1 case of G3 toxicity (neutropenia) and no G4 side effects. Three pts experienced G1–2 neuropathy and 4 pts G1–2 hematologic toxicity (neutropenia and thrombocytopenia). Conclusions: The current regimen was feasible and effective. The combination of Carboplatin and Paclitaxel was well tolerated and could be safely administered to pts with recurrent HNSCC as second line treatment. Enrollment and data collection are still ongoing. No significant financial relationships to disclose.

Personalized medicine in a phase I clinical trials program: The M. D. Anderson Cancer Center Initiative.

2011 ◽  
Vol 29 (18_suppl) ◽  
pp. CRA2500-CRA2500 ◽  
Author(s):  
A. M. Tsimberidou ◽  
N. G. Iskander ◽  
D. S. Hong ◽  
J. J. Wheler ◽  
S. Fu ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Targeted Therapy ◽  
Personalized Medicine ◽  
Phase I ◽  
Molecular Analysis ◽  
Pik3ca Mutation ◽  
Molecular Profile ◽  
Cancer Center ◽  
Molecular Testing ◽  
Phase I Clinical Trials

CRA2500 Background: We initiated a personalized medicine program hypothesizing that tumor molecular analysis and use of targeted therapy to counteract the effects of specific aberrations would improve the outcomes of affected patients. Methods: Molecular analysis was performed in the M. D. Anderson CLIA-certified pathology laboratory. Patients whose tumors had an aberration were treated in the Phase I Program with a matched targeted agent, when available. Results: Tumor molecular analysis was feasible in 852 (89%) of 955 consecutive patients with advanced cancer. Of 852 patients (median, age 56 yrs; prior therapies 4), 354 (41.5%) had ≥ 1 aberration: 10% of patients had a PIK3CA mutation; 19% KRAS; 8% NRAS; 19% BRAF; 3% EGFR; and 2% had a CKIT mutation; 21% had PTEN loss. Results are shown in the table. Median time to treatment failure (TTF) in 161 patients with 1 aberration treated with matched targeted therapy was 5.3 months (95%CI: 4.1, 6.6) vs 3.2 months (95%CI: 2.9 – 4.0) for their prior systemic antitumor therapy (prior to referral to phase I) (p= .0003). For patients with 1 aberration, the CR+PR rate was 29% with matched targeted therapy vs. 8% without matching (p = .0001). The CR+PR rate was 6% in 438 patients without molecular testing treated on the same studies. Conclusions: Preliminary results suggest that in early clinical trials matching patients with targeted drugs based on their molecular profile results in (a) longer TTF compared to their prior therapy and (b) higher rates of response, survival and TTF compared to those seen in patients treated without molecular matching. Support: 3UL1 RR024148 04 S1 and IPCT. [Table: see text]

Predictors of survival in pancreatic squamous cell carcinoma (PSCC): An analysis from the National Cancer Database (NCDB).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 399-399
Author(s):  
Anuhya Kommalapati ◽  
Sri Harsha Tella ◽  
Gaurav Goyal ◽  
Amit Mahipal
Keyword(s):  
Surgical Resection ◽  
Primary Tumor ◽  
Multivariable Analysis ◽  
Group Analysis ◽  
Stage Iv ◽  
The United States ◽  
Stage I ◽  
Stage Iii ◽  
Dismal Prognosis ◽  
Stage Iv Disease

399 Background: PSCC is a rare form of exocrine pancreatic malignancy with a dismal prognosis. Using the NCDB, we determined the prognostic factors and survival outcomes of PSCC in the United States. Methods: We performed a retrospective analysis of patients with histologically confirmed PSCC from 2004-2015 using NCDB. Kaplan-Meier method and log-rank test were used to perform overall survival (OS) analysis. Hazard Ratios were calculated using the Cox-proportional hazard method. Results: Of the 654 cases included in our analysis, 46% were female. Median age at diagnosis was 70 years and did not differ by sex (p = 0.19). The proportion of patients with stage I, II, III and IV diseases were 5%, 18%, 12%, and 54%, respectively (10%, unknown stage). Among these, 23% (35 of 150) of stage I and II disease, 10% (8 of 78) of stage III, and 2% (7 of 353) received surgical resection of the primary tumor. The rate of R0 resection was 74% in stage I and II; 38% in stage III; 29% in stage IV disease. Median OS for the entire cohort was 4 months and was significantly higher in patients who received surgical resection of the primary tumor (17 vs. 4 months, p < 0.001). On stage wise sub-group analysis, stage I-II patients had OS benefit from surgery (21 vs. 5 months, p < 0.001) as opposed to stage III (7 vs. 6 months, p = 0.31) and IV disease (5 vs. 3 months, p = 0.17). Adjuvant chemotherapy had no role in prolonging survival in stage I-II disease (20 vs 24 months, p = 0.6). Stage IV patients treated with chemotherapy had a better median OS than those without (5 vs. 2 months, p < 0.0001). On Cox multivariable analysis, stage IV disease (HR: 1.92 CI: 1.46-2.52, p < 0.001) and advanced patient age (HR: 1.02; CI:1.01-1.03, p < 0.001 were associated with poor OS, whereas OS was not dependent on the sex, race, grade, insurance status, surgery, and chemotherapy. Conclusions: This is the largest registry-based study on PSCC to date. PSCC had a diverse OS varied significantly according to increasing age and stage of the disease at presentation. Surgical resection of primary tumor was associated with improved OS in stages I-II, whereas chemotherapy improved OS in stage IV disease. The results of our study may aid the prognostication of patients and in treatment decision making.

scholarly journals P13.14 Use of Foundation one CDx for molecular screening in patients with primary brain tumors: Gustave Roussy Experience

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii65-iii65
Author(s):  
C Baldini ◽  
W Boulfoul ◽  
L Lacroix ◽  
E Rouleau ◽  
J Scoazec ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Brain Tumors ◽  
Tumor Tissue ◽  
Therapeutic Strategies ◽  
Braf V600e ◽  
Tumor Type ◽  
Molecular Screening ◽  
Primary Brain Tumors ◽  
Molecular Alterations ◽  
Multidisciplinary Meeting

Abstract BACKGROUND Patients with primary brain tumors usually have poor prognosis and few therapeutic options. However recent report showed that they may benefit from molecular screening to improve treatment benefit and enrollment in clinical trials. We aimed to evaluate if molecular screening using Foundation One Dx may help therapeutic strategies in primary brain tumor patients. MATERIAL AND METHODS Between October 2018 and December 2018, we enrolled prospectively patients in the MOSCATO (Molecular Screening for cancer Treatment Optimization) 02 trial using the Foundation One Dx test. Patients were eligible if they had good Performans status (PS) (0 or 1) and tumor tissue material available. Results were reviewed during a molecular multidisciplinary meeting weekly at the Drug Development Department at Gustave Roussy to decide on orientation and matched therapy according to molecular alterations. RESULTS Finally thirty-three patients were enrolled in the study. Twenty six tumor tissues were analysed and 7 patients were screen failures due to tumor tissue unavailability. Median age was 49 years old (19 - 72). Patients had a good PS with a median of 1 (0–2) and were mostly males (76%). The most common tumor type was glioblastoma (79%). Five patients had a high grade tumor including 2 medulloblastomas. Median time between consent and multidisciplinary meeting was 70 days (49 - 156). Median percentage of tumor cells was 78% (30–80%). The tumor mutational burden (TMB) was available in 26 patients. The median TMB was 4 mutations per megabase (0 - 277). The most frequent alterations were TERT promoter mutation 22/26 (85%), CDKN2A loss 14/26 (54%), MTAP loss 11/26 (42%), EGFR amplification (38%) including 4 EGFRvIII amplification, TP53 mutation and PTEN deletion 9/26 (35%) respectively, PIK3CA mutation 5/26 (19%), CDK4 or 6 amplification 4/26 (15%), NF1 mutation 3/26 (12%), 2 IDH1 mutations, 2 MET amplifications, 2 HGF amplifications, 1 FGFR2 mutation, 1 BRAF V600E mutation, 1 PDGFRA amplification, 1 EZH2 mutation and 1 SMARCA4 mutation. Finally 11 patients (42%) were oriented according to molecular alterations (EGFR amplifications, BRAF mutation), 1 patient was treated and is ongoing with a BRAF inhibitor and 1 patient is in screening in atrial with an EGFR inhibitor. CONCLUSION Molecular screening with Foundation One Dx test is feasible in patients with primary brain tumors and can help therapeutic strategies. However the time between consent and multidisciplinary meeting was the main limitation to our study and affected enrollment in clinical trials.

scholarly journals Targeted Therapy Recommendations for Therapy Refractory Solid Tumors—Data from the Real-World Precision Medicine Platform MONDTI

2020 ◽  
Vol 10 (4) ◽  
pp. 188
Author(s):  
Hossein Taghizadeh ◽  
Matthias Unseld ◽  
Martina Spalt ◽  
Robert M. Mader ◽  
Leonhard Müllauer ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Precision Medicine ◽  
Solid Tumors ◽  
Real World ◽  
Molecular Profile ◽  
Tumor Type ◽  
Therapy Recommendations ◽  
Dismal Prognosis ◽  
Advanced Therapy ◽  
Therapy Recommendation

Advanced therapy-refractory solid tumors bear a dismal prognosis and constitute a major challenge in offering effective treatment strategies. In this real-world retrospective analysis of our precision medicine platform MONDTI, we describe the molecular profile of 554 patients diagnosed with 17 different types of advanced solid tumors after failure of all standard treatment options. In 304 cases (54.9% of all patients), a molecular-driven targeted therapy approach could be recommended, with a recommendation rate above 50% in 12 tumor entities. The three highest rates for therapy recommendation per tumor classification were observed in urologic malignancies (90.0%), mesothelioma (78.6%), and male reproductive cancers (71.4%). Tumor type (p = 0.46), expression of p-mTOR (p = 0.011), expression of EGFR (p = 0.046), and expression of PD-L1 (p = 0.023) had a significant impact on the targeted therapy recommendation rate. Therapy recommendations were significantly more often issued for men (p = 0.015) due to gender-specific differences in the molecular profiles of patients with head and neck cancer and malignant mesothelioma. This analysis demonstrates that precision medicine was feasible and provided the basis for molecular-driven therapy recommendations in patients with advanced therapy refractory solid tumors.

Decreased enrollment of patients with advanced lobular breast cancer compared to ductal breast cancer in interventional clinical trials.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1092-1092
Author(s):  
Mary Kathryn Abel ◽  
Michelle E. Melisko ◽  
Hope S. Rugo ◽  
Amy Jo Chien ◽  
Italia Diaz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
San Francisco ◽  
Cancer Registry ◽  
Ductal Carcinoma ◽  
Stage Iv ◽  
Tumor Type ◽  
Early Stage Disease ◽  
Stage Iv Breast Cancer ◽  
Measurable Disease

1092 Background: Response Evaluation Criteria in Solid Tumors (RECIST) criteria are often used to measure tumor response in cancer trials, especially in the stage IV setting. However, RECIST requires measurable disease, which is less common in invasive lobular breast carcinoma (ILC) of the breast, a diffusely growing tumor type, compared to invasive ductal carcinoma (IDC). We examined the prevalence of RECIST in breast cancer clinical trials, and whether there are differential trial enrollment rates by histology and stage. Methods: We analyzed the clinicaltrials.gov database to evaluate the proportion of interventional, stage IV clinical trials that require measurable disease as inclusion criteria or outcome measures. We then performed an institutional cohort study comparing the proportion of patients in the University of California, San Francisco (UCSF) OnCore clinical trials management system (CTMS) to the UCSF Cancer Registry between 2000-2018, stratified by histology and stage. We hypothesized that the proportion of patients with ILC in the CTMS would be significantly lower than in the cancer registry. Results: There were 146 actively-recruiting, interventional clinical trials for stage IV breast cancer that were identified in our search on clinicaltrials.gov. Overall, 108 (74%) required measurable disease for study participation. The UCSF Cancer Registry included 8,679 patients, while the UCSF OnCore CTMS included 1,511 patients (Table). In those with early stage disease, where RECIST is not typically used, there was no difference in the proportion of ILC patients enrolled in clinical trials versus in the cancer registry. However, among those with stage IV disease, there was a significantly lower proportion of patients with ILC in the CTMS than in the cancer registry (9.2% versus 17.9%, p = 0.005). In contrast, patients with stage IV IDC were overrepresented in the clinical trials database compared to the cancer registry. Conclusions: Patients with metastatic ILC were significantly less likely to be enrolled in clinical trials than those with metastatic IDC. This decreased enrollment may be due to the widespread use of RECIST, and further investigation is needed to ensure equity in access to clinical trials.[Table: see text]

scholarly journals Metastatic Uveal Melanoma: Treatment Strategies and Survival—Results from the Dutch Melanoma Treatment Registry

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1007 ◽  
Author(s):  
Anouk Jochems ◽  
Monique K. van der Kooij ◽  
Marta Fiocco ◽  
Maartje G. Schouwenburg ◽  
Maureen J. Aarts ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Uveal Melanoma ◽  
Treatment Options ◽  
Survival Rates ◽  
Real Life ◽  
Treatment Strategies ◽  
Stage Iv ◽  
Lactate Dehydrogenase Level ◽  
Stage Iv Disease ◽  
Melanoma Treatment

Uveal melanoma (UM) is the most common primary intraocular tumor in adults. Up to 50% of UM patients will develop metastases. We present data of 175 metastatic UM patients diagnosed in the Netherlands between July 2012 and March 2018. In our cohort, elevated lactate dehydrogenase level (LDH) is an important factor associated with poorer survival (Hazard Ratio (HR) 9.0, 95% Confidence Interval (CI) 5.63–14.35), and the presence of liver metastases is negatively associated with survival (HR 2.09, 95%CI 1.07–4.08). We used data from the nation-wide Dutch Melanoma Treatment Registry (DMTR) providing a complete overview of the location of metastases at time of stage IV disease. In 154 (88%) patients, the liver was affected, and only 3 patients were reported to have brain metastases. In 63 (36%) patients, mutation analysis was performed, showing a GNA11 mutation in 28.6% and a GNAQ mutation in 49.2% of the analyzed patients. In the absence of standard care of treatment options, metastatic UM patients are often directed to clinical trials. Patients participating in clinical trials are often subject to selection and usually do not represent the entire metastatic UM population. By using our nation-wide cohort, we are able to describe real-life treatment choices made in metastatic UM patients and 1-year survival rates in selected groups of patients.

scholarly journals Predictors for thromboembolism in patients with cholangiocarcinoma

2021 ◽  
Author(s):  
Christian Pfrepper ◽  
Maren Knödler ◽  
Ruth Maria Schorling ◽  
Daniel Seehofer ◽  
Sirak Petros ◽  
...  
Keyword(s):  
Patient Population ◽  
Multivariable Analysis ◽  
Stage Iv ◽  
Cancer Center ◽  
First Year ◽  
Thromboembolic Events ◽  
Rare Type ◽  
Increased Risk ◽  
Stage Iv Disease ◽  
Portal Venous Thrombosis

Abstract Background Patients with cancer are at increased risk of thromboembolic events contributing significantly to cancer-related morbidity and mortality. Because cholangiocarcinoma is a rare type of cancer, the incidence of thromboembolism in this patient population is not well defined. Methods Patients with cholangiocarcinoma treated at the University Cancer Center Leipzig between January 2014 and December 2018 were analyzed retrospectively regarding the incidence of arterial and venous thromboembolism. Results A total of 133 newly and consecutively diagnosed patients were included, of whom 22% had stage IV disease. Thromboembolism was diagnosed in 39 (29.3%), with 48% of the events occurring between 60 days prior and 30 days after the initial diagnosis. Arterial thrombosis accounted for 19% and portal venous thrombosis for 33% of the events, while the rest of events occurred in the non-portal venous system. In multivariable analysis, an ONKOTEV score ≥ 2 was the only independent predictor for thromboembolism. Serum CA 19-9 was available in 87 patients (65.4%). In this subgroup, CA 19-9 above the median of 97.7 U/ml and vascular or lymphatic compression were independent predictors for thromboembolism in the first year and CA 19-9 alone remained a significant predictor over the whole observation period. An ONKOTEV score ≥ 2 and increasing age were predictors of survival. Conclusions A very high thromboembolic risk was observed in cholangiocarcinoma, comparable to the risk situation in pancreatic and gastric cancer. The ONKOTEV score and serum CA 19-9 are independent predictors of thromboembolic events. Prospective validation of our observations in this patient population is warranted.

Sign in / Sign up

Export Citation Format

Share Document