Predictors of treatment response in colorectal high-grade neuroendocrine carcinomas (HGNEC): A single institution experience.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 690-690
Author(s):  
Virginia Corbett ◽  
Nitya Prabhakar Raj ◽  
Virginia Kelly ◽  
Diane Lauren Reidy
Keyword(s):  
Treatment Options ◽  
Locally Advanced ◽  
Molecular Data ◽  
Molecular Characteristics ◽  
High Grade ◽  
Molecular Alterations ◽  
Predictors Of Response ◽  
Significant Difference ◽  
Molecular Sequencing ◽  
Neuroendocrine Carcinomas

690 Background: Colorectal high-grade neuroendocrine carcinomas (HGNEC) are aggressive tumors; treatment options consist of cis/carboplatin and 5FU-based chemotherapy. To date, choice of systemic therapy and sequencing of these drugs remains poorly understood. We examined clinical and molecular characteristics of colorectal HGNEC to better define predictors of response to cis/carboplatin and 5FU-based treatment. Methods: Patients (pts) with colorectal HGNEC treated at MSKCC from 1990-2018 were identified. MANEC (mixed adeno-neuroendocrine carcinoma) were excluded. Demographics, response to first- and second-line chemotherapy (by radiology report), outcomes, and molecular data (next-generation sequencing of tumor tissue), were collected. Results: 65 pts (mean age 58, 52% male) were identified, 13 (20%) with small cell carcinomas. 52 (79%) metastatic, 13 (20%) locally advanced. 27 (42%) received surgery and 11 (17%) received radiation. 56 pts received cis/carboplatin-based therapy, partial response (PR) in 18 (32%), stable disease (SD) in 4 (7%), and progressive disease (PD) in 31 (55%); 3 (5%) did not tolerate therapy. 28 pts received 5FU-based therapy, 13 PR in (46%), SD in 6 (21%), and PD in 7 (25%); 2 (7%) did not tolerate therapy. Median overall survival was 11.4 months. 21/65 (32%) pts underwent molecular sequencing of tumor; the most common alterations were KRAS 11 (52%), TP53 13 (62%), BRAF 7 (33%), APC 8 (38%), RB1 7 (33%). Most tumors (13/21, 62%) harbored alterations in genes traditionally altered in colorectal adenocarcinoma (KRAS/BRAF/APC) and in HGNEC (TP53/RB1). There was no significant difference in response to cis/carboplatin or 5FU-based chemotherapy based on location of the primary tumor (right vs. left) (p = 0.69/0.85), histologic features of the disease (p = 0.71/0.87), and for response to cis/carboplatin by molecular alterations in KRAS (p = 0.94), BRAF (p = 0.24), APC (p = 0.28), TP53 (p = 0.58), or RB1 (p = 0.28). Conclusions: Colorectal HGNEC are highly aggressive and more effective therapies are desperately needed. In this series, OS was poor. Clinical and molecular characteristics failed to predict response to cis/carboplatin and 5FU-based chemotherapy.

Challenging Knosp high-grade pituitary adenomas

2020 ◽  
Vol 132 (6) ◽  
pp. 1739-1746 ◽  
Author(s):  
Alexander Micko ◽  
Johannes Oberndorfer ◽  
Wolfgang J. Weninger ◽  
Greisa Vila ◽  
Romana Höftberger ◽  
...  
Keyword(s):  
Surgical Treatment ◽  
Carotid Artery ◽  
Pituitary Adenomas ◽  
Treatment Options ◽  
Cohort Analysis ◽  
Proliferation Rate ◽  
Biological Behavior ◽  
Complication Rates ◽  
High Grade ◽  
Significant Difference

OBJECTIVEParasellar growth is one of the most important prognostic variables of pituitary adenoma surgery, with adenomas regarded as not completely resectable if they invade the cavernous sinus (CS) but potentially curable if they displace CS structures. This study was conducted to correlate surgical treatment options and outcomes to the different biological behaviors (invasion vs displacement) of adenomas with parasellar extension into the superior or inferior CS compartments or completely encasing the carotid artery (Knosp high grades 3A, 3B, and 4).METHODSThis was a retrospective cohort analysis of 106 consecutive patients with Knosp high-grade pituitary adenomas with parasellar extension who underwent surgery via a primary endoscopic transsphenoidal approach between 2003 and 2017. Biological tumor characteristics (surgical status of invasiveness and tumor texture, 2017 WHO classification, proliferation rate), extent of resection, and complication rate were correlated with parasellar extension grades 3A, 3B, and 4 on preoperative MRI studies.RESULTSInvasiveness was significantly less common in grade 3A (44%) than in grade 3B (72%, p = 0.037) and grade 4 (100%, p < 0.001) adenomas. Fibrous tumor texture was significantly more common in grade 4 (52%) compared to grade 3A (20%, p = 0.002), but not compared to grade 3B (28%) adenomas. Functioning macroadenomas had a significantly higher rate of invasiveness than nonfunctioning adenomas (91% vs 55%, p = 0.002). Mean proliferation rate assessed by MIB-1 was > 3% in all groups but without significant difference between the groups (grade 3A, 3.2%; 3B, 3.9%; 4, 3.7%). Rates of endocrine remission/gross-total resection were significantly higher in grade 3A (64%) than in grade 3B (33%, p = 0.021) and grade 4 (0%, p < 0.001) adenomas. In terms of complication rates, no significant difference was observed between grades.CONCLUSIONSAccording to the authors’ data, the biological behavior of pituitary adenomas varies significantly between parasellar extension patterns. Adenomas with extension into the superior CS compartment have a lower rate of invasive growth than adenomas extending into the inferior CS compartment or encasing the carotid artery. Consequently, a significantly higher rate of remission can be achieved in grade 3A than in grade 3B and grade 4 adenomas. Therefore, the distinction into grades 3A, 3B, and 4 is of importance for prediction of adenoma invasion and surgical treatment considerations.

The Molecular Pathology of Eye Tumors: A 2019 Update Main Interests for Routine Clinical Practice

2019 ◽  
Vol 19 (9) ◽  
pp. 632-664
Author(s):  
Sacha Nahon-Esteve ◽  
Arnaud Martel ◽  
Célia Maschi ◽  
Jean-Pierre Caujolle ◽  
Stéphanie Baillif ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Molecular Pathology ◽  
Biological Diversity ◽  
Locally Advanced ◽  
Molecular Classification ◽  
Molecular Data ◽  
Molecular Alterations ◽  
Molecular Tests ◽  
Advanced Tumor ◽  
Therapeutic Decisions

Over the last few years, we have seen constant development of molecular pathology for the care of patients with cancer. The information obtained from molecular data has transformed our thinking about the biological diversity of cancers, particularly in the field of ophthalmic oncology. It has reoriented the way in which therapeutic decisions and decisions concerning patient surveillance are made, both in the area of pediatric cancers, including rhabdomyosarcoma and retinoblastoma, and adult cancers, such as uveal melanoma and lymphomas. A better definition of the molecular classification of these cancers and of the different biological pathways involved is essential to the understanding of both the pathologist and the onco-ophthalmologist. Molecular tests based on targeted or expanded analysis of gene panels are now available. These tests can be performed with tumor tissue or biofluids (especially blood) to predict the prognosis of tumors and, above all, the benefit of targeted therapies, immunotherapy or even chemotherapy. Looking for the BAP1 mutation in uveal melanoma is essential because of the associated metastatic risk. When treating retinoblastoma, it is mandatory to assess the heritable status of RB1. Conjunctival melanoma requires investigation into the BRAF mutation in the case of a locally advanced tumor. The understanding of genomic alterations, the results of molecular tests and/or other biological tests predictive of a therapeutic response, but also of the limits of these tests with respect to the available biological resources, represents a major challenge for optimal patient management in ophthalmic oncology. In this review, we present the current state of knowledge concerning the different molecular alterations and therapeutic targets of interest in ophthalmic oncology.

An overview of SELECTTION: Survey of European lung cancer evaluating choice of treatment and tolerability in observed second-line non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18204-18204
Author(s):  
E. F. Smit ◽  
A. Vergnenegre ◽  
J. Arellano ◽  
K. Kraaij ◽  
A. Kral ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Treatment Options ◽  
Locally Advanced ◽  
Real Life ◽  
Primary Objective ◽  
Treatment Discontinuation ◽  
Line Treatment ◽  
Second Line ◽  
Significant Difference ◽  
Choice Of Treatment

18204 Background: In addition to established second-line treatments for NSCLC in Europe, docetaxel and pemetrexed; erlotinib, has recently been approved. The only study directly comparing alternative options in second-line NSCLC showed no significant difference in efficacy between docetaxel and pemetrexed (median survival 7.9 vs 8.3 months, p = 0.226) but significant differences in toxicity profile (Hanna et al, 2004). It is of interest to observe how different second-line treatment options are used in real life settings, particularly length of therapy, reasons for discontinuation and its impact on patient’s outcomes. Methods: In observational studies patients are not assigned to different treatments at random and physicians and patients decide on treatment. A careful design is paramount to ensure the correct interpretation of data obtained. SELECTTION is the first observational, non-interventional, prospective study to be carried out in Europe in second-line NSCLC treatment. The primary objective of SELECTTION is to assess the time from treatment initiation to treatment discontinuation. Secondary objectives are to observe the reasons for treatment discontinuation and assess its impact on patient’s outcomes. A total of 13 countries will participate including: France, Portugal, Germany, Denmark, and UK with approximately 200 sites enrolling 950 patients. Information regarding patients and disease characteristics and treatment history are collected. Patients may be enrolled if they have received first-line chemotherapy for locally advanced or metastatic NSCLC, and have subsequently progressed, are at least 18 years old and are about to initiate second line treatment. Treatment cohorts will be constructed based on the distribution of patients across second-line treatments by physician decision. Results: At this stage details about design and analyses planned as well as evolution of the study, will be presented. Conclusions: SELECTTION will provide a unique set of data on how patients with stage IIIb\/IV NSCLC previously treated with chemotherapy, are treated in routine clinical practice. No significant financial relationships to disclose.

scholarly journals Anatomic locations in high grade glioma

2015 ◽  
Vol 29 (3) ◽  
pp. 271-277
Author(s):  
A. Oslobanu ◽  
St.I. Florian
Keyword(s):  
Frontal Lobe ◽  
Therapeutic Strategy ◽  
Parietal Lobe ◽  
Treatment Options ◽  
High Grade Glioma ◽  
Anatomical Location ◽  
High Grade ◽  
Significant Difference ◽  
Anatomic Locations ◽  
The Right

Abstract The treatment options and prognosis in gliomas could be determined by anatomic topographic location, beside different subtypes of glioma. The aim of this study is to find if any correlation between anatomical location of a glioma and the different subtypes of high grade glioma exist, and if this differences exists, does this influence the treatment options in terms of surgery. To do this, a representative group of 318 adults with high grade glioma was used. The most frequent subtypes of high grade glioma were glioblastoma (76,1%) followed by anaplastic astrocytomas (19,1%), anaplastic oligodendrogliomas (2,2), anaplastic ependymomas (1,2%), anaplastic oligoastrocytomas (0,9%), and anaplastic oligoastrocyomas (0,3%). The most frequent locations of gliomas were in the right frontal lobe in 11,95% of the cases, followed by left frontal in 9,12%, left temporal in 9,12%, right parietal in 8,18%, left parietal in 6,60%, right temporal in 5,66% for one lobe location. For multiple lobe locations the left fronto-parietal and left temporo-parietal (5,03%) were the most frequent locations. Deep-seated locations were present in 1,56% of the cases, and brain stem location was in 3,46%. No significant difference was observed between left or right predominence. Regarding the results among different subtypes of high grade glioma we noted that the anaplastic astrocytomas were more frequently located at the right frontal lobe in 18,03% compare to left frontal and left parietal lobe in 9,83%. In glioblastoma we found no significant differences in anatomical location as seen in anaplastic astrocytomas. These data results from our study could affect the therapeutic strategy regarding the extent of tumors resection.

scholarly journals High Grade Meningiomas: Current Therapy Based on Tumor Biology

2021 ◽  
Author(s):  
Juan Esteban Garcia-Robledo ◽  
Camila Ordóñez-Reyes ◽  
Alejandro Ruiz-Patiño ◽  
Álvaro Muñoz ◽  
Oscar Arrieta ◽  
...  
Keyword(s):  
Drug Targets ◽  
Treatment Options ◽  
Tumor Biology ◽  
Molecular Therapy ◽  
Current Therapy ◽  
High Recurrence Rate ◽  
High Grade ◽  
Who Grade ◽  
Emerging Treatments ◽  
Molecular Sequencing

Atypical (WHO grade II) and malignant meningiomas (WHO Grade III) are a rare subset of primary intracranial tumors. Due to the high recurrence rate after surgical resection and radiotherapy, there has been a recent interest in exploring other systemic treatment options for these refractory tumors. Recent advances in molecular sequencing of tumors have elucidated new pathways and drug targets currently being studied. This article provides a thorough overview of novel investigational therapeutics, including targeted therapy, immunotherapy, and new technological modalities for atypical and malignant meningiomas. There is encouraging preclinical evidence regarding the efficacy of the emerging treatments discussed in this chapter. Several clinical trials are currently recruiting patients to translate targeted molecular therapy for recurrent and high-grade meningiomas.

scholarly journals Evaluation of PARP and PDL-1 as potential therapeutic targets for women with high-grade neuroendocrine carcinomas of the cervix

2020 ◽  
Vol 30 (9) ◽  
pp. 1303-1307 ◽  
Author(s):  
Matthew Ryan Carroll ◽  
Preetha Ramalingam ◽  
Gloria Salvo ◽  
Junya Fujimoto ◽  
Luisa Maren Solis Soto ◽  
...  
Keyword(s):  
Mismatch Repair ◽  
Treatment Options ◽  
Therapeutic Targets ◽  
Large Cell ◽  
Small Cell ◽  
Cancer Center ◽  
High Grade ◽  
Mismatch Repair Proteins ◽  
Parp 1 ◽  
Neuroendocrine Carcinomas

ObjectivesWomen with recurrent high-grade neuroendocrine cervical cancer have few effective treatment options. The aim of this study was to identify potential therapeutic targets for women with this disease.MethodsSpecimens from patients with high-grade neuroendocrine carcinomas of the cervix were identified from pathology files at MD Anderson Cancer Center. Immunohistochemical stains for PD-L1 (DAKO, clone 22-C3), mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), somatostatin, and Poly (ADP-ribose) polymerase (PARP) were performed on sections from formalin-fixed paraffin-embedded tissue blocks. Nuclear PARP-1 staining was quantified using the H-score with a score of <40 considered low, 40–100 moderate, and ≥100 high.ResultsForty pathologic specimens from patients with high-grade neuroendocrine carcinomas of the cervix were examined (23 small cell, 5 large cell, 3 high-grade neuroendocrine, not otherwise specified, and 9 mixed). The mean age of the cohort was 43 years and the majority of patients (70%) were identified as white non-Hispanic. All 28 (100%) samples tested stained for mismatch repair proteins demonstrated intact expression, suggesting they were microsatellite stable tumors. Of the 31 samples tested for PD-L1 expression, only two (8%) of the 25 pure high-grade neuroendocrine carcinomas were positive whereas three (50%) of the six mixed carcinoma tumors tested positive. Of the 11 small cell specimens tested for PARP-1, 10 (91%) showed PARP expression with six (55%) demonstrating high expression and four (36%) showing moderate expression. Somatostatin staining was negative in 18 of 19 small cell cases (95%).ConclusionsPure high-grade neuroendocrine cervical carcinomas were microsatellite stable and overwhelmingly negative for PD-L1 expression. As the majority of tumors tested expressed PARP-1, inclusion of PARP inhibitors in future clinical trials may be considered.

scholarly journals Genomic Heterogeneity of Breast Tumor Pathogenesis

2009 ◽  
Vol 3 ◽  
pp. CMO.S2946
Author(s):  
Rachel E. Ellsworth ◽  
Jeffrey A. Hooke ◽  
Craig D. Shriver ◽  
Darrell L. Ellsworth
Keyword(s):  
Current System ◽  
Treatment Options ◽  
Expression Patterns ◽  
Tumor Grade ◽  
Molecular Data ◽  
Clinical Test ◽  
Low Grade ◽  
High Grade ◽  
Breast Cancer Patients ◽  
Intermediate Grade

Pathological grade is a useful prognostic factor for stratifying breast cancer patients into favorable (low-grade, well-differentiated tumors) and less favorable (high-grade, poorly-differentiated tumors) outcome groups. Under the current system of tumor grading, however, a large proportion of tumors are characterized as intermediate-grade, making determination of optimal treatments difficult. In an effort to increase objectivity in the pathological assessment of tumor grade, differences in chromosomal alterations and gene expression patterns have been characterized in low-grade, intermediate-grade, and high-grade disease. In this review, we outline molecular data supporting a linear model of progression from low-grade to high-grade carcinomas, as well as contradicting genetic data suggesting that low-grade and high-grade tumors develop independently. While debate regarding specific pathways of development continues, molecular data suggest that intermediate-grade tumors do not comprise an independent disease subtype, but represent clinical and molecular hybrids between low-grade and high-grade tumors. Finally, we discuss the clinical implications associated with different pathways of development, including a new clinical test to assign grade and guide treatment options.

scholarly journals Impact of a Molecular Sequencing Systematic at Diagnosis in Digestive Oncology: Experience of a French Center

2021 ◽  
pp. 1-13
Author(s):  
Bernadette de Rauglaudre ◽  
Bernadette de Rauglaudre ◽  
Emmanuelle Norguet-Monnereau ◽  
Muriel Duluc ◽  
Isabelle Nanni ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Throughput ◽  
Survival Data ◽  
Median Overall Survival ◽  
Disease Diagnosis ◽  
Digestive Cancer ◽  
Molecular Alterations ◽  
Significant Difference ◽  
Molecular Sequencing ◽  
Digestive Oncology

Introduction: Tumor-based molecular profiling has increased in the area of precision medicine. Their routine use is still limited by accessibility, cost and availability of tumor material. Materials and Methods: We retrospectively analysed the treatment received and the survival data of patients with digestive cancer who received molecular high-throughput sequencing (NGS) analyses at diagnosis. The primary objective of this single-center study was to compare the overall survival of patients who were treated with molecularly matched therapy with patients who received standard therapy. Median overall survival was calculated from initial disease diagnosis to death. Results: 528 patients were referred to the Digestive Oncology Department of the Timone Hospital in Marseille between January 2018, and November 2020 for management of digestive cancer and received high-throughput molecular sequencing. Among them, 461 patients had a digestive carcinoma (75 of them were excluded because of the presence of a GIST or a neuroendocrine tumor, a digestive localization of extra digestive cancer or the absence of follow-up in our center) and 275 had metastatic disease (synchronous or metachronous). For metastatic patients, actionable molecular alterations were identified in95 patients (43.5%) and for 13 patients (4.7%) a molecularly matched therapy was administered. There was no significant difference in median overall survival between patients who received matched therapy than patients who did not receive molecularly matched therapy (2.89 [95%CI 1.84 - 3.93] vs. 2.86 [95%CI 1.52 - 4.19], p=0.671). Conclusion: This study suggests that high-throughput genomics can improve management of patients. Although these results did not show a benefit in overall survival for tumors who harboured such actionable molecular alterations and who received molecularly matched therapy, than patients who did not receive molecularly matched therapy, they are promising. Randomized trials are needed to confirm that there is a benefit to treating patients with matched therapy based on NGS.

scholarly journals Hemispherical Pediatric High-Grade Glioma: Molecular Basis and Therapeutic Opportunities

2020 ◽  
Vol 21 (24) ◽  
pp. 9654
Author(s):  
Santiago Haase ◽  
Fernando M. Nuñez ◽  
Jessica C. Gauss ◽  
Sarah Thompson ◽  
Emily Brumley ◽  
...  
Keyword(s):  
Cell Biology ◽  
High Grade Glioma ◽  
Cerebral Hemispheres ◽  
Clinical State ◽  
Molecular Characteristics ◽  
High Grade ◽  
Molecular Alterations ◽  
Current Therapies ◽  
Pediatric High Grade Glioma

In this review, we discuss the molecular characteristics, development, evolution, and therapeutic perspectives for pediatric high-grade glioma (pHGG) arising in cerebral hemispheres. Recently, the understanding of biology of pHGG experienced a revolution with discoveries arising from genomic and epigenomic high-throughput profiling techniques. These findings led to identification of prevalent molecular alterations in pHGG and revealed a strong connection between epigenetic dysregulation and pHGG development. Although we are only beginning to unravel the molecular biology underlying pHGG, there is a desperate need to develop therapies that would improve the outcome of pHGG patients, as current therapies do not elicit significant improvement in median survival for this patient population. We explore the molecular and cell biology and clinical state-of-the-art of pediatric high-grade gliomas (pHGGs) arising in cerebral hemispheres. We discuss the role of driving mutations, with a special consideration of the role of epigenetic-disrupting mutations. We will also discuss the possibilities of targeting unique molecular vulnerabilities of hemispherical pHGG to design innovative tailored therapies.

Long-term survival of the nasal NK/T cell lymphoma

2008 ◽  
Vol 149 (17) ◽  
pp. 801-805
Author(s):  
Péter Rajnics ◽  
László Krenács ◽  
András Kenéz ◽  
Zoltán Járay ◽  
Enikő Bagdi ◽  
...  
Keyword(s):  
T Cell ◽  
Treatment Guidelines ◽  
Cell Lymphoma ◽  
Treatment Options ◽  
Diagnostic Procedures ◽  
T Cell Lymphoma ◽  
Term Survival ◽  
Barr Virus ◽  
Significant Difference ◽  
Nk T Cell

The nasal NK/T cell lymphoma is a rare, extranodal non-Hodgkin lymphoma in western civilizations, which has poor prognosis. The Epstein–Barr virus can be detected in tumor cells in nearly all cases. There are no definite treatment guidelines in our days. There is no significant difference in survival between radiotherapy and chemotherapy according to Asian studies. In this case study we show our diagnostic procedures, our treatment options and we present the summary of this illness based on the data found in the literature.

Sign in / Sign up

Export Citation Format

Share Document