Considerations concerning a tailored, individualized therapeutic management of patients with (neuro)endocrine tumours of the gastrointestinal tract and pancreas.

2004 ◽  
Vol 11 (1) ◽  
pp. 19-34 ◽  
Author(s):  
W W de Herder ◽  
E P Krenning ◽  
C H J Van Eijck ◽  
S W J Lamberts
Keyword(s):  
Gastrointestinal Tract ◽  
Somatostatin Analogues ◽  
Team Approach ◽  
First Line ◽  
Endocrine Tumours ◽  
First Line Therapy ◽  
Hereditary Syndromes ◽  
Localized Disease ◽  
Disease Stages

Endocrine tumours of the gastrointestinal tract and pancreas may present at different disease stages with either hormonal or hormone-related symptoms/syndromes, or without hormonal symptoms. They may occur either sporadically or as part of hereditary syndromes. In the therapeutic approach to a patient with these tumours, excessive hormonal secretion and/or its effects should always be controlled first. Tumour-related deficiencies or disorders should also be corrected. Subsequently, control should be aimed at the tumour growth. Surgery is generally considered as first-line therapy for patients with localized disease, as it can be curative. However, in patients with metastatic disease the role of first-line surgery is not clearly established and other therapies should be considered, such as non-surgical cytoreductive therapies, biotherapy (with somatostatin analogues or interferon-alpha), embolization and chemoembolization of liver metastases, chemotherapy (with single or multiple dose regimens) and peptide receptor-targeted radiotherapy. The delicate balance of the use of the different therapeutical options in patients with endocrine tumours of the gastrointestinal tract and pancreas emphasizes the importance of team approach and team expertise.

scholarly journals Practical Aspects of Interface Application in CPAP Treatment

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Adel Bachour ◽  
Heidi Avellan-Hietanen ◽  
Tuula Palotie ◽  
Paula Virkkula
Keyword(s):  
Airway Pressure ◽  
Positive Airway Pressure ◽  
Medical Team ◽  
Cpap Therapy ◽  
Air Leak ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Nasal Stuffiness

While continuous positive airway pressure (CPAP) is an effective first-line therapy for sleep apnea, CPAP fails in one third of patients mainly due to poor adherence to the CPAP device and masks. The role of the medical team is to guide the patient in choosing the best mask, thus insuring good CPAP therapy adherence. Once a suitable mask is found, the brand of the mask does not affect patient satisfaction or CPAP adherence. For the majority of patients, nasal masks are by far more suitable than oronasal masks. Orosanal masks are indicated in case of nasal stuffiness or when an air leak manifests through the mouth. Re-evaluation of the efficacy of CPAP therapy is recommended when switching to oronasal masks.

Reversal of Resistance to Doxifluridine and Fluorouracil in Metastatic Colorectal Cancer: The Role of High-Dose Folinic Acid

1992 ◽  
Vol 78 (4) ◽  
pp. 258-261 ◽  
Author(s):  
Marco Colleoni ◽  
Emilio Bajetta ◽  
Filippo de Braud ◽  
Nicoletta Zilembo ◽  
Franco Noiè ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Folinic Acid ◽  
Performance Status ◽  
Objective Response ◽  
High Dose ◽  
Severe Toxicity ◽  
First Line ◽  
First Line Therapy ◽  
Colon And Rectum

The benefits from medical treatment in colorectal cancer are limited. Fluorouracil remains the only recognized drug, and how to treat unresponsive patients is still debated. To evaluate the role of folinic acid (FA) in circumvence resistance in colorectal cancer, 28 patients pretreated with fluoropyrimidine were candidated to receive one of the following schedules: fluorouracil (600 mg/m2) associated with FA (500 mg/m2) weekly for 6 weeks (Regimen A: 21 cases), or fluorouracil (370 mg/m2) plus FA (200 mg/m2) dally for 5 days every 4 weeks (Regimen B: 7 cases). Fourteen patients were pretreated with doxifluridlne, a new fluoropyrimldine derivative with a peculiar mechanism of action, and the remaining 14 patients with fluorouracil. All but 2 patients were unresponsive to first-line treatments. When the treatment began, the median age of the patients was 60 years (range, 30-68). The performance status (ECOG) was 0/1 in 25 of them, and the primary tumor was in the colon and rectum in 19 and 9 patients, respectively. Sites of disease were liver (64 %), lung (35 %), local recurrence (10 %) and peritoneum (10 %). A median of 3 cycles (range, 1-7) was delivered, and no objective response was observed in the group of patients pretreated with doxlfluridine or in the group pretreated with fluorouracil. In 5 cases a significant decrease in baseline CEA values was observed. Therapy was well tolerated, and no grade 4 toxicity was encountered. Severe toxicity was limited and included diarrhea (7 patients), stomatitis (1 patient) and nausea/vomiting (1 patient). High-dose FA has no role in reversing resistance to fluoropyrimidine, and other mechanisms of refractoriness are surely involved. FA should be associated with fluoropyrimidine as first-line therapy together with other biochemical modulators. Further rescue therapies need to be developed.

scholarly journals Endovascular management of spinal vascular malformations: history and literature review

2009 ◽  
Vol 26 (1) ◽  
pp. E7 ◽  
Author(s):  
Ricky Medel ◽  
R. Webster Crowley ◽  
Aaron S. Dumont
Keyword(s):  
Endovascular Therapy ◽  
Surgical Intervention ◽  
Vascular Malformations ◽  
Therapeutic Tool ◽  
First Line ◽  
Spinal Vascular Malformations ◽  
First Line Therapy ◽  
Treatment Paradigm ◽  
The 1960S

Spinal vascular malformations represent a complex group of entities whose treatment paradigm continually evolves. Given the ever-increasing role of endovascular therapy, it is the goal of the authors to review the current literature regarding this therapeutic tool and to provide recommendations guiding management. A thorough literature search was conducted using Medline, with subsequent articles being identified through cross-referencing. The analysis revealed that, since its introduction in the 1960s, endovascular therapy has been used to manage the entire spectrum of spinal vascular malformations, during which period it has undergone considerable technological and technical evolution. As such, embolization has proved of growing therapeutic utility, largely resulting from the mounting evidence supporting its safety and efficacy, in addition to the inherent minimally invasive nature. This alternative to surgical intervention will be increasingly used as first-line therapy in spinal vascular malformations.

KIT and PDGFRAmutation status and their immunohistochemical (IHC) expression profile of gastrointestinal stromal tumor (GIST) patients treated with imatinib (IMT): Seven-year single-center experience

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 10558-10558
Author(s):  
Y. Koh ◽  
H. Kim ◽  
H. Lee ◽  
K. Lee ◽  
D. Oh ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
First Line ◽  
Mutation Status ◽  
Single Center Experience ◽  
First Line Therapy ◽  
Positive Rate ◽  
Exon 11 ◽  
Tumor Dna

10558 Background: Previous studies suggested the role of KIT and PDGFRAmutations on treatment outcome of GIST with IMT, but results are heterogeneous. IHC value of PDGFRA and PDGFRB is not established. Methods: We included patients (pts) treated with IMT as a first line therapy for metastastic or relapsed GIST between 2001 and 2008. Tumor DNA was extracted to investigate the mutation status of KITexon 9, exon 11, PDGFRA exon 12 and 18. IHC stain of c-KIT and PDGFRA/B was performed. We assessed the correlation between the treatment outcome, genetic status and IHC results. Results: A total of 85 pts (M:F=49:36, median age 58.4 years) received IMT 400 mg daily. Location of primary disease included stomach (33), small bowel (34), rectum (10), esophagus (1), and omentum/mesentery (7). Complete and partial responses were achieved in 6% and 62% of pts respectively, while 5% of pts had progressive disease. During median follow up of 28.1 months, estimated median PFS was 39.8 months. KIT exon 11 and 9 mutations were detected in 64% and 5% respectively. Exon 11 mutations included 44 deletions, 2 insertions, 5 substitutions and 3 deletion/insertions. PDGFRA exon 12 and 18 mutations were detected in 2% respectively. Positive rate of c-KIT, PDGFRA and PDGFRB using IHC was 96%, 21%, and 26% respectively. PDGFRA and PDGFRB were co-expressed (p=0.001). PDGFRA mutation did not correlate with PDGFRA/B expression. Clinical response was not different according to the mutation status or IHC expression. PFS of KIT exon 11, KITexon 9, PDGFRA mutants and pts without detectable mutations were not different (p=0.397). Pts with KIT exon 11 balanced mutations (substitution or deletion/insertion) showed longer PFS compared with pts with unbalanced mutations (deletion or insertion) (p=0.014) or pts without exon 11 mutations (p=0.033). Median PFS was shorter in pts lacking c-KIT (p=0.001) expression. PDGFRA/B expression did not influence PFS. Conclusions: Balanced mutation of KIT exon 11 predicted longer PFS, while lack of c-KIT protein expression predicted shorter PFS for GIST pts treated with first line IMT. PDGFRA and B were co-expressed without predictive value. No significant financial relationships to disclose.

Treatment patterns of gastrointestinal neuroendocrine tumors (NET).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 387-387
Author(s):  
Michael S. Broder ◽  
Eunice Chang ◽  
Beilei Cai ◽  
Maureen Neary ◽  
Elya Papoyan ◽  
...  
Keyword(s):  
Disease Status ◽  
Somatostatin Analogues ◽  
Pharmacological Therapy ◽  
Treatment Patterns ◽  
Second Line ◽  
First Line ◽  
Nccn Guidelines ◽  
First Line Therapy ◽  
Line Therapy ◽  
New Treatments

387 Background: NET comprise a broad set of rare tumors. Almost 2/3 arise in the gastrointestinal (GI) tract. NCCN guidelines for unresectable GI NET recommend somatostatin analogues (SSA) first, however, guidelines do not recommend a particular sequence for remaining therapies. Our objective is to describe real world treatment patterns of GI NET. Methods: This retrospective study combined 2 claims databases to examine newly pharmacologically treated patients using tabular and graphical techniques. Treatments included SSA, cytotoxic chemotherapy (CC), targeted therapy (TT), interferon (IF) and combinations. Patients ≥ 18 years, with ≥ 1 inpatient or ≥ 2 outpatient claims for GI NET who received pharmacologic treatment from 7/1/09-6/30/14 were identified. A 6 month clean period prior to first treatment ensured patients were newly treated. Patients were followed until end of enrollment. Results: We identified 2,258 newly treated GI NET patients. 59.6% started first line therapy with SSA monotherapy, 33.3% CC, 3.6% TT, and 0.5% IF. The remainder received combination therapies. Mean follow up was 576 days. Mean duration of first line therapy was 361 days for all newly treated patients (449 SSA, 215 CC, 267 TT). 58.9% of patients had no subsequent pharmarcological treatment after discontinuation of first line therapy.The most common second line was combination therapy with SSA (i.e., CC or TT added). In patients who did not begin with SSA, most received SSA as second line. In graphical pattern analysis, there was no clear pattern visible after first line therapy. Conclusions: More than 1/2 of pharmacologically treated patients began treatment with SSA and 1/3 with CC, with duration of use > 1 year and just over 6 months, respectively. We found treatment patterns after first line were unclear, and more than 1/2 of patients had no subsequent pharmacological treatments after discontinuing first line therapy. It is unclear whether there is underutilization of the pharmacological therapy or this is due to stable disease status after alternative non-pharmacological treatment. Future studies directed at understanding treatment patterns using patient medical records are warranted. As new treatments emerge, reassessment of treatment patterns may be needed.

Progression-free survival in patients with cholangiocarcinoma with FGFR2 fusions or rearrangements: An exploration of response to systemic therapy.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 588-588 ◽  
Author(s):  
Kristen Bibeau ◽  
Luis Féliz ◽  
Scott Barrett ◽  
Ling Na ◽  
Christine Francis Lihou ◽  
...  
Keyword(s):  
Systemic Therapy ◽  
Progression Free Survival ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Free Survival ◽  
Prior Therapy ◽  
First Line Therapy ◽  
Line Therapy

588 Background: Most cholangiocarcinoma (CCA) patients (pts) are diagnosed with advanced disease and are ineligible for surgery. FGFR2 fusions or rearrangements are present in 10–16% of pts with intrahepatic CCA (iCCA) and are reported to be oncogenic drivers. However, little data are available on the role of FGFR2 genetic alterations in the response to systemic cancer therapy. FIGHT-202 is a phase 2 study of pemigatinib (a selective, potent, oral FGFR1–3 inhibitor) in pts with previously treated advanced/metastatic CCA (NCT02924376); primary results were reported at ESMO 2019. FIGHT-202 enrolled pts who progressed on ≥1 prior therapy, allowing the examination of the role of FGFR2 alterations on the response to prior therapy. The objective of this post hoc analysis was to evaluate progression free survival (PFS) on standard systemic therapy received prior to study enrollment among pts with CCA harboring FGFR2 fusions or rearrangements ( FGFR2+). Methods: Case report forms were reviewed to determine disease history and exposure to prior lines of systemic cancer therapies (LOSCT) in the advanced setting before receiving pemigatinib. Only pts with sufficient data on prior LOSCT were included in this analysis. Median PFS was calculated using the Kaplan-Meier method. Results: 102 pts were included in this analysis (median age 54.5, 61.8% female). Median PFS on first-line therapy was 5.5 (95% CI: 4.0, 8.0) months. Among the 38 pts (37.3%) with ≥2 prior LOSCT, median PFS on second-line therapy was 4.4 (95% CI: 3.0, 5.3) months. Conclusions: This analysis provides data about PFS on standard systemic therapies for pts with FGFR2+ CCA. Median PFS on first-line therapy was lower than historical published data, and median PFS on second-line therapy was slightly longer than previously reported, in unselected CCA populations. Limitations of this analysis include retrospective examination of investigator reported data, and that clinical trial participants may not truly reflect a general CCA patient population. The short PFS on standard therapies in pts with FGFR2+ CCA highlights the need for development of other options including targeted therapies to improve outcomes.

scholarly journals Multifactorial Role of Mitochondria in Echinocandin Tolerance Revealed by Transcriptome Analysis of Drug-Tolerant Cells

mBio ◽  
2021 ◽  
Author(s):  
Rocio Garcia-Rubio ◽  
Cristina Jimenez-Ortigosa ◽  
Lucius DeGregorio ◽  
Christopher Quinteros ◽  
Erika Shor ◽  
...  
Keyword(s):  
Fungal Pathogen ◽  
Candida Glabrata ◽  
Clinical Failure ◽  
First Line ◽  
Content Type ◽  
First Line Therapy ◽  
Line Therapy ◽  
Resistant Strains ◽  
Opportunistic Fungal Pathogen

Echinocandin drugs are a first-line therapy to treat invasive candidiasis, which is a major source of morbidity and mortality worldwide. The opportunistic fungal pathogen Candida glabrata is a prominent bloodstream fungal pathogen, and it is notable for rapidly developing echinocandin-resistant strains associated with clinical failure.

scholarly journals The role of rituximab in adults with warm antibody autoimmune hemolytic anemia

Blood ◽  
2015 ◽  
Vol 125 (21) ◽  
pp. 3223-3229 ◽  
Author(s):  
Daan Dierickx ◽  
Alain Kentos ◽  
André Delannoy
Keyword(s):  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Randomized Study ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
First Line Therapy ◽  
Line Therapy

Abstract Warm antibody hemolytic anemia is the most common form of autoimmune hemolytic anemia. When therapy is needed, corticosteroids remain the cornerstone of initial treatment but are able to cure only a minority of patients (<20%). Splenectomy is usually proposed when a second-line therapy is needed. This classical approach is now challenged by the use of rituximab both as second-line and as first-line therapy. Second-line treatment with rituximab leads to response rates similar to splenectomy (∼70%), but rituximab-induced responses seem less sustained. However, additional courses of rituximab are most often followed by responses, at the price of reasonable toxicity. In some major European centers, rituximab is now the preferred second-line therapy of warm antibody hemolytic anemia in adults, although no prospective study convincingly supports this attitude. A recent randomized study strongly suggests that in first-line treatment, rituximab combined with steroids is superior to monotherapy with steroids. If this finding is confirmed, rituximab will emerge as a major component of the management of warm antibody hemolytic anemia not only after relapse but as soon as treatment is needed.

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