scholarly journals Identification and overcoming of resistance to somatostatin analogues in real clinical practice

2017 ◽  
Vol 63 (5) ◽  
pp. 338-345
Author(s):  
Irena A. Ilovayskaya
Keyword(s):  
Clinical Practice ◽  
First Generation ◽  
Tumor Response ◽  
Treatment Options ◽  
Combined Treatment ◽  
Somatostatin Analogues ◽  
Response To Treatment ◽  
Ki 67 ◽  
Genetic Predictors ◽  
Personalized Approach

Resistance to somatostatin analogues (SSAs) is defined as the lack of biochemical and tumor response to the treatment for 12 months. An adequate biochemical response means achieving the target criteria of acromegaly treatment or at least a decrease in the GH and/or IGF-1 levels by >50%. A decrease in the somatotropinoma size by ≥ 20% (when using SSAs as the first line treatment) is considered as the tumor response to treatment. On the basis of treatment efficacy, patients may be classified as non-resistant (biochemical control of acromegaly and tumor response), partially resistant (some degree of biochemical and/or tumor response), and fully resistant (neither biochemical nor tumor response) to SSA therapy. Most patients (up to 60—70%) are partially resistant to the first generation of SSAs. Clinical and biochemical predictors for resistance to SSAs include young age, male gender, high GH/IGF-1 levels, and large invasive sparsely granulated somatotropinoma with high Ki-67 and a hyperintense T2-weighted MRI signal. In recent years, various molecular and genetic predictors for resistance to SSAs have been found; they should be introduced in clinical practice to enable the personalized approach to drug therapy. Treatment options for patients resistant to first-generation SSAs include dose escalation, combined treatment with SSAs and cabergoline, and switching to pasireotide or pegvisomant (not available in Russia); non-drug options include tumor debulking followed by SSA therapy and radiosurgery/radiotherapy.

Target therapies plus somatostatin analogues in NETs: a network meta-analysis

2021 ◽  
Author(s):  
Sara Pusceddu ◽  
Antonio Facciorusso ◽  
Luca Giacomelli ◽  
Natalie Prinzi ◽  
Francesca Corti ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Combination Therapy ◽  
Meta Analysis ◽  
Treatment Options ◽  
Combined Treatment ◽  
Secondary Analysis ◽  
Treatment Strategies ◽  
Progression Free Survival ◽  
Somatostatin Analogues

Although combination therapy is not recommended in patients with gastro-entero-pancreatic (GEP) neuroendocrine tumors (NETs), this strategy is widely used in clinical practice. This network meta-analysis of randomized trials evaluates targeted therapies and somatostatin analogues in GEP advanced NETs, either alone or in combination, comparing the efficacy of different single or combined treatment strategies in terms of progression-free survival (PFS). Interventions were grouped as analogues, everolimus, everolimus plus SSAs, sunitinib and placebo. In a secondary analysis, we also assessed the efficacy of individual specific pharmacological treatments versus placebo or each other. From 83 studies identified, 8 randomized controlled trials were selected, with a total of 1849 patients with either functioning or non-functioning NETs. The analysis confirmed the superiority of all treatments over placebo (HR ranging from 0.34, 95% CI: 0.24–0.37 with the combination of everolimus plus SSAs to 0.42, 0.31–0.57 with the analogues; moderate quality of evidence). On ranking analysis, the combination of everolimus plus SSA (P score=0.86) and then everolimus alone (P score=0.65) ranked highest in increasing PFS. On comparative evaluation of different interventions, pasireotide (P score=0.96) and everolimus+octreotide (P score=0.82) ranked as the best pharmacological treatment options. Our findings support the use of combination therapy in the treatment of functioning and non-functioning GEP NETs. The role of pasireotide should be explored in selected subgroups of patients. Last, the combination of everolimus and octreotide appears promising and should be more widely considered in clinical practice.

scholarly journals The role of the neoadjuvant approach in the treatment of primary operable HER2 positive breast cancer

2020 ◽  
Vol 10 (2) ◽  
pp. 45-52
Author(s):  
M. A. Frolova ◽  
Е. V. Glazkova ◽  
A. V. Petrovsky ◽  
О. V. Krokhina ◽  
M. В. Stenina ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Response ◽  
Residual Tumor ◽  
Response To Treatment ◽  
Comprehensive Treatment ◽  
Her2 Positive ◽  
Ki 67 ◽  
Her2 Positive Breast Cancer ◽  
Neoadjuvant Systemic Therapy ◽  
Positive Breast Cancer

Neoadjuvant systemic therapy is an essential component of the comprehensive treatment of primary operable HER2‑positive breast cancer. Therefore, it is extremely important to search for treatment efficacy predictors and optimal system for assessing tumor response to treatment. The study analyzed factors predicting pathological complete response (pCR) in patients with luminal and non‑luminal HER2‑positive tumor subtypes. The morphological assessment of the tumor response to treatment was carried out using the RCB system; additional characteristics of the residual tumor were studied as well. It was shown that a comprehensive assessment involving the use of the RCB system and determination of the Ki ‑ 67 level helps to divide patients into prognostic groups and individualize the adjuvant therapy plan.

scholarly journals Resistance to drug treatment of acromegaly and ways to overcome it

2021 ◽  
Vol 18 (2) ◽  
pp. 150-162
Author(s):  
O. O. Golounina ◽  
L. K. Dzeranova ◽  
E. A. Pigarova ◽  
Zh. E. Belaya
Keyword(s):  
Growth Hormone ◽  
Drug Treatment ◽  
Growth Hormone Receptor ◽  
First Generation ◽  
Treatment Method ◽  
Somatostatin Analogues ◽  
Biochemical Remission ◽  
High Doses ◽  
Personalized Approach ◽  
Selection Of

Acromegaly is a severe disabling neuroendocrine disease caused by hypersecretion of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). The problem of resistance to drug therapy in patients with acromegaly is quite common in clinical practice and requires a personalized approach, considering various predictors of sensitivity to the choice of the treatment method. To date, first-generation somatostatin analogues are first-line drugs in the medical treatment of acromegaly, but up to 50% of patients do not achieve biochemical remission of the disease. The prognosis of sensitivity to somatostatin analogues is of great importance and the selection of patients in whom this therapy will be not successful provides invaluable assistance in choosing the optimal treatment approach. This review summarizes potential predictors of sensitivity and resistance to existing drug treatment of acromegaly, discusses possible ways to overcome the resulting resistance to therapy, suggests options for a personalized approach to choosing a treatment strategy in the absence of disease control against the background of monotherapy with somatostatin analogues, including «off-label» combinations. Timely addition of growth hormone receptor antagonist (pegvisomant) avoids repeated neurosurgical intervention, radiation therapy or prescribing excessively high doses of somatostatin analogues. Optimal use of mono- or combination therapy contributes to the achievement of biochemical remission in most resistant patients.

scholarly journals European Psychiatric Association Guidance on psychotherapy in chronic depression across Europe

2016 ◽  
Vol 33 (1) ◽  
pp. 18-36 ◽  
Author(s):  
A. Jobst ◽  
E.-L. Brakemeier ◽  
A. Buchheim ◽  
F. Caspar ◽  
P. Cuijpers ◽  
...  
Keyword(s):  
Treatment Options ◽  
Combined Treatment ◽  
Treatment Algorithm ◽  
Chronic Depression ◽  
Comprehensive Overview ◽  
Psychotherapeutic Treatment ◽  
Cognitive Behavioural ◽  
Icd 10 ◽  
Personalized Approach ◽  
Analysis System

AbstractPurposePatients with chronic depression (CD) by definition respond less well to standard forms of psychotherapy and are more likely to be high utilizers of psychiatric resources. Therefore, the aim of this guidance paper is to provide a comprehensive overview of current psychotherapy for CD. The evidence of efficacy is critically reviewed and recommendations for clinical applications and research are given.MethodsWe performed a systematic literature search to identify studies on psychotherapy in CD, evaluated the retrieved documents and developed evidence tables and recommendations through a consensus process among experts and stakeholders.ResultsWe developed 5 recommendations which may help providers to select psychotherapeutic treatment options for this patient group. The EPA considers both psychotherapy and pharmacotherapy to be effective in CD and recommends both approaches. The best effect is achieved by combined treatment with psychotherapy and pharmacotherapy, which should therefore be the treatment of choice. The EPA recommends psychotherapy with an interpersonal focus (e.g. the Cognitive Behavioural Analysis System of Psychotherapy [CBASP]) for the treatment of CD and a personalized approach based on the patient's preferences.DiscussionThe DSM-5 nomenclature of persistent depressive disorder (PDD), which includes CD subtypes, has been an important step towards a more differentiated treatment and understanding of these complex affective disorders. Apart from dysthymia, ICD-10 still does not provide a separate entity for a chronic course of depression. The differences between patients with acute episodic depression and those with CD need to be considered in the planning of treatment. Specific psychotherapeutic treatment options are recommended for patients with CD.ConclusionPatients with chronic forms of depression should be offered tailored psychotherapeutic treatments that address their specific needs and deficits. Combination treatment with psychotherapy and pharmacotherapy is the first-line treatment recommended for CD. More research is needed to develop more effective treatments for CD, especially in the longer term, and to identify which patients benefit from which treatment algorithm.

scholarly journals Factors predicting pasireotide responsiveness in somatotroph pituitary adenomas resistant to first-generation somatostatin analogues: an immunohistochemical study

2016 ◽  
Vol 174 (2) ◽  
pp. 241-250 ◽  
Author(s):  
Donato Iacovazzo ◽  
Eivind Carlsen ◽  
Francesca Lugli ◽  
Sabrina Chiloiro ◽  
Serena Piacentini ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Scoring System ◽  
First Generation ◽  
Immunohistochemical Study ◽  
Somatostatin Analogues ◽  
Ki 67

AimTo gather data regarding factors predicting responsiveness to pasireotide in acromegaly.Patients and methodsSSTR2a, SSTR3, SSTR5, AIP, Ki-67 and the adenoma subtype were evaluated in somatotroph adenomas from 39 patients treated post-operatively with somatostatin analogues (SSAs). A standardized SSTR scoring system was applied (scores 0–3). All patients received first-generation SSAs, and 11 resistant patients were subsequently treated with pasireotide LAR.ResultsNone of the patients with negative or cytoplasmic-only SSTR2a expression (scores 0–1) were responsive to first-generation SSAs, as opposed to 20% (score 2) and 50% of patients with a score of 3 (P=0.04). None of the patients with an SSTR5 score of 0–1 were responsive to pasireotide, as opposed to 5/7 cases with a score of 2 or 3 (P=0.02). SSTR3 expression did not influence first-generation SSAs or pasireotide responsiveness. Tumours with low AIP were resistant to first-generation SSAs (100 vs 60%; P=0.02), while they had similar responsiveness to pasireotide compared to tumours with conserved AIP expression (50 vs 40%; P=0.74). Tumours with low AIP displayed reduced SSTR2 (SSTR2a scores 0–1 44.4 vs 6.7%; P=0.006) while no difference was seen in SSTR5 (SSTR5 scores 0–1 33.3 vs 23.3%; P=0.55). Sparsely granulated adenomas responded better to pasireotide compared to densely granulated ones (80 vs 16.7%; P=0.04).ConclusionThe expression of SSTR5 might predict responsiveness to pasireotide in acromegaly. AIP deficient and sparsely granulated adenomas may benefit from pasireotide treatment. These results need to be confirmed in larger series of pasireotide-treated patients.

Combined treatment for small cell lung cancer

2021 ◽  
pp. 30-48
Author(s):  
Aslan Alekseevich Teuvov ◽  
Arthur Mukharbievich Baziev ◽  
Aslan Zhamalovich Zhashuev ◽  
Zarema Nuridinovna Lovpache ◽  
Takhir Zhambotovich Glashev
Keyword(s):  
Lung Cancer ◽  
Clinical Practice ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Treatment Options ◽  
Combined Treatment ◽  
Small Cell ◽  
Therapeutic Approaches ◽  
Small Cell Lung ◽  
Made In

Small cell lung cancer (SCLC) accounts for approximately 15 % of all lung cancer cases. The prognosis for patients with MRL is unfavorable: the 5-year survival rate is less than 10 %. Due to the limited and low effectiveness of treatment options for SCLC, the search for more effective therapeutic approaches does not weaken. However, despite decades of basic and clinical research, little progress has been made in the treatment of MRL SCLC, leading to one of the most intractable diseases in clinical practice. In this regard, in recent years, the question arises of the need to consider the possibilities and options for combined treatment in small cell lung cancer.

Comprehensive assessment of drug consumption as a basis for pharmacotherapy optimization

2019 ◽  
pp. 22-31
Author(s):  
Olga Vyacheslavovna Zhukova
Keyword(s):  
Clinical Practice ◽  
Treatment Options ◽  
Comprehensive Assessment ◽  
Drug Consumption ◽  
Treatment Standards ◽  
Disease Epidemiology ◽  
Efficacy Analysis ◽  
Epidemiological Monitoring ◽  
Guidelines Development ◽  
Real Clinical Practice

This article describes the rationale for methodology of comprehensive assessment of drug consumption in real clinical practice. The proposed methodology includes three stages: 1) epidemiological monitoring – disease epidemiology assessment; assessment of the role of factors leading to the disease; 2) pharmacoepidemiological monitoring – assessment of pharmacotherapy in real clinical practice; clinical efficacy analysis of drugs; cost-effectiveness analysis; 3) long-term clinical and economical evaluation of various treatment options. Comprehensive assessment of drug consumption should result in optimal pharmacotherapy regimens, decrease of the drug load, increasing of the therapy effectiveness and cost reduction. The scheme of comprehensive assessment of drug consumption is universal and can be used for clinical guidelines development, treatment standards, for the optimal formation of drugs lists at the federal level. Separate stages and sub-steps of an integrated assessment also can be used at the territorial and local levels, medical institution, to optimize pharmacotherapy.

NUMERICAL COEFFICIENT FOR ENDOMETRIAL CANCER INDIVIDUAL RISK EVALUATION IN POSTMENOPAUSAL WOMEN

2017 ◽  
Vol 63 (3) ◽  
pp. 461-465
Author(s):  
Lev Bershteyn ◽  
Dmitriy Vasilev ◽  
Tatyana Poroshina ◽  
Igor Berlev
Keyword(s):  
Breast Cancer ◽  
Endometrial Cancer ◽  
Risk Evaluation ◽  
Tumor Response ◽  
Molecular Genetic ◽  
Response To Treatment ◽  
Individual Risk ◽  
The Past ◽  
Genetic Landscape ◽  
Numerical Coefficient

Increased frequency of endometrial cancer (EC) since the beginning of this century exceeds that of breast cancer and to a large extent can be attributed to dynamics of parameters, which characterize hormonal and metabolic status of ill women and molecular genetic landscape of transforming endometrium. During the past few years there are suggested several options for a personalized assessment of the risk of EC. The aim of this article is to propose and justify own version of this score with the idea of its further not only retrospective but also prospective testing both in relation to the risk of developing endometrial cancer as well as an additional marker helping to predict tumor response to treatment.

scholarly journals Implementing Personalized Medicine in COVID-19 in Andalusia: An Opportunity to Transform the Healthcare System

2021 ◽  
Vol 11 (6) ◽  
pp. 475
Author(s):  
Joaquín Dopazo ◽  
Douglas Maya-Miles ◽  
Federico García ◽  
Nicola Lorusso ◽  
Miguel Ángel Calleja ◽  
...  
Keyword(s):  
Public Health ◽  
Health Care ◽  
Clinical Practice ◽  
Personalized Medicine ◽  
Local Level ◽  
Individual Variability ◽  
Response To Therapy ◽  
Control Measures ◽  
Response To Treatment ◽  
Specific Patient

The COVID-19 pandemic represents an unprecedented opportunity to exploit the advantages of personalized medicine for the prevention, diagnosis, treatment, surveillance and management of a new challenge in public health. COVID-19 infection is highly variable, ranging from asymptomatic infections to severe, life-threatening manifestations. Personalized medicine can play a key role in elucidating individual susceptibility to the infection as well as inter-individual variability in clinical course, prognosis and response to treatment. Integrating personalized medicine into clinical practice can also transform health care by enabling the design of preventive and therapeutic strategies tailored to individual profiles, improving the detection of outbreaks or defining transmission patterns at an increasingly local level. SARS-CoV2 genome sequencing, together with the assessment of specific patient genetic variants, will support clinical decision-makers and ultimately better ways to fight this disease. Additionally, it would facilitate a better stratification and selection of patients for clinical trials, thus increasing the likelihood of obtaining positive results. Lastly, defining a national strategy to implement in clinical practice all available tools of personalized medicine in COVID-19 could be challenging but linked to a positive transformation of the health care system. In this review, we provide an update of the achievements, promises, and challenges of personalized medicine in the fight against COVID-19 from susceptibility to natural history and response to therapy, as well as from surveillance to control measures and vaccination. We also discuss strategies to facilitate the adoption of this new paradigm for medical and public health measures during and after the pandemic in health care systems.

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