Overview on Gastrointestinal Stromal Tumor; A Review

GISTs (gastrointestinal stromal tumours) are benign tumours that most usually affect the gastrointestinal (GI) system. GISTs can strike at any age, however they are most typically diagnosed in later life, with a median diagnostic age in the 60s. Abdominal ultrasound, CT scan, magnetic resonance imaging (MRI), and positron emission transverse tomography (PET) can all be used to detect GISTs (PET).CT enterography is the most effective method for determining the location of these tumors. Histopathology and immunochemistry are used to diagnose GISTs. Surgical excision remains the therapy of choice for gastrointestinal stromal tumours more than 2 cm that are readily resectable. Due to the possibility of resistance to standard treatment, mutational analysis should be undertaken when considering adjuvant and neoadjuvant therapy. In this review we’ll be looking at the disease etiology, epidemiology, diagnosis and management.

Adjuvant and neoadjuvant therapy of ER+ / HER2– breast cancer

Even early-stage breast cancer is a heterogeneous disease, so the optimal treatment depends on the pathological characteristics of the tumor. The vast majority of breast tumors (80%) are classified as estrogen receptor positive (ER+) with varying degrees of ER expression. The benefit of endocrine therapy is small with low ER staining (1–10%), occurring in less than 2% of all cases of ER+ breast cancer. Genetic analyzes are valuable for administration of adjuvant chemotherapy prior to endocrine therapy in ER+ / HER2– pN0–pN1c breast cancer. But such tests are not yet widely available. In practical work, when planning adjuvant and neoadjuvant therapy for patients with ER+ / HER2– breast cancer, pathological assessment of the expression of ER, PR, Ki‑67, as well as the tumor grade (G) remains important. The use of drugs to overcome resistance to endocrine therapy: PI3-kinase inhibitors (taselisib), CDK 4/6 inhibitors (palbociclib, abemaciclib, ribociklib), mTOR inhibitors (everolimus) can enhance the effect of neoadjuvant and adjuvant endocrine therapy.

Novel evolutionary dynamics of small populations in breast cancer adjuvant and neoadjuvant therapy

Disseminated cancer cells (DCCs) are detected in the circulation and bone marrow of up to 40% of breast cancer (BC) patients with clinically localized disease. The formation of metastases is governed by eco-evolutionary interactions of DCCs with the tissue during the transition from microscopic populations to macroscopic disease. Here, we view BC adjuvant and neoadjuvant treatments in the context of small population extinction dynamics observed in the Anthropocene era. Specifically, the unique eco-evolutionary dynamics of small asexually reproducing cancer populations render them highly vulnerable to: (1) environmental and demographic fluctuations, (2) Allee effects, (3) genetic drift and (4) population fragmentation. Furthermore, these typically interact, producing self-reinforcing, destructive dynamics—termed the Extinction Vortex—eradicating the population even when none of the perturbations is individually capable of causing extinction. We propose that developing BC adjuvant and neoadjuvant protocols may exploit these dynamics to prevent recovery and proliferation of small cancer populations during and after treatment—termed “Eco-evolutionary rescue” in natural extinctions. We hypothesize more strategic application of currently available agents based on the extinction vulnerabilities of small populations could improve clinical outcomes.

Adjuvant and neoadjuvant therapy for biliary tract cancer: a review of clinical trials

Cancer originating in the biliary tract can be classified as bile duct cancer (cholangiocarcinoma), gallbladder cancer, or ampullary cancer. Bile duct cancer is further divided to intrahepatic, perihilar and distal bile duct subtypes according to the anatomical location of the tumor. The biological characteristics of each tumor are heterogeneous. However, because of the rarity of each disease, the efficacy of new drugs has been tested in groups of patients with different biliary tract cancers. In patients with metastatic or recurrent biliary tract cancer, recent randomized clinical trials revealed the non-inferiority of gemcitabine + S-1 and the superiority of gemcitabine + cisplatin + S-1 compared with gemcitabine + cisplatin in terms of overall survival, thereby establishing a new standard treatment. In the field of adjuvant therapy for biliary tract cancer, the British BILCAP (capecitabine compared with observation in resected biliary tract cancer) study revealed longer median overall survival in the capecitabine group than in the observation group in the per-protocol analysis (but not in the intention-to-treat analysis), bringing a shift toward postoperative management. Several other studies of adjuvant therapy are ongoing, and they may lead to reforms in treatment strategy for resectable biliary tract cancer in the future. The use of neoadjuvant therapy for biliary tract cancer is in its infancy, but it is expected to overcome the limitations of adjuvant therapy for this malignancy. In this review, we summarized the evidence available from clinical trials of adjuvant and neoadjuvant therapy for biliary tract cancer and described ongoing clinical trials.