NUTRITIONAL THERAPY IN PATIENTS WITH STOMACH CANCER

This study aims to evaluate how food and nutrition can improve the quality of life of people with gastric cancer, since these patients are faced with various nutritional problems, among them, low weight, and malnutrition. The study is methodologically constituted as a qualitative approach and bibliographical research. The techniques used were discussion and interpretation from the reading of articles on the subject published in SCIELO (Scientific Electronic Library), Pub Med., Service of the National Library of Medicine). exploring the data of the results that discuss the subject in question. The study found that nutritional care leads to an improvement and well-being in the quality of life of patients affected by stomach cancer. Thus, nutritional monitoring can provide a reduction in the adverse effects of treatment and the risk of malnutrition, improving treatment tolerance, quality of life and prognosis.

Submicron particle docetaxel intratumoral injection in combination with anti-mCTLA-4 into 4T1-Luc orthotopic implants reduces primary tumor and metastatic pulmonary lesions

We describe here characterization of the response of local and metastatic disease and immunomodulation following intratumoral (IT) injection of submicron particle docetaxel (SPD) administered alone or in combination with systemic antibody anti-mCTLA-4 (anti-mCTLA-4) in the metastatic 4T1-Luc2-1A4 (4T1) murine breast cancer model. In-life assessments of treatment tolerance, tumor volume (TV), and metastasis were performed (n = 10 animals/group). At study end, immune cell populations in tumor-site tissues and peripheral blood were analyzed using flow cytometry. Signs of distress typical of this aggressive tumor model occurred across all animals except for the combination treated which were asymptomatic and gained weight. TV at study end was significantly reduced in the combination group versus untreated [43% reduced (p < 0.05)] and vehicle controls [54% reduced (p < 0.0001)]. No evidence of thoracic metastasis was found in 40% of combination group animals and thoracic bioluminescence imaging (BLI) was reduced vs. untreated controls (p < 0.01). Significant elevations (p < 0.05) in CD4 + T, CD4 + helper T, Treg, and NKT cells were found in tumor and blood in SPD or combination treatment compared to controls or anti-mCTLA-4. Combination treatment increased tumor-associated CD8 + T cells (p < 0.01), peripheral B cells (p < 0.01), and tumor associated and circulating dendritic cells (DC) (p < 0.05). Tumor-associated NK cells were significantly increased in SPD ± anti-mCTLA-4 treatments (p < 0.01). Myeloid-derived suppressor cells (MDSC) were reduced in bloods in SPD ± anti-mCTLA-4 groups (p < 0.05). These data demonstrate that both SPD and anti-mCTLA-4 produce local anti-tumor effects as well as reductions in metastasis which are significantly enhanced when administered in combination.

Tumor Microenvironment Autophagic Processes and Cachexia: The Missing Link?

Cachexia is a syndrome that affects the entire organism and presents a variable plethora of symptoms in patients, always associated with continuous and involuntary degradation of skeletal muscle mass and function loss. In cancer, this syndrome occurs in 50% of all patients, while prevalence increases to 80% as the disease worsens, reducing quality of life, treatment tolerance, therapeutic response, and survival. Both chronic systemic inflammation and immunosuppression, paradoxically, correspond to important features in cachexia patients. Systemic inflammation in cachexia is fueled by the interaction between tumor and peripheral tissues with significant involvement of infiltrating immune cells, both in the peripheral tissues and in the tumor itself. Autophagy, as a process of regulating cellular metabolism and homeostasis, can interfere with the metabolic profile in the tumor microenvironment. Under a scenario of balanced autophagy in the tumor microenvironment, the infiltrating immune cells control cytokine production and secretion. On the other hand, when autophagy is unbalanced or dysfunctional within the tumor microenvironment, there is an impairment in the regulation of immune cell’s inflammatory phenotype. The inflammatory phenotype upregulates metabolic consumption and cytokine production, not only in the tumor microenvironment but also in other tissues and organs of the host. We propose that cachexia-related chronic inflammation can be, at least, partly associated with the failure of autophagic processes in tumor cells. Autophagy endangers tumor cell viability by producing immunogenic tumor antigens, thus eliciting the immune response necessary to counteract tumor progression, while preventing the establishment of inflammation, a hallmark of cachexia. Comprehensive understanding of this complex functional dichotomy may enhance cancer treatment response and prevent/mitigate cancer cachexia. This review summarizes the recent available literature regarding the role of autophagy within the tumor microenvironment and the consequences eliciting the development of cancer cachexia.

Treatment of AML in Older Patients

Acute myeloid leukaemia (AML) is a disease mostly diagnosed in older adults. Treatment of older patients with AML remains challenging with higher rates of intrinsic chemotherapeutic resistance and decreased treatment tolerance. Indeed AML in older patients has different clinical and biologic characteristics compared to younger patients. Several treatment options are available for treatment of AML in older patients, namely conventional intensive chemotherapy (‘3 + 7’), low-dose cytarabine, and hypomethylating agents. Combinations with new drugs have been recently approved or are in advanced stages of clinical testing, namely venetoclax, midostaurin, glasdegib. Clinical decision making should take into account disease characteristics (e.g. cytogenetic and molecular abnormalities, white blood cell count), patient characteristics (e.g. performance, comorbidities, geriatric assessment) and patients’ preference when considering which treatment option is most suitable for the older patient. Allogeneic haematopoietic cell transplantation (HCT) as post-remission strategy should also be considered for older patients with AML. Allogeneic HCT following reduced-intensity conditioning or non-myeloablative conditioning has made this treatment option more suitable for older patients with a reduction in treatment-related mortality.

Efficacy of a novel topical combination of esafoxolaner, eprinomectin and praziquantel against fleas in cats, under field conditions

Esafoxolaner is a purified afoxolaner enantiomer with insecticidal and acaricidal properties. It is combined with eprinomectin and praziquantel, nematodicidal and cestodicidal compounds, in a novel topical endectoparasiticide formulation for cats. This novel formulation was tested in four field studies, in the United States, Europe, Japan and Australia. In all studies, naturally flea-infested domestic cats were treated with the novel formulation at the label dose and conditions of use. The main objective, identical in the four studies, was to assess efficacy on fleas, based on comparison of mean number of fleas found on infested cats before and one month after treatment. Tolerance to the product was also evaluated in the four studies. Otherwise, the studies had some differences in their design and secondary objectives, for example testing for a reduction in flea infestation-related cutaneous signs, testing of one treatment or of three monthly treatments, and use of a positive control group. In the four studies, a total of 307 cats were treated with the novel formulation. The reduction of fleas one month after treatment was 97.7%, 98.8%, 100% and 99.7% in the United States, Europe, Japan and Australia, respectively. There were no significant health abnormalities attributed to treatment in any of the studies.

The efficacy of immunonutrition in improving tolerance to chemoradiotherapy in patients with head and neck cancer, receiving nutritional counseling: study protocol of a randomized, open-label, parallel group, bicentric pilot study

Background: Nutritional support, including nutritional counseling and oral nutritional supplements (ONSs), has been recommended at the earliest opportunity in head and neck (H&N) cancer patients. The limited available evidence on the efficacy of immunonutrition during chemoradiotherapy (CT-RT) in H&N cancer patients is positive with regard to some secondary endpoints, but is still scanty, particularly with regard to toxicity and treatment tolerance. We hypothesize that early systematic provision of ONSs with a high-protein–high-calorie mixture containing immunonutrients (Impact) compared to standard high-calorie–high-protein nutritional blends, in addition to nutritional counseling, may be beneficial to patients with H&N cancer during CT-RT. Hence, we designed the present study to evaluate the efficacy, in terms of treatment tolerance, toxicity and response, body weight, body composition, protein-calorie intake, quality of life (QoL), fatigue, muscle strength and immunological profile of the early systematic provision of ONSs enriched in immunonutrients compared to isonitrogenous standard blends, in H&N cancer patients undergoing CT-RT. Methods: This is a pragmatic, bicentric, randomized (1:1), parallel-group, open label, controlled, pilot clinical trial. Discussion: Many efforts are still to be taken to improve the efficacy of nutritional support in oncology. Immunonutrition represents a promising approach also in H&N cancer patients, but the evidence on its efficacy in improving clinical outcomes during CT-RT is still inconclusive. The present pilot study, which guarantees the early provision of nutritional assessment and support to all the enrolled patients in accordance with the recent guidelines and recommendations, could represent one of the first proofs of the clinical effectiveness of early oral immunonutrition in cancer patients undergoing CT-RT and could stimulate further large randomized trials, potentially resulting in the improvement of supportive care quality. Trial registration: This study is registered on ClinicalTrials.gov Identifier: NCT04611113.

Impact of IL-2 on Treatment Tolerance in Patients With High-Risk Neuroblastoma Treated With Dinutuximab Beta-Based Immunotherapy

Patients with high-risk neuroblastoma treated with continuous long-term infusion of anti-GD2 antibody dinutuximab beta (DB) in combination with IL-2 show an acceptable safety profile. Here, we compared treatment tolerance with and without IL-2. Ninety-nine patients with high-risk neuroblastoma received up to five cycles of DB given as long-term infusion (10 mg/m2/d, 100 mg/m2; per cycle) with IL-2 (53 patients; regimen A; 6 × 106 IU/m2/d; 60 × 106 IU/m2/cycle) and without IL-2 (46 patients; regimen B) in a single-center compassionate use program. Clinical parameters (body temperature, vital signs, Lansky performance score), laboratory values [C-reactive protein, IFN-γ, IL-6, and IL-18 (cycle 1)], and requirement of i.v. co-medication (e.g., morphine, metamizole) were systematically assessed. Patients with stable clinical parameters and that did not require co-medication were defined as potential “outpatient candidates.” Patients showed higher levels of body temperature and CRP in regimen A compared to B. However, IL-6 serum concentrations were similar in pts of both cohorts in the first cycle. Patients receiving regimen B showed a shorter time to achieve normal vital parameters and required less co-medication compared to patients in regimen A that resulted in a shorter median time period to discharge and to achieve a potential outpatient status (6d regimen A and 3–5d regimen B after start of antibody infusion, respectively). This study shows that omitting IL-2 from immunotherapy with DB allows reduced co-medication and hospitalization time and therefore results in improved quality of life in patients with high-risk neuroblastoma.

Impact of Exercise on Chemotherapy Tolerance and Survival in Early-Stage Breast Cancer: A Nonrandomized Controlled Trial

Background: Available preliminary evidence is conflicting on whether exercise can positively influence antineoplastic treatment tolerance and in turn improve survival. Patients and Methods: This study compared chemotherapy treatment tolerance and survival among women receiving adjuvant chemotherapy for early-stage breast cancer who participated in a single-arm trial of supervised aerobic and resistance exercise programming versus a historical cohort that did not receive structured exercise programming. Results: The exercise group (EX; n=73) and control group (CTR; n=85) participants were matched on age and treatment and balanced on medical history, cancer diagnosis, and body mass index. Attendance in the EX group was 64% ± 27% of 3 offered sessions per week. For all chemotherapy agents combined, the relative risk (RR) of a chemotherapy dose reduction (RR, 0.78; 95% CI, 0.54–1.11) or delay (RR, 1.05; 95% CI, 0.62–1.80) did not differ between groups. However, the EX group had reduced relative and absolute risks of a dose reduction in doxorubicin by 60% and 18%, respectively. For all agents combined, there were no differences between groups in risk of anemia, neutropenia, or weight gain. In the EX group, dose reductions due to neutropenia (P=.027), other infections (P=.049), and fatigue (P=.037) were less common, whereas mucositis was more common (P=.023), compared with the CTR group. The EX group had reduced relative and absolute risks of weight gain on the docetaxel + cyclophosphamide regimen by 38% and 30%, respectively. After a median follow-up of 70 months (range, 54–84 months), there was no difference between the EX and CTR groups in disease-free survival events (n=8 [11%] vs n=9 [11%], respectively; log-rank test, P=.78) or overall survival events (n=5 [7%] vs n=6 [7%], respectively; log-rank test, P=.974). Conclusions: Overall, exercise programming during adjuvant chemotherapy does not appear to impact treatment tolerance or survival in women receiving common modern regimens of adjuvant chemotherapy for early-stage breast cancer. However, exercise may provide selective benefits, depending on the treatment regimen received.