Antidiabetics, Anthelmintics, Statins, and Beta-Blockers as Co-Adjuvant Drugs in Cancer Therapy.

Over the last years, repurposed agents have provided growing evidence of fast implementation in oncology treatment such as certain antimalarial, anthelmintic, antibiotics, anti-inflammatory, antihypertensive, antihyperlipidemic, antidiabetic agents. In this study, the four agents of choice were present in our patients' daily treatment for nonmalignant-associated pathology and have known, light toxicity profiles. It is quite common for a given patient's daily administration schedule to include two or three of these drugs for the duration of their treatment. We chose to review the latest literature concerning metformin, employed as a first-line treatment for type 2 diabetes; mebendazole, as an anthelmintic; atorvastatin, as a cholesterol-lowering drug; propranolol, used in cardiovascular diseases as a nonspecific inhibitor of beta-1 and beta-2 adrenergic receptors. At the same time, certain key action mechanisms make them feasible antitumor agents such as for mitochondrial ETC inhibition, activation of the enzyme adenosine monophosphate-activated protein kinase, amelioration of endogenous hyperinsulinemia, inhibition of selective tyrosine kinases (i.e., VEGFR2, TNIK, and BRAF), and mevalonate pathway inhibition. Despite the abundance of results from in vitro and in vivo studies, the only solid data from randomized clinical trials confirm metformin-related oncological benefits for only a small subset of nondiabetic patients with HER2-positive breast cancer and early-stage colorectal cancer. At the same time, clinical studies confirm metformin-related detrimental/lack of an effect for lung, breast, prostate cancer, and glioblastoma. For atorvastatin we see a clinical oncological benefit in patients and head and neck cancer, with a trend towards radioprotection of critical structures, thus supporting the role of atorvastatin as a promising agent for concomitant association with radiotherapy. Propranolol-related increased outcomes were seen in clinical studies in patients with melanoma, breast cancer, and sarcoma.

When Should We Expect Curative Results of Neoadjuvant Treatment in Locally Advanced Rectal Cancer Patients?

This review on recently published literature aims to summarize published data on pathologic complete response following neoadjuvant treatment in biopsy proven locally advanced rectal cancer patients. Published articles referring to pCR rectal cancer patients were identified using PubMed search. Eleven relevant articles were selected, based on tumor, treatment, and patient characteristics reporting. As a conclusion, rectal cancer patients with the highest chances of complete clinical or pathological response to neoadjuvant treatment are males, who are around 60 years, diagnosed with well or moderate differentiated locally advanced rectal cancer.

Risk of Myelopathy Following Second Local Treatment after Initial Irradiation of Spine Metastasis.

Metastatic lesions of the spine occur in up to 40% of cancer patients and are a frequent source of pain and neurologic deficit due to cord compression. Palliative radiotherapy is the main first-intent local treatment in the form of single-fraction radiotherapy or fractionated courses. Reirradiation is a viable option for inoperable patients where spinal decompression is needed but with an increased risk of radiation-induced myelopathy (RM) and subsequent neurologic damage. This review summarizes reported data on local treatment options after initial irradiation in patients with relapsed spine metastasis and key dosimetric correlations between the risk of spinal cord injury and reirradiation technique, total dose, and time between treatments. The Linear Quadratic (LQ) model was used to convert all the published doses into biologically effective doses and normalize them to EQD2. For 3D radiotherapy, authors used cumulative doses from 55.2 Gy2/2 to 65.5 Gy2/2 EQD2 with no cases of RM mentioned. We found little evidence of RM after SBRT in the papers that met our criteria of inclusion, usually at the median reported dose to critical neural tissue around 93.5 Gy2/2. There is a lack of consistency in reporting the spinal cord dose, which leads to difficulty in pooling data.

Prognostic Role of Vascular Endothelial Growth Factor and Correlation with Oxidative Stress Markers in Locally Advanced and Metastatic Ovarian Cancer Patients.

BACKGROUND: Vascular endothelial growth factor (VEGF) plays an important role in tumor progression in ovarian cancer, but the complex mechanism and interaction with oxidative stress are not fully understood. METHODS: A prospective study included 52 patients with ovarian adenocarcinoma stage IIIA-IV. Serum VEGF and reactive oxygen species (ROS) such as malondialdehyde and ceruloplasmin were measured. RESULTS: VEGF levels were elevated (mean 1014.7 ± 165 pg/mL), especially in patients with macroscopic residual disease (1058 vs. 810 pg/mL, p = 0.0001). Median progression-free survival (PFS) and overall survival (OS) were 6 and 40 months in patients with a very high VEGF (over 1200 pg/mL), 11 and 48 months in patients with VEGF between 1000-1200 pg/mL, 18 and 84 months in patients with VEGF between 800-1000 pg/mL, and not reached in patients with normal VEGF. Increased VEGF values were associated with a 2.6-fold increased risk of disease progression (HR = 2.60, 95% CI 1.69-3.99), and a 1.4-fold increased risk of death (HR = 1.4, 95% CI 1.15-1.91, p = 0.002). Receiver operator characteristic (ROC) curves were used to validate VEGF as a prognostic factor and the area under the curve (AUC) was 0.814, p = 0.036 for PFS and 0.729, p = 0.043, for OS. There was a positive correlation between VEGF and malondialdehyde, Pearson coefficient of 0.35, p = 0.0001. CONCLUSIONS: VEGF and malondialdehyde are important prognostic markers in ovarian cancer, especially in macroscopic residual disease, and there is a positive correlation between angiogenesis and oxidative stress.

Impact of the COVID-19 Pandemic on Treatment and Oncologic Outcomes for Cancer Patients in Romania.

BACKGROUND/AIM: This study aimed to assess the impact of the ongoing COVID-19 pandemic on cancer patients, known to be immune-compromised due to the disease itself, oncological treatments and adjuvant medicines use such as steroids. Overall survival was determined for patients with COVID-19 infection and stratification according to known comorbidities and complications was performed. PATIENTS AND METHODS: This prospective study included ninety cancer patients with COVID-19 confirmed by PCR testing performed before each cycle of chemotherapy or every two weeks during radiotherapy between May and December 2020 in two tertiary Cancer Centers. Demographic, cancer-related and SARS-CoV-2 infection data were collected and long-term oncologic outcome was assessed. RESULTS: Mean age of cancer patients diagnosed with SARS-CoV-2 was 59.7±12.1 years (range=30-83 years). Fifty-two (57.7%) were women. The most frequent cancer localization was breast (n=28, 31.1%) followed by colorectal (n=11, 12.2%) and lung cancer (n=8, 8.8%). Most patients infected with SARS-CoV-2 were diagnosed in stage IV of the disease (n=44, 48.9%) followed by stage III (n=19, 21.1%) and stage II disease (18.9%). Regarding comorbidities, the most common was hypertension (n=31) followed by cardiac dysfunction (n=23) and type II diabetes (n=13). Of 27 (30%) patients who needed hospitalization, 4 patients developed severe infection, 17 patients had mild symptoms and 6 patients were minimally symptomatic. After a median follow-up of 22.5 months, 5 patients (5.55%) died due to SARS-COV-2 infection, all stages III and IV. Median estimated overall survival was 14 months in patients who died because of COVID infection compared to 98 months in cancer-related mortality analysis (p<0.0001). Three deaths occurred during chemotherapy, 1 death in the chemoradiotherapy radiotherapy group. CONCLUSION: SARS-CoV-2 infection was associated with an excess mortality in our study population, especially in patients with advanced and metastatic disease and in those receiving immunosuppressive treatment such as chemotherapy and radiotherapy.

Changing the Prognosis of Metastatic Cervix Uteri Adenosquamous Carcinoma through a Multimodal Approach: A Case Report.

Adenocarcinoma and adenosquamous carcinoma (AS) are 2 rare histological types of cervix uteri cancer constituting almost 20% of all cervix cancers, leading to a lack in patient management guidelines. We report the case of a 32-year-old woman with an oligometastatic cervix AS for which a multimodal treatment approach was used. Despite the patient's bad prognosis, a complete response was achieved, which further resulted in excellent local control and prolonged survival. This case report serves the purpose of encouraging multidisciplinary team work and out-of-the-box thinking that should result in an individualized treatment for rare cancer subtypes.