Early Echocardiography and ECG Changes Following Radiotherapy in Patients with Stage II-III HER2-Positive Breast Cancer Treated with Anthracycline-Based Chemotherapy with or without Trastuzumab-Based Therapy.

BACKGROUND Cardiotoxicity from radiotherapy and anti-cancer therapies have been reported in patients with breast cancer. This study aimed to investigate the early echocardiography and ECG changes following radiotherapy in 68 patients ages 30-78 years with stages II-III HER2-positive breast cancer treated with anthracycline-based chemotherapy with or without trastuzumab-based therapy from 2015 to 2021. MATERIAL AND METHODS We analyzed data of 68 breast cancer patients aged 30-78 years, predominantly in AJCC stages II-III (61) and HER2-positive (58), treated and monitored from 2015 to 2021. Cardiac function was assessed using echo- and electrocardiography. We employed univariate logistic models to gauge associations between pre-existing cardiac conditions, treatment modalities, and changes in cardiac function. RESULTS A decrease in the left ventricle ejection fraction (EF) by >5% was associated with heart doses >49.3 Gy and with maximum and average doses to the left anterior descending artery (LAD) exceeding 46.9 Gy and 32.7 Gy, respectively. An EF drop of ≥10% was correlated with anti-HER2 therapy, pre-existing ECG changes, and the onset of conditions in the left ventricle, major vessels, and valves. Conditions were exacerbated in patients with prior echocardiographic abnormalities, while some emerged concurrent with the EF decline. CONCLUSIONS This research emphasizes the importance of personalized heart monitoring and care for breast cancer patients undergoing multimodal therapies. Significant and potentially irreversible EF declines can result from radiation and anti-HER2 treatments.

Validation of a New Prognostic Score in Patients with Ovarian Adenocarcinoma.

Background and Objectives: This study aimed to assess the impact of clinical prognostic factors and propose a prognostic score that aids the clinician's decision in estimating the risk for patients in clinical practice. Materials and Methods: The study included 195 patients diagnosed with ovarian adenocarcinoma. The therapeutic strategy involved multidisciplinary decisions: surgery followed by adjuvant chemotherapy (80%), neoadjuvant chemotherapy followed by surgery (16.4%), and only chemotherapy in selected cases (3.6%). Results: After a median follow-up of 68 months, in terms of progression-free survival (PFS) and overall survival (OS), Eastern Cooperative Oncology Group (ECOG) performance status of 1 and 2 vs. 0 (hazard ratio-HR = 2.71, 95% confidence interval-CI, 1.96-3.73, p < 0.001 for PFS and HR = 3.19, 95%CI, 2.20-4.64, p < 0.001 for OS), menopausal vs. premenopausal status (HR = 2.02, 95%CI, 1.35-3,0 p < 0.001 and HR = 2.25, 95%CI = 1.41-3.59, p < 0.001), ascites (HR = 1.95, 95%CI 1.35-2.80, p = 0.03, HR = 2.31, 95%CI = 1.52-3.5, p < 0.007), residual disease (HR = 5.12, 95%CI 3.43-7.65, p < 0.0001 and HR = 4.07, 95%CI = 2.59-6.39, p < 0.0001), and thrombocytosis (HR = 2.48 95%CI = 1.72-3.58, p < 0.0001, HR = 3.33, 95%CI = 2.16-5.13, p < 0.0001) were associated with a poor prognosis. An original prognostic score including these characteristics was validated using receiver operating characteristic (ROC) curves (area under the curve-AUC = 0.799 for PFS and AUC = 0.726 for OS, p < 0.001). The median PFS for patients with none, one, two, three, or four (or more) prognostic factors was not reached, 70, 36, 20, and 12 months, respectively. The corresponding median overall survival (OS) was not reached, 108, 77, 60, and 34 months, respectively. Conclusions: Several negative prognostic factors were identified: ECOG performance status ≥ 1, the presence of ascites and residual disease after surgery, thrombocytosis, and menopausal status. These led to the development of an original prognostic score that can be helpful in clinical practice.

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.

Long-Term Outcome of Patients with Stage II and III Muscle-Invasive Urothelial Bladder Cancer after Multimodality Approach. Which Is the Best Option?

Background and Objectives: There is no consensus regarding the optimal therapy sequence in stage II and III bladder cancer. The study aimed to evaluate the long-term oncologic outcomes in patients with bladder cancer after a multimodality approach. Materials and methods: Medical files of 231 consecutive patients identified with stage II (46.8%), IIIA (30.3%), and IIIB (22.9%) transitional cell carcinoma of the bladder (BC) treated with a multimodality approach were retrospectively reviewed. The treatment consisted of transurethral resections or cystectomy, radiotherapy alone or concurrent chemoradiotherapy as definitive treatment, or neoadjuvant chemotherapy using platinum salt regimens. Results: Median age at diagnosis was 65 ± 10.98 years. Radical or partial cystectomy was performed in 88 patients (37.1%), and trans-urethral resection of bladder tumor (TURBT) alone was performed in 143 (61.9%) patients. Overall, 40 patients (17.3%) received neoadjuvant chemotherapy and 82 (35.5%) received definitive chemoradiotherapy. After a median follow-up of 30.6 months (range 3-146 months), the median disease-free survival (DFS) for an entire lot of patients was 32 months, and the percentage of patients without recurrence at 12, 24, and 36 months was 86%, 58%, and 45%, respectively. Patients receiving neoadjuvant chemotherapy had a better oncologic outcome compared to patients without neoadjuvant chemotherapy (median DFS not reached vs. 31 months, p = 0.038, HR = 0.55, 95% CI 0.310-0.951). There was a trend for better 3-year DFS with radical cystectomy vs. TURBT (60 months vs. 31 months, p = 0.064). Definitive chemoradiotherapy 3-year DFS was 58% compared to 44% in patients who received radiotherapy or chemotherapy alone. Conclusions: In patients with stages II and III, both neoadjuvant chemotherapy and concurrent radio-chemotherapy are valid options for treatment and must be part of a multidisciplinary approach.

Tumor is an Oxidative Stress Factor in Ovarian Cancer Patients.

Introduction: Epithelial ovarian cancer is worldwide the second cause of gynaecological cancer but the commonest cause of gynaecological cancer-associated death. AIM: To determine the intensity of oxidative stress in ovarian cancer patients and to establish a connection between the presence of the tumor and reactive oxygen species (ROS). PATIENTS AND METHODS: Thirty-five patients diagnosed with epithelial ovarian carcinoma stage II-IV between 2010 and 2017, who underwent multimodality treatment (surgery and chemotherapy) were included in the study. ROS measured in dynamic (four determinations between every cycle) were malondialdehyde to evaluate the lipid peroxidation, ceruloplasmin, SH- albumin thiols groups and total antioxidants. Results: There was an increase in the value of ROS: malondialdehyde mean value was 8.1 µmol/100 ml (normal value 4 µmol/100 ml); ceruloplasmin mean value was 144.8U.I. (normal value 120U.I), both showing an active oxidative process in patients with ovarian cancer. A small decrease of the value of thiols (395 vs. 450 µmol/l) and a small increase of total antioxidants was noticed (1.44 vs. 1.4 µmol). All four compounds decrease between the first determination and the fourth one. There was a strong correlation between lipid peroxides levels and ceruloplasmin (Pearson correlation 0.315 p=0.005) and between lipid peroxides and thiols groups (Pearson correlation 0.23 p=0.039). There was a correlation between thiols and antioxidants (Pearson correlation 0.33 p=0.003). Lipid peroxidation and ceruloplasmin were significantly higher in patients with residual disease (p=0.039, p=0.046) emphasizing that the tumor is a generator of oxidative stress. CONCLUSION: Tumor produces ROS in excess in patients with advanced ovarian adenocarcinoma. Those ROS are corelated and acts as signalling molecules.

Distant Oncologic Outcome of Patients with Locally Advanced Unresectable and Metastatic Esophageal Cancer after Multimodality Treatment.

Background: Combined modality therapy has been employed for the treatment of choice for locally advanced esophageal and eso-gastric junction cancers all around the globe but a unanimous consensus is missing. Methods: Medical files of 132 patients with confirmed locally advanced un-resectable, and metastatic esophageal cancer who presented to our center between 2010-2015 were retrospectively reviewed. Multimodality treatment consisting of chemo-radiotherapy or chemotherapy or radiotherapy alone and surgery in patients who convert to operability was planned according to tumor extend and performance status of the patient. Results: Seventy seven percent of the patient presented with squamous carcinoma and 23 % were adenocarcinoma. At the diagnosis 22 patients (16.6%) were stage IV. Concurrent chemoradiotherapy was administered in 26 patients (19.7%), chemotherapy in 91 patients (68.9%), radiotherapy in 83 patients (62.9%). After combined treatment, surgery with radical intent was possible in 21 patients (15.9%). After a follow up of 17.3 months, overall survival (OS) was 12 months, with one and two-year survival rate of 49.2% and 17.4%. In metastatic patients OS was 10 months. Patients who were converted to operability had a OS of 20 months vs. 10 months in patients who doesn't undergo surgery (p=0.002). Chemo-radiotherapy was superior in terms of OS compare with chemotherapy or radiotherapy administered sequential (17 vs. 10 months, p=0.013). Conclusions: Multimodality treatment in locally advanced esophageal cancers (concurrent radiochemotherapy followed by surgery) can be considered superior to each method as single therapy and radiotherapy and chemotherapy can make certain locally advanced esophageal tumors resectable.

Cancer Screening: Present Recommendations, the Development of Multi-Cancer Early Development Tests, and the Prospect of Universal Cancer Screening.

Cancer continues to pose a considerable challenge to global health. In the search for innovative strategies to combat this complex enemy, the concept of universal cancer screening has emerged as a promising avenue for early detection and prevention. In contrast to targeted approaches that focus on specific populations or high-risk individuals, universal screening seeks to cast a wide net to detect incipient malignancies in different demographic groups. This paradigm shift in cancer care underscores the importance of comprehensive screening programs that go beyond conventional boundaries. As our understanding of the complex molecular and genetic basis of cancer deepens, the need to develop comprehensive screening methods becomes increasingly apparent. In this article, we look at the rationale and potential benefits of universal cancer screening.

Predictors of Clinical Hematological Toxicities under Radiotherapy in Patients with Cervical Cancer-A Risk Analysis.

BACKGROUND: Cervical cancer ranks third in frequency among female cancers globally and causes high mortality worldwide. Concurrent chemoradiotherapy improves the overall survival in cervical cancer patients by 6% but it can cause significant acute and late toxicities affecting patient quality of life. Whole pelvis radiotherapy doses of 10-20 Gy can lead to myelosuppression and to subsequent hematological toxicities since pelvic bones contain half of bone marrow tissue. METHODS: A total of 69 patients with IB-IVB-staged cervical cancer have been included in this retrospective cohort study. We analyzed clinical adverse events and changes in blood cell counts (hemoglobin, neutrophils, leukocytes, and platelets) during radiation or chemoradiotherapy received at the Oncological Institute of Bucharest from 2018 to 2021. RESULTS: Decreases in hemoglobin levels of over 2.30 g/dL during treatment were associated with BMI > 23.2 kg/m2 (OR = 8.68, 95%CI = [1.01, 75.01]), age over 53 years (OR = 4.60 95%CI = [1.10, 19.22]), with conformational 3D irradiation (OR = 4.78, 95%CI = [1.31, 17.40]) and with total EQD2 of over 66.1 Gy (OR = 3.67, 95%CI = [1.02, 13.14]). The hemoglobin decrease rate of 0.07 g/dL/day was related to 95% isodose volume (OR = 18.00). Neutropenia is associated frequently with gastrointestinal side effects and with the bowel and rectal V45 isodoses (OR = 16.5 and OR = 18.0, respectively). Associations of total external and internal radiation dose with the time durations calculated from the initiation of treatment to the onset of hematological adverse reactions were also obtained. The maximum drop in leukocytes was observed before day 35 from the RT initiation in patients who underwent treatment with 3D conformal radiotherapy (OR = 4.44, 95%CI = [1.25, 15.82]). Neutrophil levels under 2.2 × 103/µL and thrombocyte levels under 131 × 103/µL during the follow-up period were associated with a total planned dose of 54 Gy to the pelvic region volume (OR = 6.82 and OR = 6.67, respectively). CONCLUSIONS: This study shows the existence of clinical and blood predictors of hematological adverse reactions in cervical cancer patients. Thus, patients who are in a precarious clinical situation, with low hematological values (but not yet abnormal), should be monitored during days 29-35 after the initiation of RT, especially if they are obese or over 53 years of age.

Quantitative vs. Qualitative SPECT-CT Diagnostic Accuracy in Bone Lesion Evaluation-A Review of the Literature.

(1) Background: Considering the importance that quantitative molecular imaging has gained and the need for objective and reproducible image interpretation, the aim of the present review is to emphasize the benefits of performing a quantitative interpretation of single photon emission computed tomography-computed tomography (SPECT-CT) studies compared to qualitative interpretation methods in bone lesion evaluations while suggesting new directions for research on this topic. (2) Methods: By conducting comprehensive literature research, we performed an analysis of published data regarding the use of quantitative and qualitative SPECT-CT in the evaluation of bone metastases. (3) Results: Several studies have evaluated the diagnostic accuracy of quantitative and qualitative SPECT-CT in differentiating between benign and metastatic bone lesions. We collected the sensitivity and specificity for both quantitative and qualitative SPECT-CT; their values ranged between 74-92% and 81-93% for quantitative bone SPECT-CT and between 60-100% and 41-100% for qualitative bone SPECT-CT. (4) Conclusions: Both qualitative and quantitative SPECT-CT present an increased potential for better differentiating between benign and metastatic bone lesions, with the latter offering additional objective information, thus increasing diagnostic accuracy and enabling the possibility of performing treatment response evaluation through accurate measurements.

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.

Quantitative Assessment of Treatment Response in Metastatic Breast Cancer Patients by SPECT-CT Bone Imaging-Getting Closer to PET-CT.

BACKGROUND: Cancer represents the major cause of death mainly through its ability to spread to other organs, highlighting the importance of metastatic disease diagnosis and accurate follow up for treatment management purposes. Although until recently the main method for imaging interpretation was represented by qualitative methods, quantitative analysis of SPECT-CT data represents a viable, objective option. METHODS: Seventy-five breast cancer patients presenting metastatic bone disease underwent at least two Bone SPECT-CT studies using [99mTc]-HDP between November 2019 to October 2022. RESULTS: Our findings show a good positive relationship between the qualitative methods of imaging interpretation and quantitative analysis, with a correlation coefficient of 0.608 between qualitative whole body scintigraphy and quantitative SPECT-CT, and a correlation coefficient of 0.711 between the qualitative and quantitative interpretation of SPECT-CT data; nevertheless, there is a need for accurate, objective and reproducible methods for imaging interpretation, especially for research purposes. CONCLUSIONS: Quantitative evaluation of the SPECT-CT data has the potential to be the first choice of imaging interpretation for patient follow up and treatment response evaluation, especially for research purposes, because of its objectivity and expression of uptake changes in absolute units.

The Efficacy of Immunotherapy in Long-Term Survival in Non-Small Cell Lung Cancer (NSCLC) Associated with the Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH).

INTRODUCTION: The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the most common cause of hyponatremia in cancer patients, occurring most frequently in patients with small cell lung cancer. However, this syndrome occurs extremely rarely in patients with non-small cell lung cancer. The results of the clinical trials have revealed that immuno-oncological therapies are effective for long periods of time, providing hope for long survival and with a good quality of life. CASE PRESENTATION: We present the case of a female patient who was 62 years old at the time of diagnosis in 2016 who underwent surgery for a right pulmonary tumor (pulmonary adenocarcinoma) and subsequently underwent adjuvant chemotherapy. The patient had a left inoperable mediastinohilar relapse in 2018, which was treated using polychemotherapy The patient also had an occurrence of progressive metastasis and a syndrome of inappropriate antidiuretic hormone secretion (SIADH) in 2019 for which immunotherapy was initiated. The patient has continued with immunotherapy until the time this study began to be written (April 2023), the results being the remission of hyponatremia, the clinical benefits and long-term survival. DISCUSSION: The main therapeutic option for SIADH in cancer patients is the treatment of the underlying disease, and its correction depends almost exclusively on a good response to oncological therapy. The initiation of immunotherapy at the time of severe hyponatremia occurrence led to its remission as well as the remission of the other two episodes of hyponatremia, which the patient presented throughout the evolution of the disease, demonstrating an obvious causal relationship between SIADH and the favorable response to immunotherapy. CONCLUSIONS: Each patient must be approached individually, taking into account the various particular aspects. Immunotherapy proves to be the innovative treatment that contributes to increasing the survival of patients with metastatic non-small cell lung cancer and to increasing their quality of life.

RediScore: Prospective validation of a pipeline for homologous recombination deficiency analysis.

Tumors harboring homologous recombination deficiency (HRD) are considered optimal candidates for poly(ADP-ribose) polymerase 1 (PARP) inhibitor treatment. Such deficiency can be detected by analyzing breast cancer type (BRCA)1/2 gene mutations, as well as mutations in other genes of the homologous recombination pathway. The algorithmic measurement of the HRD effect by identifying genomic instability (GI) has been used as biomarker. As compared with the direct measurement of somatic gene alterations, this approach increases the number of patients who could benefit from PARP inhibitor treatment. In the present study, the performance of the Oncoscan CNV assay, accompanied by appropriate bioinformatic algorithms, was evaluated for its performance in GI calculation and was compared with that of a validated next-generation sequencing (NGS) test (myChoice HRD test). In addition, the clinical utility of the GI score (GIS) and BRCA1/2 tumor analysis were investigated in a cohort of 444 patients with ovarian cancer. For that reason, single nucleotide polymorphism (SNP) arrays and appropriate bioinformatics algorithms were used to calculate GIS in 29 patients with ovarian cancer with known GIS status using a validated NGS test. Furthermore, BRCA1/2 analysis results were compared between the aforementioned assay and the amplicon-based Oncomine™ BRCA Research Assay. BRCA1/2 analysis was performed in 444 patients with ovarian cancer, while GIS was calculated in 175 BRCA1/2-negative cases. The bioinformatics algorithm developed for GIS calculation in combination with NGS BRCA1/2 analysis (RediScore), and the OncoscanR pipeline exhibited a high overall agreement with the validated test (93.1%). In addition, the Oncomine NGS assay had a 100% agreement with the validated test. The BRCA1/2 mutation frequency was 26.5% in the examined patients with ovarian cancer. GIS was positive in 40% of the BRCA1/2-negative cases. The RediScore bioinformatics algorithm developed for GIS calculation in combination with NGS BRCA1/2 analysis is a viable and effective approach for HRD calculation in patients with ovarian cancer, offering a positive prediction for PARP inhibitor responsiveness in 55% of the patients.

Upstaging and Downstaging in Gliomas-Clinical Implications for the Fifth Edition of the World Health Organization Classification of Tumors of the Central Nervous System.

In 2021, the 5th edition of the WHO Classification of Tumors of the Central Nervous System (WHO-CNS5) was published as the sixth volume of the international standard for brain and spinal cord tumor classification. The most remarkable practical change in the current classification involves grading gliomas according to molecular characterization. IDH mutant (10%) and IDH wild-type tumors (90%) are two different entities that possess unique biological features and various clinical outcomes regarding treatment response and overall survival. This article presents two comparative cases that highlight the clinical importance of these new classification standards. The first clinical case aimed to provide a comprehensive argument for determining the IDH status in tumors initially appearing as low-grade astrocytoma upon histologic examination, thus underlining the importance of the WHO-CNS5. The second case showed the implications of the histologic overdiagnosis of glioblastoma using the previous classification system with a treatment span of 7 years that proceeded through full-dose re-irradiation up to metronomic therapy. The new WHO-CNS5 classification significantly impacted complex neurooncological cases, thus changing the initial approach to a more precise therapeutic management.

Salvage Surgery for Small-Cell Lung Cancer-A Literature Review.

(1) Background: Salvation surgery for small-cell lung cancer (SCLC) is exceptionally performed, and only a few cases are published. (2) Methods: There are 6 publications that present 17 cases of salvation surgery for SCLC-the salvation surgery was performed in the context of modern clearly established protocols for SCLC and after including SCLC in the TNM (tumor, node, metastasis) staging in 2010. (3) Results: After a median follow-up of 29 months, the estimated overall survival (OS) was 86 months. The median estimated 2-year survival was 92%, and the median estimated 5-year survival was 66%. (4) Conclusion: Salvage surgery for SCLC is a relatively new and extremely uncommon concept and represents an alternative to second-line chemotherapy. It is valuable because it may offer a reasonable treatment for selected patients, good local control, and a favorable survival outcome.

Therapies beyond Physiological Barriers and Drug Resistance: A Pilot Study and Review of the Literature Investigating If Intrathecal Trastuzumab and New Treatment Options Can Improve Oncologic Outcomes in Leptomeningeal Metastases from HER2-Positive Breast Cancer.

Leptomeningeal metastases (LM) are a rare but rapidly fatal complication defined by the spread of tumor cells within the leptomeninges and the subarachnoid space, found in approximately 10% of patients with HER2-positive breast cancers. This pilot study evaluated the efficacy of local treatment with intrathecal Trastuzumab (IT) added to systemic treatment. The oncologic outcome of 14 patients with HER2-positive LM is reported. Seven received IT, and seven received standard of care (SOC). The mean number of IT cycles administered was 12.14 ± 4.00. The response rate to CNS after IT treatment + SOC was 71.4%, and three patients (42.8%) obtained durable responses lasting more than 12 months. The median progression-free survival (mPFS) after LM diagnosis was six months, and the median overall survival (mOS) was ten months. The mean values of the PFS in favor of IT therapy (10.6 mo vs. 6.6 mo) and OS (13.7 vs. 9.3 mo) suggest a non-negligible investigation direction in the sense of exploiting intrathecal administration as a possible treatment modality in these patients. Adverse events reported were local pain related to intrathecal administration and one case of arachnoiditis, hematoma, and CSF fistulae. Intrathecal administration of Trastuzumab, alongside systemic treatment and radiotherapy, might improve oncologic outcomes in LM HER2-positive breast cancer with manageable toxicity.

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.

Oncologic Outcome after Pulmonary Metastasectomy as Part of Multidisciplinary Treatment in a Tertiary Oncological Center.

(1) Background: Pulmonary metastases are encountered in approximately one-third of patients with malignancies, especially from colorectal, lung, breast, and renal cancers, and sarcomas. Pulmonary metastasectomy is the ablative approach of choice, when possible, as part of the multidisciplinary effort to integrate and personalize the oncological treatment. (2) Methods: The study includes 58 consecutive cases of pulmonary metastasectomies, retrospectively analyzed, performed in 12 consecutive months, in which the pathology reports confirmed lung metastases. (3) Results: Most frequent pathological types of metastases were: 14 of colorectal cancer, 10 breast, 8 lung, and 8 sarcomas. At the time of primary cancer diagnosis, 14 patients (24.14%) were in the metastatic stage. The surgical approach was minimally invasive through uniportal VATS (Video-Assisted Thoracic Surgery) in 3/4 of cases (43 patients, 74%). Almost 20% of resections were typical (lobectomy, segmentectomy). Lymphadenectomy was associated in almost 1/2 of patients and lymph node metastases were found in 11.11% of cases. The mortality rate (intraoperative and 90 days postoperative) is zero. The OS after pulmonary metastasectomy is 87% at 18 months, and the estimated OS for cancer is 90% at 5 years. The worst outcome presents the patients with sarcomas and the best outcome-colorectal and lung cancer. The patients with 1 or 2 resected metastases presented 96% survival at 24 months. (4) Conclusions: After pulmonary metastasectomy, survival is favored by the small number of metastases resected (1 or 2), and by the dimension of metastases under 20.5 mm. The non-anatomic (wedge) type of lung resection may present a lower risk of death compared to lobectomy. No statistical significance on survival has the presence of lymphadenectomy, the laterality right/left lung, the upper/lower lobes. In the future, longer follow-up and prospective randomized trials are needed for drawing definitive conclusions.

The Female Reproductive Tract Microbiome and Cancerogenesis: A Review Story of Bacteria, Hormones, and Disease.

The microbiota is the complex community of microorganisms that populate a particular environment in the human body, whereas the microbiome is defined by the entire habitat-microorganisms and their environment. The most abundant and, therefore, the most studied microbiome is that of the gastrointestinal tract. However, the microbiome of the female reproductive tract is an interesting research avenue, and this article explores its role in disease development. The vagina is the reproductive organ that hosts the largest number of bacteria, with a healthy profile represented mainly by Lactobacillus spp. On the other hand, the female upper reproductive tract (uterus, Fallopian tubes, ovaries) contains only a very small number of bacteria. Previously considered sterile, recent studies have shown the presence of a small microbiota here, but there are still debates on whether this is a physiologic or pathologic occurrence. Of particular note is that estrogen levels significantly influence the composition of the microbiota of the female reproductive tract. More and more studies show a link between the microbiome of the female reproductive tract and the development of gynecological cancers. This article reviews some of these findings.

Understanding COVID Vaccination and Its Implication in Cancer Patients' Imaging of Lymph Nodes by PET-CT.

(1) Background: The appearance of enlarged lymph nodes on imaging adds another layer of complexity to the differential diagnosis of disease progression versus immune response to COVID-19 vaccines. Our aim was to find an optimal timing between the vaccination and the PET-CT scan. (2) Methods: 25 cancer patients with 18F-FDG PET-CT evaluations and a history of COVID-19 vaccination between September 2021 and December 2021 were retrospectively analyzed to characterize the lymph nodes related to the time interval from COVID vaccination. (3) Results: All patients presented one or more adenopathies localized in the ipsilateral axilla (96%), ipsilateral cervical area (20%), ipsilateral retropectoral (20%) and pulmonary hilum (8%). The median value of SUVmax was 3.5 ± 0.5. There was a significant indirect correlation between SUVmax and the time passed between the vaccination and the PET CT (Pearson Correlation r = -0.54, p = 0.005). There was no significant difference (p = 0.19) in the SUVmax value in patients receiving Moderna mRNA-1273 vaccine vs. BNT162b2 mRNA Pfizer vaccine. (4) Conclusions: Lymph node enlargement is commonly seen in patients post-vaccination for COVID-19 and must be differentiated from disease progression. The data from our study strongly suggests that the minimum interval of time between an mRNA vaccine and a PET-CT should be more than six weeks.