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.

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.

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.

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.

The Benefits and Challenges of the Multimodal Treatment in Advanced/Metastatic Malignant Melanoma.

Currently, the treatment of malignant melanoma offers the longest and the most studied experience of innovative treatments in malignant pathology. The algorithm of the therapeutic decision in advanced or metastatic melanoma must comprise: the timing of the therapeutic initiation, the sequencing of the specific oncological treatment (radiotherapy and chemotherapy still being therapeutic alternatives in selected cases), the diagnosis and the management of adverse reactions. We present the case of a patient diagnosed with metastatic malignant melanoma in November 2019, who progressed successively under new systemic treatment throughout the 3 years of treatment and experienced skin reactions of various degrees of severity. The comprehensive response to secondary hilar pulmonary lymphatic determinations under subsequent chemotherapy was specific to the presented case. The occurrence of vitiligo secondary to immunotherapy is a favorable prognostic factor, but the occurrence of secondary cerebral determinations is an extremely severe prognostic factor in malignant melanoma and a challenge in making the therapeutic decision. Previous treatment with immune checkpoint inhibitors may trigger a favorable response to systemic chemotherapy. The early and accurate diagnosis of the adverse events of the new therapies requires a multidisciplinary approach, because it can radically change the therapeutic decision.

Eosinophilic, polymorphic, and pruritic eruption associated with radiation therapy in two patients diagnosed with prostate cancer.

Key Clinical Message: We report 2 cases of EPPER diagnosed in patients who received radiation therapy and hormonal therapy for locally advanced prostate cancer. Both our patients developed this rare late toxicity, but early diagnosis and treatment of this adverse event offers a good prognosis, with no unnecessary interruptions of oncological treatment required. Abstract: Acute and late adverse events are a major problem for patients receiving radiation therapy. We describe two cases of eosinophilic, polymorphic, and pruritic eruption associated with radiotherapy (EPPER) syndrome, a very uncommon toxicity that affects cancer patients. Both our cases were men diagnosed with localized prostate cancer and were treated with radiotherapy and hormonal therapy. They developed EPPER during and after completing the total radiation dose. Multiple tests and skin biopsies were performed in order to find a superficial perivascular lymphohistiocytic infiltrate, confirming EPPER. The patients received corticotherapy and fully recovered after this treatment. There are a few more cases of EPPER reported in the literature, but the pathogenic mechanism is still unknown. EPPER is an important side effect of radiation therapy and it is probably underdiagnosed, due to its occurrence (usually after completing the oncological treatment).

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.

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.

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.

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.

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.

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.

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.

Standardized Uptake Values on SPECT/CT: A Promising Alternative Tool for Treatment Evaluation and Prognosis of Metastatic Neuroendocrine Tumours.

(1) Background: The aim of our study was to assess the feasibility of 99mTcEDDA/HYNIC-TOC SPECT/CT quantitative analysis in evaluating treatment response and disease progression in patients with NETs. (2) Methods: This prospective monocentric study evaluated 35 SPECT/CT examinations performed on 14 patients with neuroendocrine tumours who underwent a baseline and at least one follow-up 99mTcEDDA/HYNIC-TOC scan as part of their clinical management. The examination protocol included a whole-body scan acquired 2 h after the radiotracer's administration, with the SPECT/CT performed 4 h post-injection. Images were analyzed by two experienced physicians and patients were classified into response categories based on their changes in SUV values. (3) Results: We evaluated 14 baseline studies and 21 follow-up scans, accounting for 123 lesions. A statistically positive correlation has been found between the SUVmax and SUVpeak values in tumoral lesions (p < 0.05). No correlation has been found between the SUV values and the ki67 proliferation index. Finally, 64.29% patients were classified as SD at the end of the study, with only 14.29% of patients exhibiting PD and 21.43% patients with PR. (4) Conclusions: The quantitative analysis of 99mTcEDDA/HYNIC-TOC SPECT/CT data in patients with neuroendocrine tumours could represent an alternative to 68Ga-DOTA-peptides PET/CT for the monitoring and prognosis of NETs.

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.

Aspects Regarding the Influence of Obesity on the Molecular Characteristics of Breast Tumors.

The influence of excess adipose tissue on the evolution and prognosis of breast cancer has been evaluated in numerous papers over the years. The ways in which obesity can influence the development, progression, and prognosis of this neoplasia are complex and requires the design of new studies, both clinical and preclinical. The aim of this study is to highlight a possible correlation between obesity-specific tumor microenvironment markers (adipokine or leptin) and the different histological subtypes and aggressive characteristics of breast tumors. We prospectively monitored the prognostic values of 39 patients diagnosed with breast cancer who received oncologic-specific treatment or are in follow-up regarding some obesity markers. Our analysis included parameters such as age, body mass index, immunohistochemical characteristics, and plasma concentration of leptin. The methodology was designed to reveal a possible correlation between obesity (quantified by measuring body mass index and waist circumference), the plasma level of leptin, and breast tumor immunohistochemical characteristics. The patients diagnosed with aggressive tumors subtypes (HER2-positive and triple-negative) had a significantly higher body mass index than patients diagnosed with luminal type tumors (32 kg/sqm versus 27 kg/sqm), the difference being 5 kg/sqm. In patients with non-luminal type breast tumors (HER2-positive and triple-negative), serum concentration of leptin is 55 pg/ml compared to 48 pg/ml in luminal type, statistically significant, p=0.0168. Leptin plays an important role in the connection of specific microenvironment tumors to breast cancer. An increased serum concentration of this adipokine was found in patients with HER2-positive and triple-negative breast tumors compared with luminal-type breast tumors, which could open new directions in the research of breast cancer prognosis in obese patients.

Is There a Role for Minimally Invasive Surgery in Cervical Cancer Treatment: Carry on, Discard, or Modify? A Literature Review and Case Series Presentation.

Oncological surgery is constantly evolving. Recommendations and guidelines are updated periodically in light of new research. Since surgery is a key step in the treatment of cervical cancer in Romania and considering the new findings, this study aims to assess the new guideline recommendations and the surgical treatment options available. The paradigm shift that took place in 2018 left the question: does minimally invasive surgery still play a role in the treatment of cervical cancer? K ouml;hler surgical technique seems to address some of the issues raised by the minimally invasive surgery with good results. H ouml;ckel proposes total mesometrial excision to decrease the risk of recurrence. This study presents 3 cases of cervical cancer patients with stages ranging from IB1 to IIIB that had undergone total mesometrial excision and vaginal cuff closure using the laparoscopic approach to minimize the risk of local recurrence. The case series presented showed that it is feasible and safe to merge these techniques. Further prospective studies are needed in order to assess the risk and benefits of these techniques.

Final Safety and Health-Related Quality of LIfe Results of the Phase 2/3 Act.In.Sarc Study With Preoperative NBTXR3 Plus Radiation Therapy Versus Radiation Therapy in Locally Advanced Soft-Tissue Sarcoma.

PURPOSE: Act.In.Sarc (NCT02379845) demonstrated that the first-in-class radioenhancer NBTXR3, activated by preoperative radiation therapy (RT), doubled the rate of pathologic complete response after resection compared with preoperative RT alone in adult patients with locally advanced soft tissue sarcoma of the extremity or trunk wall (16.1% vs 7.9%, P = .045), and more patients achieved R0 resections (77.0% vs 64.0%, P = .042). These are the toxicity and health-related quality of life (HRQoL) results. METHODS AND MATERIALS: Act.In.Sarc randomized eligible patients 1:1 to either NBTXR3 (single intratumoral injection, volume equivalent to 10% of baseline tumor volume, at 53.3 g/L) activated by external-beam RT (arm A) or external-beam RT alone (arm B) (50 Gy in 25 fractions), followed by surgery in both arms. Here, we report the safety analyses in the all-treated population with a long-term follow-up of at least 2 years, and HRQoL in the intention-to-treat full analysis set. RESULTS: During the on-treatment period, serious adverse events (SAEs) of all grades related to NBTXR3 occurred in 10.1% (9/89) of patients (arm A), and SAEs related to RT occurred in 5.6% (5/89) (arm A) versus 5.6% (5/90) (arm B); postsurgery hospitalization owing to SAEs occurred in 15.7% (14/89) (arm A) versus 24.4% (22/90) (arm B). During the follow-up period, posttreatment SAEs (regardless of relationship) occurred in 13.5% (12/89) (arm A) versus 24.4% (22/90) (arm B). NBTXR3 did not negatively affect HRQoL; during the follow-up period, there was an improvement in most mean Toronto extremity salvage, EuroQoL 5-dimension (EQ-5D), EQ5D02-EQ visual analog scale, reintegration to normal living index, and musculoskeletal tumor rating scale scores. CONCLUSIONS: NBTXR3 did not negatively affect safety or HRQoL. Long-term safety results reinforce the favorable benefit-risk ratio of NBTXR3 plus RT.

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.