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.

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.

Management of Epicardial Metastasis in Breast Cancer.

Background: Cardiac metastasis may be encountered more frequently than primary cardiac tumors. They are discovered at autopsies with an incidence between 1.5 - 20%. The primary tumors that generate cardiac metastasis are malignant melanomas, lymphoma, the lungs, the breast, the esophagus. The organ most affected is the pericardium (62-81%). In 90% of cases from a clinical point of view, they are generally silent. In the case of patients diagnosed with breast cancer and who have undergone radiotherapy, differential diagnosis with fibrosis post radiotherapy interferes. The treatment is palliative and should be administered according to the primary location of the tumor and the patient's performance status. Case presentation: We are presenting the case of a 73-year-old diagnosed and treated for a breast neoplasm in the left breast in 2006. After a period of time of 9 years, the patient presents secondary sternal bone determination, radio-treated and for which she once again goes under hormonal therapy. In 2018, patient performed an imaging evaluation that revealed lung metastases. At the moment of stage review, performed in 2020, secondary epicardial determinations are noted. We present the case, the therapeutic management, diagnostic procedures and treatment and also, we discuss the data from literature. Conclusion: Cardiac metastases are rare and and in most cases are silent. The incidence has changed due to treatment options and imaging investigations. Stereotactic body radiation therapy can be considereda a therapeutic option in the cases with good performance status and with oligometastatic disease.

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.

NBTXR3, a first-in-class radioenhancer hafnium oxide nanoparticle, plus radiotherapy versus radiotherapy alone in patients with locally advanced soft-tissue sarcoma (Act.In.Sarc): a multicentre, phase 2-3, randomised, controlled trial.

BACKGROUND: Pathological complete response to preoperative treatment in adults with soft-tissue sarcoma can be achieved in only a few patients receiving radiotherapy. This phase 2-3 trial evaluated the safety and efficacy of the hafnium oxide (HfO2) nanoparticle NBTXR3 activated by radiotherapy versus radiotherapy alone as a pre-operative treatment in patients with locally advanced soft-tissue sarcoma. METHODS: Act.In.Sarc is a phase 2-3 randomised, multicentre, international trial. Adults (aged ≥18 years) with locally advanced soft-tissue sarcoma of the extremity or trunk wall, of any histological grade, and requiring preoperative radiotherapy were included. Patients had to have a WHO performance status of 0-2 and a life expectancy of at least 6 months. Patients were randomly assigned (1:1) by an interactive web response system to receive either NBTXR3 (volume corresponding to 10% of baseline tumour volume at a fixed concentration of 53·3 g/L) as a single intratumoural administration before preoperative external-beam radiotherapy (50 Gy in 25 fractions) or radiotherapy alone, followed by surgery. Randomisation was stratified by histological subtype (myxoid liposarcoma vs others). This was an open-label study. The primary endpoint was the proportion of patients with a pathological complete response, assessed by a central pathology review board following European Organisation for Research and Treatment of Cancer guidelines in the intention-to-treat population full analysis set. Safety analyses were done in all patients who received at least one puncture and injection of NBTXR3 or at least one dose of radiotherapy. This study is registered with ClinicalTrials.gov, number NCT02379845, and is ongoing for long-term follow-up, but recruitment is complete. FINDINGS: Between March 3, 2015, and Nov 21, 2017, 180 eligible patients were enrolled and randomly assigned and 179 started treatment: 89 in the NBTXR3 plus radiotherapy group and 90 in the radiotherapy alone group. Two patients in the NBTXR3 group and one patient in the radiotherapy group were excluded from the efficacy analysis because they were subsequently discovered to be ineligible; thus, a total of 176 patients were analysed for the primary endpoint in the intention-to-treat full analysis set (87 in the NBTXR3 group and 89 in the radiotherapy alone group). A pathological complete response was noted in 14 (16%) of 87 patients in the NBTXR3 group and seven (8%) of 89 in the radiotherapy alone group (p=0·044). In both treatment groups, the most common grade 3-4 treatment-emergent adverse event was postoperative wound complication (eight [9%] of 89 patients in the NBTXR3 group and eight [9%] of 90 in the radiotherapy alone group). The most common grade 3-4 adverse events related to NBTXR3 administration were injection site pain (four [4%] of 89) and hypotension (four [4%]) and the most common grade 3-4 radiotherapy-related adverse event was radiation skin injury in both groups (five [6%] of 89 in the NBTXR3 group and four [4%] of 90 in the radiotherapy alone group). The most common treatment-emergent grade 3-4 adverse event related to NBTXR3 was hypotension (six [7%] of 89 patients). Serious adverse events were observed in 35 (39%) of 89 patients in the NBTXR3 group and 27 (30%) of 90 patients in the radiotherapy alone group. No treatment-related deaths occurred. INTERPRETATION: This trial validates the mode of action of this new class of radioenhancer, which potentially opens a large field of clinical applications in soft-tissue sarcoma and possibly other cancers. FUNDING: Nanobiotix SA.

A Randomized Phase II Trial (TAMIGA) Evaluating the Efficacy and Safety of Continuous Bevacizumab Through Multiple Lines of Treatment for Recurrent Glioblastoma.

BACKGROUND: We assessed the efficacy and safety of bevacizumab (BEV) through multiple lines in patients with recurrent glioblastoma who had progressed after first-line treatment with radiotherapy, temozolomide, and BEV. PATIENTS AND METHODS: TAMIGA (NCT01860638) was a phase II, randomized, double-blind, placebo-controlled, multicenter trial in adult patients with glioblastoma. Following surgery, patients with newly diagnosed glioblastoma received first-line treatment consisting of radiotherapy plus temozolomide and BEV, followed by six cycles of temozolomide and BEV, then BEV monotherapy until disease progression (PD1). Randomization occurred at PD1 (second line), and patients received lomustine (CCNU) plus BEV (CCNU + BEV) or CCNU plus placebo (CCNU + placebo) until further disease progression (PD2). At PD2 (third line), patients continued BEV or placebo with chemotherapy (investigator's choice). The primary endpoint was survival from randomization. Secondary endpoints were progression-free survival in the second and third lines (PFS2 and PFS3) and safety. RESULTS: Of the 296 patients enrolled, 123 were randomized at PD1 (CCNU + BEV, n = 61; CCNU + placebo, n = 62). The study was terminated prematurely because of the high drop-out rate during first-line treatment, implying underpowered inferential testing. The proportion of patients receiving corticosteroids at randomization was similar (BEV 33%, placebo 31%). For the CCNU + BEV and CCNU + placebo groups, respectively, median survival from randomization was 6.4 versus 5.5 months (stratified hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.69-1.59), median PFS2 was 2.3 versus 1.8 months (stratified HR, 0.70; 95% CI, 0.48-1.00), median PFS3 was 2.0 versus 2.2 months (stratified HR, 0.70; 95% CI, 0.37-1.33), and median time from randomization to a deterioration in health-related quality of life was 1.4 versus 1.3 months (stratified HR, 0.76; 95% CI, 0.52-1.12). The incidence of treatment-related grade 3 to 4 adverse events was 19% (CCNU + BEV) versus 15% (CCNU + placebo). CONCLUSION: There was no survival benefit and no detriment observed with continuing BEV through multiple lines in patients with recurrent glioblastoma. IMPLICATIONS FOR PRACTICE: Previous research suggested that there may be value in continuing bevacizumab (BEV) beyond progression through multiple lines of therapy. No survival benefit was observed with the use of BEV through multiple lines in patients with glioblastoma who had progressed after first-line treatment (radiotherapy + temozolomide + BEV). No new safety concerns arose from the use of BEV through multiple lines of therapy.

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.

Bevacizumab plus paclitaxel versus bevacizumab plus capecitabine as first-line treatment for HER2-negative metastatic breast cancer (TURANDOT): primary endpoint results of a randomised, open-label, non-inferiority, phase 3 trial.

BACKGROUND: The randomised phase 3 TURANDOT trial compared two approved bevacizumab-containing regimens for HER2-negative metastatic breast cancer in terms of efficacy, safety, and quality of life. The interim analysis did not confirm non-inferior overall survival (stratified hazard ratio [HR] 1·04; 97·5% repeated CI [RCI] -∞ to 1·69). Here we report final results of our study aiming to show non-inferior overall survival with first-line bevacizumab plus capecitabine versus bevacizumab plus paclitaxel for locally recurrent or metastatic breast cancer. METHODS: In this multinational, open-label, randomised phase 3 TURANDOT trial, patients aged 18 years or older who had an Eastern Cooperative Oncology Group performance status 0-2 and measurable or non-measurable HER2-negative locally recurrent or metastatic breast cancer who had received no previous chemotherapy for locally recurrent or metastatic breast cancer were stratified and randomly assigned (1:1) using permuted blocks of size six to either bevacizumab plus paclitaxel (bevacizumab 10 mg/kg on days 1 and 15 plus paclitaxel 90 mg/m(2) on days 1, 8, and 15 every 4 weeks) or bevacizumab plus capecitabine (bevacizumab 15 mg/kg on day 1 plus capecitabine 1000 mg/m(2) twice daily on days 1-14 every 3 weeks) until disease progression, unacceptable toxicity, or withdrawal of consent. Stratification factors were oestrogen or progesterone receptor status, country, and menopausal status. The primary objective was to show non-inferior overall survival with bevacizumab plus capecitabine versus bevacizumab plus paclitaxel in the per-protocol population by rejecting the null hypothesis of inferiority (HR ≥1·33) using a stratified Cox proportional hazard model. This trial is registered with ClinicalTrials.gov, number NCT00600340. FINDINGS: Between Sept 10, 2008, and Aug 30, 2010, 564 patients were randomised, representing the intent-to-treat population. The per-protocol population comprised 531 patients (266 in the bevacizumab plus paclitaxel group and 265 in the bevacizumab plus capecitabine group). At the final overall survival analysis after 183 deaths (69%) in 266 patients receiving bevacizumab plus paclitaxel and 201 (76%) in 265 receiving bevacizumab plus capecitabine in the per-protocol population, median overall survival was 30·2 months (95% CI 25·6-32·6 months) versus 26·1 months (22·3-29·0), respectively. The stratified HR was 1·02 (97·5% RCI -∞ to 1·26; repeated p=0·0070), indicating non-inferiority. The unstratified Cox model (HR 1·13 [97·5% RCI -∞ to 1·39]; repeated p=0·061) did not support the primary analysis. Intent-to-treat analyses were consistent with the per-protocol results. The most common grade 3 or worse adverse events were neutropenia (54 [19%] of 284 patients in the bevacizumab plus paclitaxel group vs 5 [2%] of 277 patients in the bevacizumab plus capecitabine group), hand-foot syndrome (1 [<1%] vs 43 [16%]), peripheral neuropathy (39 [14%] vs 1 [<1%]), leucopenia (20 [7%] vs 1 [<1%]), and hypertension (12 [4%] vs 16 [6%]). Serious adverse events were reported in 65 (23%) of 284 patients receiving bevacizumab plus paclitaxel and 68 (25%) of 277 receiving bevacizumab plus capecitabine. Deaths in two (1%) of 284 patients in the bevacizumab plus paclitaxel group were deemed by the investigator to be treatment-related. No treatment-related deaths occurred in the bevacizumab plus capecitabine group. INTERPRETATION: Bevacizumab plus capecitabine represents a valid first-line treatment option for HER2-negative locally recurrent or metastatic breast cancer, offering good tolerability without compromising overall survival compared with bevacizumab plus paclitaxel. Although progression-free survival with the bevacizumab plus capecitabine combination is inferior to that noted with bevacizumab plus paclitaxel, we suggest that physicians should consider possible predictive risk factors for overall survival, individual's treatment priorities, and the differing safety profiles. FUNDING: Roche.

Predictive role of hand-foot syndrome in patients receiving first-line capecitabine plus bevacizumab for HER2-negative metastatic breast cancer.

BACKGROUND: Correlations between development of hand-foot syndrome (HFS) and efficacy in patients receiving capecitabine (CAP)-containing therapy are reported in the literature. We explored the relationship between HFS and efficacy in patients receiving CAP plus bevacizumab (BEV) in the TURANDOT randomised phase III trial. METHODS: Patients with HER2-negative locally recurrent/metastatic breast cancer (LR/mBC) who had received no prior chemotherapy for LR/mBC were randomised to BEV plus paclitaxel or BEV-CAP until disease progression or unacceptable toxicity. This analysis included patients randomised to BEV-CAP who received ⩾1 CAP dose. Potential associations between HFS and both overall survival (OS; primary end point) and progression-free survival (PFS; secondary end point) were explored using Cox proportional hazards analyses with HFS as a time-dependent covariate (to avoid overestimating the effect of HFS on efficacy). Landmark analyses were also performed. RESULTS: Among 277 patients treated with BEV-CAP, 154 (56%) developed HFS. In multivariate analyses, risk of progression or death was reduced by 44% after the occurrence of HFS; risk of death was reduced by 56%. The magnitude of effect on OS increased with increasing HFS grade. In patients developing HFS within the first 3 months, median PFS from the 3-month landmark was 10.0 months vs 6.2 months in patients without HFS. Two-year OS rates were 63% and 44%, respectively. CONCLUSIONS: This exploratory analysis indicates that HFS occurrence is a strong predictor of prolonged PFS and OS in patients receiving BEV-CAP for LR/mBC. Early appearance of HFS may help motivate patients to continue therapy.

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.

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).

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.

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.

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.

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.

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.