Meta-analyses reveal serum or plasma Interleukin-6 as a biomarker for malignant ovarian neoplasia.

BACKGROUND: Interleukin-6 (IL-6) has been implicated in various malignancies, including ovarian cancer. However, mixed results have been observed regarding IL-6 levels in different ovarian conditions. This meta-analysis was performed to determine IL-6 levels in the peritoneal fluid and peripheral blood among patients with various adnexal masses. METHODS: Most popular English databases were searched using a predefined search formula. All studies comparing IL-6 levels in plasma, serum or peritoneal fluid of patients with benign tumors, ovarian neoplasms, and healthy controls were included based on inclusion and exclusion criteria. RESULTS: 5953 patients from 22 primary publications raging from 1994 to 2021 were included in the meta-analyses. A pooled IL-6 Mean Difference (MD) of 41 pg/mL for malignant tumors compared to benign ones, with a Confidence Interval (CI) between 19.8 and 62.2, a Z-score of 3.79, and statistical significance with a p = 0.0002 was observed. Pooled results for healthy versus benign ovarian conditions showed an MD of 5.45 pg/mL for serum or plasma IL-6 measurements in favor of benign tumors (CI:0.66-10.25, Z = 2.23 and p = 0.03). The analysis showed an MD for IL-6 levels of 19.59 pg/mL for healthy controls versus malignant ovarian tumors. Peritoneal fluid measurements regarding IL-6's levels showed no significant difference between benign or malignant masses. DISCUSSION/CONCLUSIONS: Higher levels of plasma or serum IL-6 in ovarian neoplasia patients compared to benign conditions or healthy controls identify IL-6 as a discerning factor between benign or malignant ovarian tumors and a potential biomarker for ovarian malignancy.

Baseline Expression of Exosomal miR-92a-3p and miR-221-3p Could Predict the Response to First-Line Chemotherapy and Survival in Metastatic Colorectal Cancer.

The status of predictive biomarkers in metastatic colorectal cancer is currently underdeveloped. Our study aimed to investigate the predictive value of six circulating exosomal miRNAs derived from plasma (miR-92a-3p, miR-143-3p, miR-146a-5p, miR-221-3p, miR-484, and miR-486-5p) for chemosensitivity, resistance patterns, and survival. Thirty-one metastatic colorectal cancer patients were selected before receiving first-line irinotecan- or oxaliplatin-based chemotherapy. Blood samples were harvested at baseline and 4-6 months after the initiation of chemotherapy. The levels of exosomal expression for each miRNA were analyzed by qPCR. Our results for patients receiving first-line FOLFOX showed significantly higher baseline levels of miR-92a-3p (p = 0.007 **), miR-146a-5p (p = 0.036 *), miR-221-3p (p = 0.047 *), and miR-484 (p = 0.009 **) in non-responders (NR) vs. responders (R). Of these, miR-92a-3p (AUC = 0.735), miR-221-3p (AUC = 0.774), and miR-484 (AUC = 0.725) demonstrated a predictive ability to discriminate responses from non-responses, regardless of the therapy used. Moreover, Cox regression analysis indicated that higher expression levels of miR-92a-3p (p = 0.008 **), miR-143-3p (p = 0.009 **), miR-221-3p (p = 0.016 *), and miR-486-5p (p = 0.019 *) at baseline were associated with worse overall survival, while patients expressing higher baseline miR-92a-3p (p = 0.003 **) and miR-486-5p (p = 0.003 **) had lower rates of progression-free survival. No predictive values for candidate microRNAs were found for the post-chemotherapy period. In line with these findings, we conclude that the increased baseline exosomal expression of miR-92a-3p and miR-221-3p seems to predict a lack of response to chemotherapy and lower OS. However, further prospective studies on more patients are needed before drawing practice-changing conclusions.

Cytotoxicity Evaluation of Unmodified Paddlewheel Dirhodium(II,II)-Acetate/-Formamidinate Complexes and Their Axially Modified Low-Valent Metallodendrimers.

Two diphenyl formamidine ligands, four dirhodium(II,II) complexes, and three axially modified low-valent dirhodium(II,II) metallodendrimers were synthesized and evaluated as anticancer agents against the A2780, A2780cis, and OVCAR-3 human ovarian cancer cell lines. The dirhodium(II,II) complexes show moderate cytotoxic activity in the tested tumor cell lines, with acetate and methyl-substituted formamidinate compounds displaying increased cytotoxicity that is relative to cisplatin in the A2780cis cisplatin resistant cell line. Additionally, methyl- and fluoro-substituted formamidinate complexes showed comparable and increased cytotoxic activity in the OVCAR-3 cell line when compared to cisplatin. The low-valent metallodendrimers show some activity, but a general decrease in cytotoxicity was observed when compared to the precursor complexes in all but one case, which is where the more active acetate-derived metallodendrimer showed a lower IC50 value in the OVCAR-3 cell line in comparison with the dirhodium(II,II) tetraacetate.

Current and New Challenges in the Management of Pancreatic Neuroendocrine Tumors: The Role of miRNA-Based Approaches as New Reliable Biomarkers.

Pancreatic neuroendocrine tumors (PanNETs) are rare tumors; however, their incidence greatly increases with age, and they occur more frequently among the elderly. They represent 5% of all pancreatic tumors, and despite the fact that low-grade tumors often have an indolent evolution, they portend a poor prognosis in an advanced stages and undifferentiated tumors. Additionally, functional pancreatic neuroendocrine tumors greatly impact quality of life due to the various clinical syndromes that result from abnormal hormonal secretion. With limited therapeutic and diagnostic options, patient stratification and selection of optimal therapeutic strategies should be the main focus. Modest improvements in the management of pancreatic neuroendocrine tumors have been achieved in the last years. Therefore, it is imperative to find new biomarkers and therapeutic strategies to improve patient survival and quality of life, limiting the disease burden. MicroRNAs (miRNAs) are small endogenous molecules that modulate the expression of thousands of genes and control numerous critical processes involved in tumor development and progression. New data also suggest the implication of miRNAs in treatment resistance and their potential as prognostic or diagnostic biomarkers and therapeutic targets. In this review, we discusses the current and new challenges in the management of PanNETs, including genetic and epigenetic approaches. Furthermore, we summarize the available data on miRNAs as potential prognostic, predictive, or diagnostic biomarkers and discuss their function as future therapeutic targets.

Continuous Intravenous Administration of Granulocyte-Colony-Stimulating Factors-A Breakthrough in the Treatment of Cancer Patients with Febrile Neutropenia.

(1) Background: Febrile neutropenia (FN) remains one of the most challenging problems in medical oncology and is a very severe side effect of chemotherapy. Its late consequences, when it is recurrent or of a severe grade, are dose reduction and therapy delays. Current guidelines allow the administration of granulocyte-colony-stimulating factors (G-CSF) for profound FN (except for the case when a pegylated form of G-CSF is administrated with prophylactic intention) in addition to antibiotics and supportive care. (2) Methods: This is a prospective study that included 96 patients with confirmed malignancy, treated with chemotherapy, who developed FN during their oncological therapy, and were hospitalized. They received standard treatment plus a dose of G-CSF of 16 µg/Kg/day IV continuous infusion. (3) Results: The gender distribution was almost symmetrical: Male patients made up 48.96% and 51.04% were female patients, with no significance on recovery from FN (p = 1.00). The patients who received prophylactic G-CSF made up 20.21%, but this was not a predictive or prognostic factor for the recovery time from aplasia (p = 0.34). The median chemotherapy line where patients with FN were included was two and the number of previous chemotherapy cycles before FN was three. The median serological number of neutrophils (PMN) was 450/mm3 and leucocytes (WBC) 1875/mm3 at the time of FN. Ten patients possess PMN less than 100/mm3. The median time to recovery was 25.5 h for 96 included patients, with one failure in which the patient possessed grade 5 FN. Predictive factors for shorter recovery time were lower levels of C reactive protein (p < 0.001) and procalcitonin (p = 0.002) upon hospital admission and higher WBC (p = 0.006) and PMN (p < 0.001) at the time of the provoking cycle of chemotherapy for FN. The best chance for a shorter duration of FN was a short history of chemotherapy regarding the number of cycles) (p < 0.0001). (4) Conclusions: Continuous IV administration of G-CSF could be an alternative salvage treatment for patients with profound febrile neutropenia, with a very fast recovery time for neutrophiles.

Immediate Breast Reconstruction in Large Ptotic Breasts Using the Inferior Based Dermal Flap. Indications and Technique.

Introduction: Achieving good aesthetic outcomes during immediate reconstruction in women with large ptotic breast presents a unique challenge for the reconstructive surgeon. We present our paradigm regarding immediate reconstruction in patients with large ptotic breasts, using the inferiorly based dermal flap. Materials and Methods: Ten patients with large ptotic breasts underwent mastectomy and immediate implant reconstruction at the "Prof. Dr. I. Chiricuta" Institute of Oncology. The mastectomy was carried out using a Wise pattern skin resection with preservation of a dermal flap at the lower pole of the breast. The flap was sutured to the pectoralis major muscle and completed the subpectoral pocket created for the implant. Results: The reconstruction was done bilaterally in three cases with a total number of 13 reconstructed breasts. Of these 11 required dermal flaps. All reconstructions were completed successfully and there were no implant losses. Four breasts (36%) developed superficial necrosis of the tip of the mastectomy flaps at the T junction. Conclusion: The dermal flap technique is safe, versatile and reliable. It is used in a wide array of reconstructive scenarios as it provides the surgeon with an excellent alternative to more costly and unreliable methods.

Current and New Predictors for Treatment Response in Metastatic Colorectal Cancer. The Role of Circulating miRNAs as Biomarkers.

Colorectal cancer (CRC) is the third most frequently diagnosed cancer in the world. More than half of all CRC patients will eventually develop metastases and require treatment accordingly, but few validated predictive factors for response to systemic treatments exist. In order to ascertain which patients benefit from specific treatments, there is a strong need for new and reliable biomarkers. We conducted a comprehensive search using the PUBMED database, up to December 2019, in order to identify relevant studies on predictive biomarkers for treatment response in metastatic CRC. We will herein present the currently used and potential biomarkers for treatment response and bring up-to-date knowledge on the role of circulating microRNAs, associated with chemotherapy and targeted therapy regimens used in metastatic CRC treatment. Molecular, tumor-related, disease-related, clinical, and laboratory predictive markers for treatment response were identified, mostly proposed, with few validated. Several circulating microRNAs have already proven their role of prediction for treatment response in CRC, but future clinical studies are needed to confirm their role as biomarkers across large cohorts of patients.

Expression of toll-like receptors in ovarian cancer.

PURPOSE: Ovarian cancer continues to be the most lethal gynecologic malignancy, with a complex tumor microenvironment (TME). We investigated the immunohistochemical (IHC) expression of toll like receptors (TLRs) 4,5,7 and 9 together with CD68 and CD 163 as markers for tumor-associated macrophages (TAM) in relation to clinicopathological data. METHODS: Data from 102 patients with serous ovarian cancer treated between 2006 and 2011 was retrospectively reviewed. A TLR IHC score was developed and CD68, CD163 density scores were calculated as the mean number of positive cells from three 0.5 mm2 areas. RESULTS: Advanced-stage disease (FIGO IIIC-IV) was present in 65.7% of cases. A TLR4 score above median was associated with peritoneal carcinomatosis (odds ratio/OR) 3.02, p=0.019) or ascites (OR 2.5, p=0.041). In FIGO stage IIIC-IV patients with a platinum-free interval (PFI) >12 months had, in comparison with patients with PFI ≤12 months, a higher CD68 density score (191.9 ± 95.2 vs. 152.7 ± 69.4, p=0.066) and a lower CD163 density score (106.7 ± 73.3 vs. 154.5 ± 73.9, p=0.011). In early-stage ovarian cancer patients, TLR9 positivity was associated with a higher overall survival than in patients with absent expression (110.2 vs. 22 months, p<0.001), while advanced-stage patients with TLR7 positivity had a lower overall survival than patients with negative TLR7 (38.3 vs. 66.2 months, p=0.01). CONCLUSIONS: Our data shows that TLRs and TAM are important prognostic markers and future studies are needed to better comprehend the immune response in ovarian cancer.

The role of biomarkers and echocardiography in the evaluation of cardiotoxicity risk in children treated for leukemia.

PURPOSE: To describe the high-risk profile group, susceptible to develop anthracycline-induced cardiomyopathy in children with acute leukemia. METHODS: The study involved 35 pediatric patients diagnosed with acute lymphoblastic (ALL) or acute myeloblastic leukemia (AML), from March 2014 to December 2016. Serologic markers used for the analysis of cardiac dysfunction were troponin T, NT-proBNP and PCRhs. Also, the patients have had echocardiographic evaluation at the beginning of treatment to determine LVEF, SF and A, E, E' Doppler waves. RESULTS: Positive linear correlation was shown between NT-proBNP and leukocyte values, NT-proBNP and blast cells value, and NT-proBNP and LDH. Significant linear negative correlations between LVEF with leukocyte values, blast cells values, LDH, SF and leukocyte values, LVEF and NT-proBNP values and LVEF and troponin T values were also identified. A weak negative correlation between E/E' ratio and blast cells values has been observed. All of these correlations were statistically significant (p<0.05). CONCLUSIONS: Leukocyte value, as well as the other serological markers assessed (NT-proBNP, Troponin T), are useful tools to evaluate the risk of anthracycline-induced cardiotoxicity. The variation of the biological markers at the beginning of the cytotoxic treatment confirms the presence of an early myocardial dysfunction, emphasizing the importance of systematic evaluation of this particular group of patients.

Tumor infiltrating lymphocytes as a prognostic factor in malignant melanoma. Review of the literature.

Malignant melanoma represents the major cause of mortality among skin cancers, with increasing incidence and mortality rates worldwide. Despite the numerous public health campaigns and the efforts undertaken in the last decade regarding the establishment of a rapid diagnostic and an efficient treatment for these patients, the long-term prognosis has not been significantly improved. Thus, numerous studies were conducted in order to establish a more accurate prognosis, tumor infiltrating lymphocytes (TILs) being considered in many studies as independent prognostic factors of lymph node metastasis and overall survival in patients with melanoma. Moreover, immunotherapy has been intensively studied and evolved in recent times, and represents a promising treatment option for patients with advanced stage (metastatic) malignant melanoma. In this review article, we provided a literature overview on the histological classification, the history and the essential role of TILs, as well as the implications of regulatory T (Treg) cells and FOX P3 transcription factor in malignant melanoma.

The prognostic role of Skp2 and the tumor suppressor protein p27 in colorectal cancer.

PURPOSE: This study aimed at exploring the role of Skp2, p27 and Cks1 expression as prognostic factors for colorectal cancer (CRC) patients, and to identify a correlation between their expression and the cell proliferation marker Ki67. METHODS: We conducted a retrospective study on 130 patients with CRC treated with surgery and adjuvant treatment at the Oncology Institute Cluj-Napoca between 2006- 2010. The Skp2, p27, Cks1 and Ki67 immunoexpression was grouped from 1 to 4, according to percents of tumor cells with nuclear reactivity. Their correlation with overall survival (OS), recurrence free survival (RFS) and with the classical histopathological prognostic factors were analyzed. All patients had 5-year follow-up. RESULTS: The majority of patients had locally advanced TNM stages II and III. More than a half of the tumors had low immunoexpression of Skp2 and Cks1, and high and moderate p27 and Ki67 expression. Skp2 overexpression negatively influenced the p27 (p=0.002). Both OS and RFS were significantly higher in patients with moderate and high expression of p27 (p=0.005). Skp2 and Cks1 overexpression negatively influenced OS and RFS. Skp2 overexpression positively correlated with TNM stage (p<0.001), node capsular invasion (p=0.002) and lymphovascular invasion (p=0.042). Ki67 expression did not correlate with Skp2 (p=0.88), Cks1 (p=0.67) and p27 (p=0.40), neither with OS (p=0.841) and RFS (p=0.84). CONCLUSIONS: The most important prognostic factor was the Skp2 overexpression. It was the only protein we studied that correlated with the other well-known prognostic factors in CRC. The expression of Ki67 did not bring any novel prognostic information regarding CRC.

Platinum derivatives: a multidisciplinary approach.

Cancer is one of the most difficult diseases to be treated. The particularities regarding the tumors' occurrence mechanism, their evolution under chemotherapy, disease-free interval, but also the increasing number of patients make cancer an intensively studied health domain. Although introduced in therapy since the early 80s, platinum derivatives play an essential role in anticancer therapy. Their use in therapy resulted in improving the patient quality of life and prolonging disease-free interval, which makes them still a benchmark for other anticancer compounds. However, adverse reactions and allergic reactions are a major impediment in therapy with platinum derivatives. This paper summarizes data about platinum derivatives through a multidisciplinary approach, starting from a chemical point of view and on to their mechanism of action, mechanism of cellular resistance, predictive factors for the outcome of chemotherapy such as micro RNAs (miRNAs), tumor suppressor protein p53, and the excision repair cross-complementing 1 protein (ERCC1).

Expression of Nestin and CD133 in serous ovarian carcinoma.

Pupose: Nestin and CD133 are regarded as putative markers of cancer stem cells (CSCs) and related to poor prognosis in various cancer sites. Since few studies have focused on their role in ovarian cancer, we aimed to investigate their predictive value and association with neoangiogenesis. METHODS: Immunohistochemical analysis for nestin and CD133 was performed on 85 serous ovarian carcinoma tumor samples using tissue microarray technique. Nestin immunoreactivity was detected in both tumor and endothelial cells, whilst CD133 was only identified in tumor cells. CD34 endothelial expression was used to assess intratumor microvessel density (MVD). RESULTS: Of the tissue samples 49.4% were nestin-positive and 24.7% were positive for CD133. In both univariate and multivariate analysis nestin or CD133 expressions in tumor cells were not significantly associated with clinicopathological parameters (age, serum CA125, peritoneal carcinomatosis, malignant ascites, tumor grade). However, in multivariate analysis nestin expression in tumor cells proved to be an independent prognostic factor, associated with poorer survival and time to progression (p=0.025 and p=0.05, respectively). This has not been achieved for CD133. Furthermore, a significant concordance between nestin endothelial expression (nestin-determined MVD) and CD34-determined MVD was achieved. CONCLUSION: In addition to the well-known clinicopathological characteristics, tumor expression of nestin might be a valuable prognostic factor for survival in patients with advanced ovarian cancer. With regard to its endothelial expression, nestin might be as reliable as CD34 for quantifying tumor angiogenesis. Further investigation is justified in order to better clarify the role of these biomarkers.

Expression of CDCP1 and ADAM12 in the ovarian cancer microenvironment.

PURPOSE: The tumor microenvironment in ovarian cancer (OC) seems to play an important role, and besides tumor cells, biomarkers can derive from endothelial cells. We investigated CDCP1 and ADAM12 expression in relation with other clinical and pathological characteristics in OC patients. METHODS: We retrospectively evaluated patient files between 2006-2011. A histochemical score was developed to evaluate tumor staining, the microvessel density (MVD), and stromal expression patterns for both ADAM12 and CDCP1. A CD34 antibody was used to assess tumor MVD. RESULTS: 102 patients were selected and 83% had FIGO stage III/IV. A high CDCP1 tumor score correlated significantly with a shorter overall survival (OS) (p<0.01). Cases with positive CDCP1 had an elevated CD34 MVD (p<0.01). An absent/low ADAM12 tumor score correlated with significantly improved OS (p<0.01). Mean CD34 MVD was higher in cases with positive ADAM12 MVD (p=0.012). CONCLUSIONS: Our results indicate that both tumor markers are negative prognostic factors for overall survival and additional studies are required to validate their future potential.

The role of CDCP1 (CUB domain-containing protein 1) and ADAM12 (a disintegrin and metalloproteinase 12) in ovarian cancer.

Ovarian cancer (OC) is the second most common gynecological cancer and the deadliest in industrialized countries, with poor outcomes that indicate an urgent need to provide a greater insight into the molecular mechanisms underlying OC. Insights into the complex tumor microenviroment show that besides tumor islets, OC biomarkers can derive from newly formed blood vessels that have endothelial cells with a different molecular signature in comparison with their normal counterparts. In this view, recent research has been able to highlight promising candidates such as CDCP1 and ADAM12. Our present review summarises their implications in cancer progression with a focus on OC.

Current insights into the association of Nestin with tumor angiogenesis.

Tumor angiogenesis is regarded as a hallmark of cancer and provides an important target for therapy. Nestin is an intermediate filament protein (IF) originally recognized as a neural stem cell marker. Development and progression of cancer requires sustained angiogenesis, dependent on the proliferation and migration of endothelial cells which seem to be better portrayed by nestin expression in various malignancies such as central nervous system, gastro-intestinal cancers, malignant melanoma, lung, prostate or breast cancer. The purpose of the present review was to emphasize the insights into nestin expression in relation to tumor angiogenesis in different types of cancer. Current evidence suggests that nestin positivity in tumor cells reflects stem-like properties of those cells. Whether or not expressed in both tumor and endothelial cells, nestin overexpression might reflect the extent of angiogenesis and function as a molecular anti-angiogenic target for cancer.

Evaluation of clinical, morphopathological and therapeutic prognostic factors in rectal cancer. Experience of a tertiary oncology center.

PURPOSE: Morphopathological factors continue to be the most important prognostic factors in colorectal cancer, but there is evidence regarding the prognostic value of some factors that are not yet used in current clinical practice. The purpose of the present study was to evaluate the most important clinical, morphopathological and therapeutic prognostic factors in rectal cancer. METHODS: This study retrospectively analyzed 317 patients diagnosed and treated at the Ion Chiricuta Institute of Oncology between 2000-2008. The prognostic value of 13 variables was analyzed and correlations between them were established. Nine variables were included in a multivariate analysis model. RESULTS: The 5-year overall survival (OS) was 55.6%, significantly higher for patients with TNM stage I disease 7l.7%), compared to stage II (71.4%), stage III (45.4%) and stage IV (12.5%; p<0.001). In multivariate analysis, the independent prognostic factors were tumor stage, age, lymph node invasion, venous, lymphatic and perineural invasion. CONCLUSIONS: In addition to the TNM stage and lymph node invasion, age, venous, lymphatic and perineural invasion were also proved to have prognostic significance in rectal cancer. Further studies are required for the validation of prognostic assessment models in patients diagnosed with rectal cancer.

The prognostic value of FOXP3+ T regulatory cells in colorectal cancer.

PURPOSE: The evaluation of CD3(+) T-cell density is believed to have a higher prognostic value than the conventionally used TMN stage in colorectal cancer (CRC), but the role of regulatory T lymphocytes (Treg) is still debated. Our study determined the prognostic value of forkhead box P3 nuclear transcription factor (FOXP3) positive Treg and CD3(+) T-cells in the invasive margin of CRC compared with other known prognostic factors. METHODS: The prognostic factors analysed in 42 patients with CRC stage II (N=13) and III (N=29), were age, tumor location, TNM stage, histological grade, vascular, lymphatic and perineural invasion. CD3(+) T-cells and FOXP3(+) Treg density was evaluated by immunohistochemistry. RESULTS: The median CD3(+) T-cells and FOXP3(+) Treg density was 438.93/mm(2) and 162.25/mm(2), respectively. Patients with high FOXP3(+) Treg density showed improved 5-year survival rate of 89.41%, compared with 64.6% of those with low density (p=0.024). CONCLUSIONS: Increased CD3(+) T-cells and FOXP3(+) Treg density is associated with improved survival, but only the latter proved to be an independent prognostic factor. FOXP3(+) Treg infiltrate may play an important prognostic role, which, in combination with other predictive factors, could lead to the development of specific treatment regimens.

Use of Different Anti-PD-1 Checkpoint Combination Strategies for First-Line Advanced NSCLC Treatment-The Experience of Ion Chiricuța Oncology Institute.

PURPOSE: Different combination modalities between an anti-PD-1/PD-L1 agent and a platinum-based chemotherapy or another checkpoint inhibitor (with or without a short course or full course of a platinum doublet) proved superior to chemotherapy alone in multiple clinical trials, but these strategies were not directly compared. The aim of this study is to report the real-world data results with different immunotherapy combinations in a series of patients treated in consecutive cohorts at the Ion Chiricuța Oncology Institute. METHODS: A total of 122 patients were successively enrolled in three cohorts: (1A) nivolumab + ipilimumab (18 patients), (1B) nivolumab + ipilimumab + short-course chemotherapy (33 patients), and (2) pembrolizumab plus full-course chemotherapy (71 patients). Endpoints included overall survival (OS), progression-free survival (PFS), objective response (ORR), and univariate and multivariate exploratory analysis of prognostic factors. RESULTS: Median follow-up in the consecutive cohorts 1A, 1B, and 2 was 83 versus 59 versus 14.2 months. Median OS and PFS for all patients were 22.2 and 11.5 months, respectively, and 2-year actuarial OS and PFS were 49% and 35%, respectively. For the nivolumab + ipilimumab (cohorts 1A and 1B) versus pembrolizumab combinations (cohort 2), median OS was 14 vs. 24.8 months (p = 0.18) and 2-year actuarial survival 42% vs. 53%; median PFS was 8.6 vs. 12.7 months (p = 0.41) and 2-year actuarial PFS 34% vs. 35%; response rates were 33.3% vs. 47.9% (p = 0.22). Older age, impaired PS (2 versus 0-1), corticotherapy in the first month of immunotherapy, and >3.81 neutrophils to lymphocytes ratio were independent unfavorable prognostic factors in the multivariate analysis of survival (limited to 2 years follow-up). The 5-year long-term survival was 30.5% and 18.8% for cohorts 1A and 1B, respectively (not enough follow-up for cohort 2). CONCLUSIONS: Efficacy results using different immunotherapy combination strategies were promising and not significantly different between protocols at 2 years. Real-world efficacy and long-term results in our series were in line with those reported in the corresponding registration trials.

Usefulness of Saline Sealing in Preventing Pneumothorax after CT-Guided Biopsies of the Lung.

This study aimed to assess the effectiveness of saline sealing in reducing the incidence of pneumothorax after a CT-guided lung biopsy. This was a retrospective case-control study of patients who underwent CT-guided biopsies for lung tumors using 18 G semiautomatic core needles in conjunction with 17 G coaxial needles. The patients were divided into two consecutive groups: a historical Group A (n = 111), who did not receive saline sealing, and Group B (n = 87), who received saline sealing. In Group B, NaCl 0.9% was injected through the coaxial needle upon its removal. The incidence of pneumothorax and chest tube insertion was compared between the two groups. Multivariate logistic regression was performed to verify the contribution of other pneumothorax risk factors. The study included 198 patients, with 111 in Group A and 87 in Group B. There was a significantly (p = 0.02) higher pneumothorax rate in Group A (35.1%, n = 39) compared to Group B (20.7%, n = 18). The difference regarding chest tube insertion was not significant (p = 0.1), despite a tendency towards more insertions in Group A (5.4%, n = 6), compared to Group B (1.1%, n = 1). Among the risk factors for pneumothorax, only the presence of emphysema (OR = 3.5, p = 0.0007) and belonging to Group A (OR = 2.2, p = 0.02) were significant. Saline sealing of the needle tract after a CT-guided lung biopsy can significantly reduce the incidence of pneumothorax. This technique is safe, readily available, and inexpensive, and should be considered as a routine preventive measure during this procedure.