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Purpose: The aim of the study was to determine outcomes after heart transplantation for cytomegalovirus (CMV) mismatched patients (D+/R−) who underwent a surveillance and preemptive therapy protocol, compared to nonmismatch patients. Methods: A review of patient records from January 2010 to December 2020 with follow‐up to October 2023 was done. The protocol consisted weekly surveillance with CMV PCR starting 4 weeks after transplant continuing up until the patient seroconverts or up to 3 months posttransplant if the patient does not seroconvert. Valganciclovir was given for 2 weeks to those who seroconverted. Results: Two hundred and twenty‐one patients were included, and 23% were mismatched patients. Overall survival was not different between CMV groups (p = NS). Causes of death and morbidities were also not significantly different (p = NS). Sixty‐six percent of mismatch patients seroconverted, and there was also a significantly older donor age in the seroconverted patients compared to nonseroconverted patients (41 ± 11 vs. 29 ± 12 years, p < 0.005), indicating a higher risk donor profile. A multivariate Cox regression including donor age showed that there was no increase in mortality in the seroconverted mismatches compared to nonmismatch patients (p = NS). Conclusions: There is no significant increased mortality or morbidity using a CMV surveillance and preemptive therapy protocol. The effect of donor age on seroconversion of mismatches requires further validation. [ABSTRACT FROM AUTHOR]

Objectives: Pharmacological and non‐pharmacological interventions are mostly designed for patients with early Alzheimer's disease (AD) dementia. Long‐term case management and planning for the remainder of life with disability require an estimation of the survival duration. Methods: This cohort study utilized data from the National Health Insurance Research Database, Taiwan, to identify incident cases of mild‐to‐moderate AD dementia diagnosed from 2000 to 2002, followed through December 31, 2017. A multivariate Cox proportional hazards regression model was constructed to compare the independent effects of age, sex, and comorbidities on all‐cause mortality risk. Cumulative survival rates and survival times were estimated. Results: A total of 5258 incident cases were identified, all treated with cholinesterase inhibitors after diagnosis confirmation by an expert committee. During the 15‐year follow‐up period, 4331 deaths occurred. The 1‐, 3‐, 5‐, 10‐, and 15‐year cumulative survival rates were 95, 92, 67, 37, and 18, respectively. The median (95% CI) survival time after diagnosis was 7.69 (7.46–7.90) years overall, 6.37 (6.06–6.65) years in men, and 8.81 (8.49–9.12) years in women. After stratification by age and number of comorbidities, the median survival time ranged from 13.72 (ages 40–64) to 5.29 (ages ≥ 80) years among those without comorbidities. For those with ≥ 3 comorbidities, the median survival times decreased to 6.43 for individuals diagnosed at ages 40–64 and to 2.98 years for those diagnosed at age 80 or older. Conclusions: This nationwide, large, long‐term cohort study provided survival rates and durations from diagnosis to death, varying by sex, age group, and presence/number of comorbidities. This information can serve as a foundation for further cost‐effectiveness studies on new treatments, and may aid clinicians, patients, and families in shared decision‐making and advance personalized care planning for early dementia cases. [ABSTRACT FROM AUTHOR]

Objective: The primary treatment for stage I non-small cell lung cancer (NSCLC) in medically inoperable patients is stereotactic body radiation therapy (SBRT). The current study aimed to retrospectively analyze patients who underwent SBRT. Methods: A total of 188 patients with stage I NSCLC treated with SBRT between 2014 and 2020 were enrolled. Local control (LC), progressionfree survival (PFS), overall survival (OS), and treatment-related toxicities were analyzed. Results: Patients were mostly male (65.7%, n=71), with a median age of 68 (56-88). Based on tumor size and location, 69 patients (63.9%) received between 50 and 60 Gy in 5 fractions, 26 patients (24.1%) received 54 Gy in 3 fractions, 11 patients (10.2%) received 60 Gy in 8 fractions, and 2 patients (1.8%) received 60 Gy in 3 fractions. The median follow-up time was 32 months (12-47 months). Locoregional relapse occurred in 11 patients, among whom 4 (3.7%) developed distant metastasis. The 3-year LC, OS, and PFS rates were 89.5%, 83%, and 72%, respectively. Advanced age and presence of chronic obstructive pulmonary disease were associated with a decreased 3-year OS. In smokers and those with large tumor volumes, PFS decreased to 3 years. No grade 3 or 4 treatment-related toxicities were observed. Conclusion: SBRT is a fast, safe, and valuable therapeutic approach for patients with early-stage medically inoperable NSCLC, providing significant tumor control rates with low toxicity. [ABSTRACT FROM AUTHOR]

Purpose: Peptide receptor radionuclide therapy (PRRT) is a targeted molecular therapy used to treat neuroendocrine tumours (NETs). It has been shown to be effective and well tolerated in patients with metastatic NETs in several centres in the USA, Europe, and Australia. Tolerability and efficacy data emerging from Asian centres remain few. Epidemiological evidence suggests that there are differences in neuroendocrine neoplasms between the population groups. We aim to describe the treatment and safety outcomes of PRRT in the Asian population. Methods: One hundred and seven (107) patients with metastatic NETs who had undergone PRRT treatment from January 2012 to March 2019 were included in this retrospective study. The response rates using RECIST 1.1 and qualitative analysis were examined. The overall and progression-free survival curves were also evaluated. Results: The median progression-free survival was 49 months. Response assessment after completion of treatment showed that 33 (37.9%) of 87 patients had partial or complete response. Subgroup analysis comparing high- and low-grade NET showed that there was a significant difference in the time to progression curves. Comparison of the number of cycles and progression-free and overall survival also showed a significant difference. Ten patients (9%) had grade 3 or more haematological toxicities. Four patients (4%) had grade 3/4 hepatobiliary toxicities, although the presence of extensive liver metastases was a confounding factor. None of the patients had grade 3/4 acute kidney injury. Conclusion: Our results show that PRRT is safe and effective in the treatment of metastatic NET in the Asian population. There was a significant difference in the progression-free survival curves between low-grade and high-grade NET and in the progression-free and overall survival comparing the number of cycles received. [ABSTRACT FROM AUTHOR]

Introduction: Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumours that produce catecholamines. [131I] metaiodobenzylguanidine (MIBG)-avid unresectable or metastatic PPGLs are treated with [131I] MIBG radionuclide therapy. A high metabolic tumour volume (MTV) and total lesion glycolysis (TLG) can be poor prognostic factors. Therefore, we evaluated the metabolic responses to [131I] MIBG therapy with respect to other clinical factors. Methods: A retrospective study was performed on a series of 20 patients who underwent FDG-PET before and after [131I] MIBG therapy. We administered a single dose comprising 5.5 GBq of [131I] MIBG (usually three times; for some cases, the number was increased or decreased considering treatment efficacy and side effects). Semi-quantitative parameters (SUVmax, MTV, and TLG) were calculated using the liver SUV (mean + 3 × standard deviation) as a threshold on Metavol software. The semi-quantitative FDG-PET parameters for determining response were complete response (CR), partial remission (PR), stable disease (SD), and progressive disease (PD). We divided our study participants into the PD and non-PD groups (i.e., SD + PR + CR) and compared the overall survival (OS) between the two groups. Subsequently, we evaluated the relationships between metabolic response and age, sex, tumour type, metastatic site, chemotherapy or external radiation history, and 24-h urine catecholamine levels by univariate logistic regression analyses. Results: Both MTV-based and TLG-based criteria for PD versus non-PD were significant prognostic factors (p = 0.014). However, treatment response as evaluated based on the SUVmax was not a significant predictor. Higher urinary dopamine levels were associated with poor metabolic response as assessed by MTV and TLG (OR 1.002, p = 0.029). The other clinical parameters were non-significant. Conclusion: Poor metabolic response (measured with MTV and TLG) to [131I] MIBG therapy in unresectable or metastatic PPGLs was related to shorter OS. The poor metabolic response can be predicted using the urinary dopamine level. [ABSTRACT FROM AUTHOR]

Objective: To explore the survival effect of thoracic gross tumor volume (GTV) in three‐dimensional (3D) radiotherapy for stage IV non‐small cell lung cancer (NSCLC). Methods: The data cases were obtained from a single‐center retrospective analysis. From May. From 2008 to August 2018, 377 treatment criteria were enrolled. GTV was defined as the volume of the primary lesion and the hilus as well as the mediastinal metastatic lymph node. Chemotherapy was a platinum‐based combined regimen of two drugs. The number of median chemotherapy cycles was 4 (2–6), and the cut‐off value of the planning target volume (PTV) dose of the primary tumor was 63 Gy (30–76.5 Gy). The cut‐off value of GTV volume was 150 cm3 (5.83–3535.20 cm3). Results: The survival rate of patients with GTV <150 cm3 is better than patients with GTV ≥150 cm3. Multivariate Cox regression analyses suggested that peripheral lung cancer, radiation dose ≥63 Gy, GTV <150 cm3, 4–6 cycles of chemotherapy, and CR + PR are good prognostic factors for patients with stage IV non‐small cell lung cancer. The survival rate of patients with GTV <150 cm3 was longer than patients with ≥150 cm3 when they underwent 2 to 3 cycles of chemotherapy concurrent 3D radiotherapy (p < 0.05). When performing 4 to 6 cycles of chemotherapy concurrent 3D radiotherapy, there was no significant difference between <150 cm3 and ≥150 cm3. Conclusions: The volume of stage IV NSCLC primary tumor can affect the survival of patients. Appropriate treatment methods can be opted by considering the volume of tumors to extend patients' lifetime to the utmost. [ABSTRACT FROM AUTHOR]

Background: Tumor cells (TC) participate in tumor progression by altering the immune responses in the tumor microenvironment. However, the clinical relevance and prognostic effect of PD‐L1 expression and tumor‐infiltrating lymphocytes (TILs) in esophageal squamous cell carcinoma (ESCC) are unknown. The purpose of this study was to investigate the interactions and clinical significance of PD‐L1 expression and TILs in ESCC. Methods: Tissue specimens were collected from 126 patients with ESCC who underwent curative esophagectomy. Immunohistochemical analysis and multiplex immunofluorescence for CD4, CD8, CD25, FOXP3, and PD‐L1 in the tumor were used to identify multiple tumor‐infiltrating immune cells (TIIC), Tregs, and TC. Results: PD‐L1 was expressed in tumor cells (PD‐L1 TC). PD‐L1 TIIC and PD‐L1 TC affected the biological behavior of TC. The positive expression rate of PD‐L1 TC and CD8+ TILs was 27.8% (35/126) and 31.7% (40/126), respectively. Kaplan–Meier analysis showed that overall survival (OS) was significantly associated with decreased CD8+ TILs and PD‐L1 TC‐positive expression, which promote ESCC progression and metastasis. Conclusion: Tumor depth, CD8, and PD‐L1 TC were independent prognostic factors in ESCC, and a predictive nomogram with these three risk factors improved the accuracy of predicting OS in patients with ESCC after surgical resection. The conjoint analysis of multiple immune‐related factors is beneficial for stratifying patient survival risk. [ABSTRACT FROM AUTHOR]

Background: The therapeutic advantage of thoracic radiotherapy (tRT) as an adjunct to first‐line immunotherapy and chemotherapy in patients with extensive‐stage small cell lung cancer (ES‐SCLC) remains unclear. We sought to elucidate this in a retrospective cohort study comparing the effectiveness and safety of tRT in combination with first‐line immunotherapy and chemotherapy. Methods: Our retrospective study included patients with ES‐SCLC, treated at the West China Hospital between January 2019 and December 2022. They received first‐line immunotherapy and chemotherapy and were categorized into two cohorts based on the administration of tRT. The primary outcomes were overall survival (OS) and progression‐free survival (PFS). Cox regression analysis was utilized to identify potential independent predictors of prognosis and to compare the treatment outcomes across various patient subgroups. Treatment‐related toxicities across both cohorts were compared using the Chi‐squared test. Results: A total of 99patients were eligible for the study, out of which 55 received tRT. The medianduration of follow‐up was 39 months. Remarkably, patients who received tRTdemonstrated superior OS and PFS in comparison to those who did not (P < 0.05). Subgroup analysis further confirmed these findings. Multivariate analysisidentified treatment group and liver metastasis as independent prognosticfactors (P < 0.05). The incidence of grade 3‐4 adverse events showed nostatistically significant difference between the two cohorts. Conclusions: Thus, weconfirmed that the addition of tRT to the conventional regimen of first‐linechemotherapy and immunotherapy yields better survival outcomes without asignificant increase in toxicity. [ABSTRACT FROM AUTHOR]

Background: To evaluate the outcomes of first‐line imatinib versus nilotinib treatment for chronic myeloid leukemia in the chronic phase (CML‐CP) in real‐world clinical practice. Methods: A propensity score analysis was performed to eliminate imbalances between the treatment groups. In the analysis, 163 patients in the nilotinib group and 163 patients in the matched imatinib group were retrospectively evaluated. Results: Nilotinib‐treated patients achieved complete cytogenetic response (CCyR) and major molecular response more rapidly than imatinib‐treated patients. However, there was no significant difference in 5‐year overall survival (OS) or progression‐free survival (PFS) between the two groups (OS: 94.3% vs. 90.5%, p = 0.602; PFS: 92.9% vs. 88.0%, p = 0.614). Nilotinib‐treated patients had a higher failure‐free survival (FFS) and event‐free survival (EFS) than imatinib‐treated patients (FFS: 71.7% vs. 54.3%, p = 0.040; EFS: 71.7% vs. 53.5%, p = 0.025). Conclusions: This retrospective analysis from clinical practice did not confirm any benefit of frontline nilotinib treatment for OS and PFS; however, it did demonstrate higher FFS and EFS in the nilotinib cohort. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate whether inosine enhances the efficacy of immune‐checkpoint inhibitors in human malignant solid tumors. Methods: This single‐center, prospective, randomized, open‐label study was conducted, from January 2021 to December 2022, in Beijing Friendship Hospital, Capital Medical University, and participants were randomly assigned (1:1) to either the inosine (trial) or non‐inosine (control) group that received inosine (dosage: 0.2 g, three times/day) + PD‐1/PD‐L1 inhibitor or only PD‐1/PD‐L1 inhibitor ± targeted ± chemotherapy, respectively. Efficacy was assessed every 6 weeks (i.e., after every two–three treatment cycles). The primary endpoint was the objective response rate (ORR); the secondary endpoints were disease control rate, overall survival (OS), and progression‐free survival (PFS). The trial was registered at ClinicalTrials.gov (NCT05809336). Results: Among the 172 participants with advanced malignant solid tumors, 86 each were assigned to the inosine and non‐inosine groups, wherein the median PFS (95% CI) was 7.00 (5.31–8.69) and 4.40 (3.10–5.70) months, respectively (hazard ratio [HR] 0.63; 95% CI 0.44–0.90, p = 0.011), and the ORR was 26.7% and 15.1%, respectively (p = 0.061). In the inosine and non‐inosine groups, the median OS was not reached and was 29.67 (95% CI 17.40–41.94) months, respectively (HR 1.05 [95% CI 0.59–1.84], p = 0.874). Compared with the non‐inosine group, the median PFS and ORR of the inosine group were significantly prolonged and improved in the multiple exploratory subgroup analyses. The safety analysis showed that Grades 3 and 4 adverse reactions occurred in 25 (29%) and 31 (36%) patients in the inosine and non‐inosine groups, respectively, and tended to decrease in the inosine group compared with the non‐inosine group. Conclusion: Inosine had a tendency to enhance the efficacy of immune‐checkpoint inhibitors and reduced immunotherapy‐related adverse reactions. Compared with the control group, the median progression‐free survival was significantly prolonged and the objective response rate tended to increase in the inosine group. Inosine has a tendency to enhance the efficacy of immune‐checkpoint inhibitors and reduce immunotherapy‐related adverse reactions in clinical applications. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to analyse the outcomes of patients with large B‐cell lymphoma (LBCL) treated with chimeric antigen receptor T‐cell therapy (CAR‐Tx), with a focus on outcomes after CAR T‐cell failure, and to define the risk factors for rapid progression and further treatment. Methods: We analysed 107 patients with LBCL from the Czech Republic and Slovakia who were treated in ≥3rd‐line with tisagenlecleucel or axicabtagene ciloleucel between 2019 and 2022. Results: The overall response rate (ORR) was 60%, with a 50% complete response (CR) rate. The median progression‐free survival (PFS) and overall survival (OS) were 4.3 and 26.4 months, respectively. Sixty‐three patients (59%) were refractory or relapsed after CAR‐Tx. Of these patients, 39 received radiotherapy or systemic therapy, with an ORR of 22% (CR 8%). The median follow‐up of surviving patients in whom treatment failed was 10.6 months. Several factors predicting further treatment administration and outcomes were present even before CAR‐Tx. Risk factors for not receiving further therapy after CAR‐Tx failure were high lactate dehydrogenase (LDH) levels before apheresis, extranodal involvement (EN), high ferritin levels before lymphodepletion (LD) and ECOG PS >1 at R/P. The median OS‐2 (from R/P after CAR‐Tx) was 6.7 months (6‐month 57.9%) for treated patients and 0.4 months (6‐month 4.2%) for untreated patients (p < 0.001). The median PFS‐2 (from R/P after CAR‐Tx) was 3.2 months (6‐month 28.5%) for treated patients. The risk factors for a shorter PFS‐2 (n = 39) included: CRP > limit of the normal range (LNR) before LD, albumin < LNR and ECOG PS > 1 at R/P. All these factors, together with LDH > LNR before LD and EN involvement at R/P, predicted OS‐2 for treated patients. Conclusion: Our findings allow better stratification of CAR‐Tx candidates and stress the need for a proactive approach (earlier restaging, intervention after partial remission achievement). [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the safety, tolerability, and preliminary efficacy of multiple doses of pegylated irinotecan (JK1201I) as a second‐line monotherapy for treating small‐cell lung cancer (SCLC) patients. Methods: According to the "3 + 3" dose‐escalation principle, patients received intravenous JK1201I at 180 or 220 mg/m2 once every 3 weeks for four cycles. Progression‐free survival (PFS), overall survival (OS), median progression‐free survival (mPFS), and median overall survival (mOS) were evaluated. The Kaplan–Meier method was used to analyze PFS and overall OS. Brookmeyer and Crowley's method was used for mPFS and mOS. Results: This study included 29 patients with stage III–IV SCLC (stage IIIa, n = 1; stage IIIb, n = 1; and stage IV, n = 27). Of these, 26 patients were enrolled in the 180 mg/m2 dose group, and 3 patients were enrolled in the 220 mg/m2 dose group. No dose‐limiting toxicity (DLT) was noted during the first 28 days of treatment. Grade 3 or higher adverse events were recorded in the 180 mg/m2 group, including diarrhea (11.5%, 3/26), neutropenia (7.7%, 2/26), and leukopenia (7.7%, 2/26). In the 220 mg/m2 group, one patient (33.3%, 1/3) experienced neutropenia or leukopenia. In the 180 mg/m2 group, 38.5% (10/26) of patients achieved an objective response rate (ORR), with a disease control rate (DCR) of 73.1% (19/26). The mPFS and mOS were 3.4 and 12.1 months, respectively. In the 220 mg/m2 group, one patient had stable disease, and one had progressive disease (PD). The ORR, DCR, mPFS, and mOS were 0% (0/3) and 33.3% (1/3), 2.7 months and 2.7 months, respectively. Conclusion: JK1201I exhibits promising efficacy and relatively low toxicities as a second‐line monotherapy for SCLC, warranting further large‐scale clinical studies to evaluate its efficacy in greater detail. [ABSTRACT FROM AUTHOR]

Background: Autologous hematopoietic cell transplantation (HCT) among Multiple myeloma (MM) cases has resulted in greater response rates, higher overall survival (OS) and event-free survival (EFS) over the last two decades compared with the outcome of comparable individuals given conventional treatment. We aimed at this study to determine the prognostic value of the time interval between end of induction chemotherapy and autologous stem cell transplantation among multiple myeloma patients. Methods: This observational retrospective cohort study was held at Nasser Institute, Dar El-Salam Hospital and El-Sheikh Zayed Hospital on 211 cases with an initial diagnosis of MM during the study period (2017-2022). We evaluated the influence of the time interval between the end of induction of chemotherapy and Autologous Stem Cell Transplantation on free survival, relapse-free survival and overall survival. Results: There was a statistically significant relation between relapse-free survival and interval from last chemotherapy date to stem cell infusion among studied patients (significantly lower 26.0 ± 1.67 months in patients with interval>60 days vs. 56.32 ± 2.22 months in patients with interval≤60 days and with increasing interval quartile (with p<0.001 for each). Similarly, there was a statistically significant relation between overall survival and interval from last chemotherapy date to stem cell infusion among studied patients (significantly lower 58.28 ± 3.97 months in patients with interval>60 days vs. 67.48 ± 1.45 months in patients with interval≤60 days with P value =0.004). Conclusions: The present study demonstrated the prognostic value of the time interval between the end of induction of the chemotherapy and autologous stem cell transplantation in multiple myeloma cases, as the overall survival rate was substantially lower in patients whose intervals were greater than 60 days and with increasing interval quartiles. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer is the third most common type of cancer worldwide. Gastric cancer has a 15% to 20% 5-year overall survival rate, even if the disease just affects the stomach wall. The prognosis is favorable if tumors and their precursors are discovered early on. The current study intended to enhance the prognosis of patients suffering from early-stage stomach cancer. Methods: In this study, 24 patients with stomach cancer who attended to Zagazig University Hospitals' outpatient clinic were included. Every patient underwent a complete medical history, a general examination, and an abdominal examination that included PR and PV. Laboratory tests were performed. Along with gastroscopy and biopsies, all patients also underwent CT, ultrasonography, and CXR scans. Results: There were six women and eighteen men in the study. The distal portion of the stomach was the site of malignancy in all 100 cancer patients under study. A statistically significant correlation was not observed between the sex of the cancer cases under study and either the age distribution or the tumor site. Conclusions: Laparoscopic distal gastrectomy is a safe and effective treatment that offers advantages over open conventional gastrectomy for treating stomach cancer. These advantages include a lower risk of intraoperative blood loss and overall consequences. [ABSTRACT FROM AUTHOR]

Background: In Egypt, bladder cancer (BC) is among the most common cancers. Piwi-interacting RNA associated with bladder cancer (piRABC) expression was downregulated in bladder cancer tissue. The piRABC increase TNFSF4 levels that leads to cancer cell death. This study aimed to assess the roles of piRABC and TNFSF4 in BC detection and to evaluate their roles in cancer grading and staging. Methods: Forty BC patients and 40 controls were enrolled. A quantitative real-time PCR was used to measure the expression of piRABC. ELISA kit was used for determining serum TNFSF4. Results: Compared to controls, BC patients had significantly lower PiRABC expression l and TNFSF4 levels (p<0.0001). With an area under the ROC curve of 0.938 for PiRABC and 0.874 for the TNFSF4, they were able to detect BC. On multivariate analysis, low PiRABC and TNFSF4 levels were significant independent predictive factors of BC (AOR = 133 and 12.4, respectively). With more advanced BC stages, PiRABC expression displayed a negative trend. For BC patients' overall survival, PiRABC and TNFSF4 may be significant independent prognostic factors (p = 0.038 and 0.026, respectively). Conclusions: Decreased levels of piRABC expression and TNFSF4 appear to be independent predictors of BC. The low expression of piRABC had accepted prediction criteria for BC better than TNFSF4. The piRABC showed a decreasing trend with tumor grading and staging, while TNFSF4 exhibited a declining tendency throughout BC stages, despite having a small impact in BC grading. Greater expression of TNFSF4 and piRABC was linked to prolonged patient survival rates. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer is the most frequent type of gynecological cancer following malignancies of the cervix and uterus and has the greatest death rate among gynecological malignancies. Almost two thirds of the patients have extensive intra-abdominal illness, ascites and cachexia due to malnourishment. Furthermore, systemic inflammation is crucial for the development and advancement of cancer. Therefore, it is imperative to identify relative biomarkers to forecast treatment outcomes and prognosis. Aim: To evaluate the importance of preoperative prognostic nutritional index (PNI) in ovarian cancer. To assess retrospectively association between preoperative Prognostic Nutritional Index and prognosis in patients with ovarian cancer, and to evaluate its important on disease free survival and overall survival. Methods: This study retrospective cohort observational study was conducted at Medical Oncology Department, Faculty of Medicine, Zagazig University. The preoperative peripheral blood neutrophil count was computed as follows: 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per mm3). Using the web application "Cutoff Finder," the ideal PNI cut off value for overall survival (OS) was determined. Results: The 47.895 cutoff value discriminated patients into the high-PNI and low-PNI groups. There was significant difference between the two groups. A low preoperative PNI was associated with an advanced FIGO stage, CA125, ascites, residual of disease, body mass index and significant longer OS and progression free survival in patients with high-PNI. Conclusions: Preoperative PNI can be used as a simple and useful marker for predicting chemotherapeutic response and survival prognosis in patients with Ovarian Cancer. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is one of the most aggressive malignant tumors of the brain. We queried PubMed for articles about molecular predictor markers in GBM. This scoping review aims to analyze the most important outcome predictors in patients with GBM and to compare these factors in terms of absolute months of survival benefit and percentages. Performing a gross total resection for patients with GBM undergoing optimal chemo- and radiotherapy provides a significant benefit in overall survival compared to those patients who received a subtotal or partial resection. However, compared to IDH-Wildtype GBMs, patients with IDH-Mutant 1/2 GBMs have an increased survival. MGMT promoter methylation status is another strong outcome predictor for patients with GBM. In the reviewed literature, patients with methylated MGMT promoter lived approximately 50% to 90% longer than those with an unmethylated MGMT gene promoter. Moreover, KPS is an important predictor of survival and quality of life, demonstrating that we should refrain from aggressive surgery in important brain areas. As new therapies (such as TTFs) emerge, we are optimistic that the overall median survival will increase, even for IDH-Wildtype GBMs. In conclusion, molecular profiles are stronger outcome predictors than the extent of neurosurgical resection for GBM. [ABSTRACT FROM AUTHOR]

The early detection of tumors is one of the key factors in increasing overall survival in cancer patients. A wide range of cancers still do not have a system of early diagnosis; therefore, the development of new non-invasive tools in this line is essential. Accordingly, the objective of our work was to develop a non-invasive screening method for the early detection of various carcinomas in plasma using a panel that combines two markers using RT-qPCR. A retrospective case-control study was conducted to develop a cancer screening test based on the detection of stromal and epithelial biomarkers (COL1A2 and KRT19) in plasma. The expression of biomarkers was evaluated using multiplex quantitative PCR applied to 47 cases with non-metastatic tumors and 13 control participants. For both biomarkers, a cut-off value was stablished using Youden's J index through ROC curve analysis and areas under the curve (AUC) were calculated. The plasma mRNA expression level of both biomarkers was significantly higher in diseased versus healthy patients. Moreover, ROC curve analysis showed an AUC value of 0.897 for the combined model. This model also resulted in a cutoff value of 0.664, as well as a sensitivity of 83% and a specificity of 84.6%. These results suggest that the plasma expression levels of COL1A2 and KRT19 could a have potential role in detecting various types of cancer at the early stages. The combined analysis of both stromal and epithelial biomarkers would provide a non-invasive screening method that would allow us to differentiate patients with an active neoplastic process. [ABSTRACT FROM AUTHOR]

Immune activation status determines non-small cell lung cancer (NSCLC) prognosis, with reported positive/negative associations for T helper type 2 (TH2) responses, including allergen-specific IgE and eosinophils. Our study seeks to explore the potential impact of these comorbid immune responses on the survival rates of patients with NSCLC. Our retrospective study used data from the Data Warehouse of the German Center for Lung Research (DZL) and Lung Biobank at Thoraxklinik Heidelberg. We estimated the association of blood eosinophilia and neutrophilia on survival rates in an inflammatory cohort of 3143 patients with NSCLC. We also tested sensitization to food and inhalants and high-sensitivity C-reactive protein (hs-CRP) in a comorbidity cohort of 212 patients with NSCLC. Finally, we estimated the infiltration of immune-relevant cells including eosinophils, T-cells, and mast cells in a tissue inflammatory sub-cohort of 60 patients with NSCLC. Sensitization to at least one food or inhalant (sIgE) was higher in patients with adenocarcinoma (adeno-LC) than the non-adenocarcinoma (non-adeno-LC). Furthermore, hs-CRP was higher in non-adeno-LC compared with adeno-LC. Peripheral inflammation, particularly eosinophilia and neutrophilia, was associated with poor survival outcomes in NSCLC with a clear difference between histological subgroups. Finally, blood eosinophilia was paralleled by significant eosinophil infiltration into the peritumoral tissue in the lung. This study provides novel perspectives on the crucial role of peripheral inflammation, featuring eosinophilia and neutrophilia, with overall survival, underscoring distinctions between NSCLC subgroups (adeno-LC vs. non-adeno-LC). Peripheral eosinophilia enhances eosinophil infiltration into tumors. This sheds light on the complex interplay between inflammation, eosinophil infiltration, and NSCLC prognosis among various histological subtypes. Further studies are required to underscore the role of eosinophils in NSCLC among different histological subgroups and their role in shaping the tumor microenvironment. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR) T-cell therapies have revolutionised the field of haematological malignancies by achieving impressive remission rates in patients with highly refractory haematological malignancies, improving overall survival. To date, six commercial anti-CD19 and anti-BCMA CAR T-cell products have been approved by the Food and Drug Administration (FDA) for the treatment of relapsed/refractory B-cell haematological malignancies and multiple myeloma. The indications for CAR T-cell therapies are gradually expanding, with these therapies being investigated in a variety of diseases, including non-malignant ones. Despite the great success, there are several challenges surrounding CAR T-cell therapies, such as non-durable responses and high-grade toxicities. In addition, a new safety concern was added by the FDA on 28 November 2023 following reports of T-cell malignancies in patients previously treated with either anti-CD19 or anti-BCMA autologous CAR T-cell therapies both in clinical trials and in the real-world setting. Since then, several reports have been published presenting the incidence and analysing the risks of other secondary malignancies after CAR T-cell therapies. In this opinion article, the current landscape of secondary malignancies after CAR T-cell therapies is presented, along with a proposed strategy for future research aiming at potentially diminishing or abrogating the risk of developing secondary malignancies after CAR T-cell therapies. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with a poor prognosis and limited treatment options. This study evaluates the prognostic value of stromal markers in TNBC, focusing on the tumor–stroma ratio (TSR) and overall stroma ratio (OSR) in whole slide images (WSI), as well as the expression of type-I collagen, type-III collagen, and fibrillin-1 on tissue microarrays (TMAs), using both visual assessment and digital image analysis (DIA). A total of 101 female TNBC patients, primarily treated with surgery between 2005 and 2016, were included. We found that high visual OSR correlates with worse overall survival (OS), advanced pN categories, lower stromal tumor-infiltrating lymphocyte count (sTIL), lower mitotic index, and patient age (p < 0.05). TSR showed significant connections to the pN category and mitotic index (p < 0.01). High expression levels of type-I collagen (>45%), type-III collagen (>30%), and fibrillin-1 (>20%) were linked to significantly worse OS (p = 0.004, p = 0.013, and p = 0.005, respectively) and progression-free survival (PFS) (p = 0.028, p = 0.025, and p = 0.002, respectively), validated at the mRNA level. Our results highlight the importance of stromal characteristics in promoting tumor progression and metastasis and that targeting extracellular matrix (ECM) components may offer novel therapeutic strategies. Furthermore, DIA can be more accurate and objective in evaluating TSR, OSR, and immunodetected stromal markers than traditional visual examination. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is characterized by its poor prognosis. The current challenge remains the absence of predictive biomarkers. Cytokines are crucial factors in the pathogenesis and prognosis of PDAC. Furthermore, there is growing interest in differentiating between molecular subtypes of PDAC. The aim of our study is to evaluate the association between the analyzed cytokines and the molecular subtypes of PDAC and to determine their prognostic value. Cytokine levels were measured in 73 patients, and molecular subtypes were analyzed in 34 of these patients. Transforming Growth Factor Beta 2 (TGF-β2) levels were independently associated with the basal-like and null subtypes. In patients with locally advanced and metastatic PDAC, elevated levels of interleukin (IL)-1α, IL-1β, IL-6, IL-8, IL-9, and IL-15 were associated with a higher risk of progression during first-line treatment, and increased levels of IL-1β, IL-6, IL-8, IL-9, and IL-15 were related to increased mortality. Furthermore, a significant association was observed between higher percentiles of IL-6 and IL-8 and shorter progression-free survival (PFS) during first-line treatment, and between higher percentiles of IL-8 and shorter overall survival (OS). In the multivariate analysis, only elevated levels of IL-8 were independently associated with a higher risk of progression during first-line treatment and mortality. In conclusion, the results of our study suggest that cytokine expression varies according to the molecular subtype of PDAC and that cytokines also play a relevant role in patient prognosis. [ABSTRACT FROM AUTHOR]

Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell malignancy worldwide. Molecular classifications have tried to improve cure rates. We prospectively examined and correlated the mutational landscape with the clinical features and outcomes of 185 Mexican patients (median age 59.3 years, 50% women) with newly diagnosed DLBCL. A customized panel of 79 genes was designed, based on previous international series. Most patients had ECOG performance status (PS) < 2 (69.2%), advanced-stage disease (72.4%), germinal-center phenotype (68.1%), and double-hit lymphomas (14.1%). One hundred and ten (59.5%) patients had at least one gene with driver mutations. The most common mutated genes were as follows: TP53, EZH2, CREBBP, NOTCH1, and KMT2D. The median follow-up was 42 months, and the 5-year relapse-free survival (RFS) and overall survival (OS) rates were 70% and 72%, respectively. In the multivariate analysis, both age > 50 years and ECOG PS > 2 were significantly associated with a worse OS. Our investigation did not reveal any discernible correlation between the presence of a specific mutation and survival. In conclusion, using a customized panel, we characterized the mutational landscape of a large cohort of Mexican DLBCL patients. These results need to be confirmed in further studies. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Hepatic steatosis is highly prevalent in people living with HIV. It remains unclear whether HIV in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with greater risks of liver disease progression and cardiovascular disease (CVD). We aim to evaluate the impact of HIV infection on risks of liver and CVD outcomes among US Veterans with MASLD. METHODS: Using national Veterans Administration data from 2010 to 2022, we created a propensity score-matched cohort of MASLD patients with vs without HIV. Primary outcomes were incidence of cirrhosis and hepatocellular carcinoma (HCC) among patients with vs without HIV and patients with MASLD-HIV on antiretroviral therapy (ART) vs not on ART. Secondary outcomes included incidence of major adverse cardiovascular events and overall survival. RESULTS: The propensity-matched cohort included 920 MASLD patients with HIV and 920 MASLD patients without HIV and was similar in demographics and comorbidities. Compared with MASLD patients without HIV, incidences of cirrhosis and HCC were similar among MASLD with HIV. Compared with MASLD patients without HIV, incidence of major adverse cardiovascular event was higher among MASLD patients with HIV (5.18 vs 4.48 per 100 person-years, P = 0.03). Overall 5-year survival was significantly lower among MASLD patients with HIV and even lower among those not on ART. DISCUSSION: Among US Veterans with MASLD, concurrent HIV infection, and particularly not being on ART, is associated with greater risks of CVD and decreased overall survival. No differences in risks of cirrhosis or HCC were observed. [ABSTRACT FROM AUTHOR]

Background: A minority of patients with MSS tumors present a high tumor mutation burden (TMB) without underlying MMR defects. Methods: Publicly available genomic series were assessed for identification of patients with MSS gastric gastroesophageal junction, and esophageal adenocarcinomas and a high TMB, defined as more than 10 mutations per Mb. These were compared with MSS cancers and a low TMB for genetic alterations and for survival outcomes. Results: Patients with MSS cancers with high TMB in the MSK series were older but did not differ in other clinicopathologic parameters compared with MSS patients with low TMB. Mutations in tumor suppressors TP53 and APC and oncogenes KRAS and ERBB4 as well as amplifications of ERBB2 were more prevalent in the high TMB group of MSS cancers. Mutations in DDR associated genes, in epigenetic modifiers and in genes associated with immune response were more prevalent in the hIgh TMB group patients. However, high TMB was not associated with an improved survival in MSS gastric/gastroesophageal junction/esophageal adenocarcinomas (Log Rank p = 0.5). Conclusion: MSS Gastric/gastroesophageal junction/esophageal adenocarcinomas with TMB above 10 mutations per Mb possess a genomic landscape with increased alteration frequencies in common gastroesophageal cancer genes and pathways. [ABSTRACT FROM AUTHOR]

Background/Objectives: We evaluated the outcomes of patients undergoing en bloc total vertebrectomy at our institution within the last three decades. The aim of our study was to analyse the oncological and neurological outcomes and the changes over time. Methods: We included 22 consecutive patients treated with a total vertebrectomy at our institution between January 1990 and December 2022. The standard follow-up protocol for sarcoma patients was performed. Early complications were defined as complications within the first three months postoperatively. Local recurrence was defined as the reoccurrence of a tumour at least four months after surgery. Adequate statistical methods were applied to evaluate the survival rates and the influence of potential risk factors. A p-value of <0.05 was considered statistically significant. Results: From 1990 to 2010, five total vertebrectomies were performed each decade, whereas twelve patients underwent the procedure in the period from 2010 to 2022. The mean follow-up period was 101.25 months (±112; 2–339). The one-, five- and ten-year overall survival rates were 91% (CI = (0.79; 1.00)), 59% (CI = (0.37; 0.81)) and 51% (CI = (0.27; 0.75)), respectively. For soft tissue tumours, the average overall survival was 6.2 years, whereas, for bone sarcomas, it was 13.6 years. None of the patients with wide surgical margins developed local recurrence. Complications necessitating revision procedures occurred in 54% of all cases. Conclusions: A total vertebrectomy is a highly demanding procedure, requiring accurate patient selection, meticulous preoperative planning and a highly collaborative interdisciplinary team. Adequate surgical treatment seems to be indispensable when aiming for curative treatment. Owing to the rarity of the indications, this procedure should be restricted to large tumour centres. [ABSTRACT FROM AUTHOR]

Background: 25 to 50% of patients suffering from colorectal cancer develop liver metastases. The incidence of regional lymph node (LN) metastases within the liver is up to 14%. The need for perihilar lymph node dissection (LND) is still a controversial topic in patients with colorectal liver metastases (CRLM). This study investigates the role of perihilar LND in patients with CRLM. Methods: For this retrospective study, patients undergoing surgery for CRLM at the University Hospital Basel between May 2009 and December 2021 were included. In patients with perihilar LND, LN were stained for CK22 and examined for single tumour cells (<0.2 mm), micro- (0.2–2 mm), and macro-metastases (>2 mm). Results: 112 patients undergoing surgery for CRLM were included. 54 patients underwent LND, 58/112 underwent liver resection only (LR). 3/54 (5.6%) showed perihilar LN metastases in preoperative imaging, and in 10/54 (18.5%), micro-metastases could be proven after CK22 staining. Overall complications were similar in both groups (LND: 46, 85.2%; LR: 48, 79.3%; p = 0.800). The rate of major complications was higher in the LND group (LND: 22, 40.7%; LR: 18, 31%, p = 0.002). Median recurrence-free survival (RFS) (LND: 10 months; LR: 15 months, p = 0.076) and overall survival (OS) were similar (LND: 49 months; LR: 60 months, p = 0.959). Conclusion: Preoperative imaging is not sensitive enough to detect perihilar LN metastases. Perihilar LND enables precise tumour staging by detecting more lymph node metastases, especially through CK22 staining. However, perihilar LND does not influence oncologic outcomes in patients with CRLM. [ABSTRACT FROM AUTHOR]

The results of a prospective, multi-institutional randomized trial developed to assess the equality of sublobar resection versus standard lobectomy were first published in 1995. They concluded that, compared with lobectomy, sublobar resections did not show any significant improvement either in terms of postoperative morbidity and mortality nor in terms of late post-resectional cardiorespiratory function. Moreover, due to the higher mortality and local recurrence rate related to sublobar resection, lobectomy had to be judged as the best surgical option for patients diagnosed with peripheral early-stage non-small-cell lung cancer. Since then, lobectomy has been considered the best surgical option for fit patients suffering from early-stage non-small cell lung cancer. In 2022 and 2023, three non-inferiority randomized trials were published, comparing lobectomy with the sublobar resection in T1a N0 patients whose tumors were up to 2 cm in size. Although presenting some important differences, all three trials met their primary endpoints, disclosing the non-inferiority of sublobar resections in terms of overall and disease-free survival. This narrative review aims to compare the newly published results of these trials as well as to report results from recent non-randomized studies on this topic. [ABSTRACT FROM AUTHOR]

Background/Objectives: The prolonged time to reach investigation and management decisions in non-small cell lung cancer (NSCLC) patients can negatively impact long-term outcomes. This retrospective cohort study aims to assess the impact of a multidisciplinary team conference (MDT) on NSCLC care quality and outcomes. Methods: This retrospective study included resectable NSCLC patients who underwent pulmonary resection at Chiang Mai University Hospital, Thailand, from 1 January 2009 to 31 December 2021. Patients were divided into two groups: non-MDT and MDT groups, based on the initiation of MDT on 1 March 2018. The study compared overall survival, disease-free survival, and waiting times for investigation and surgery between the two groups. The effect of MDT on these outcomes was analyzed using multivariable analysis with inverse-probability weighting propensity scores. Results: The study included 859 patients, with 583 in the non-MDT group and 276 in the MDT group. MDT groups had a higher proportion of stage I and II NSCLC patients undergoing pulmonary resection (78.6% vs. 59.69%, p < 0.001). In multivariable analysis, patients in the MDT group had a significantly higher likelihood of longer survival compared to the non-MDT group (adjusted HR 0.23, 95% CI 0.09–0.55). Median waiting times for bronchoscopy (3 days vs. 12 days, p = 0.012), pathologic report (7 days vs. 13 days, p < 0.001), and surgery scheduling (18 days vs. 25 days, p = 0.001) were significantly shorter in the MDT group. Conclusions: An MDT has a survival benefit in NSCLC care and improves waiting times for investigation and treatment steps. Further studies are needed to validate these results. [ABSTRACT FROM AUTHOR]

Background: Advancements in managing stage III melanoma have involved the implementation of adjuvant therapies alongside a simultaneous decrease in the utilization of completion lymph node dissection (CLND) following positive sentinel node biopsy (SLNB). Methods: This retrospective study from the University of Turin's Dermatology Clinic analyzed relapse-free survival (RFS) and overall survival (OS) among stage III melanoma patients (n = 157) who underwent CLND after positive SLNB versus those who did not receive such procedure. Results: Patients without CLND had a median RFS of 49 months (95% CI 42-NA), while CLND recipients showed 51 months (95% CI 31-NA) (p = 0.139). The 48-month OS for non-CLND patients was 79.8% (95% CI 58.2–91.0) versus 79.2% (95% CI 67.5–87.0) for CLND recipients (p = 0.463). Adjusted Hazard Ratios through inverse probability treatment weighting revealed the impact of CLND to be insignificant on RFS (aHR 0.90, 95% CI 0.37–2.22) and marginal on OS (aHR 0.41, 95% CI 0.13–1.21). Conversely, adjuvant therapy significantly reduced the risk of relapse (aHR 0.46, 95% CI 0.25–0.84), irrespective of CLND. Conclusions: This study corroborates the growing evidence that CLND after positive SLNB does not enhance RFS or OS, while emphasizing the crucial role of adjuvant therapy, be it immunotherapy or targeted therapy, in reducing the risk of relapse in melanoma patients with positive SLNB. [ABSTRACT FROM AUTHOR]

Background: The National Comprehensive Cancer Network (NCCN)-recommended treatment for patients with borderline-resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC) involves a combination of neoadjuvant FOLFIRINOX chemotherapy and the curative surgical resection of the tumor. This study seeks to identify the clinical, radiological, laboratory, and pathologic predictors that can anticipate the oncological outcomes of patients. Methods: In this study, we conducted a retrospective analysis of patients who had undergone curative surgical resection for BRPC, LAPC, or resectable disease with high-risk features after receiving neoadjuvant FOLFIRINOX at two institutions. We evaluated by means of multivariate analysis whether clinical and laboratory response, tumor markers, radiological response, and pathologic tumor response grade correlated with overall survival (OS) and disease-free survival (DFS). Results: The study enrolled a total of 70 patients with BRPC, LAPC, and resectable disease with high-risk features who underwent resection after neoadjuvant FOLFIRINOX. Age above 65 years and fewer than nine cycles of chemotherapy (OR 4.2; 95% CI 1.4–12.0; p-value 0.007); locally advanced tumors after neoadjuvant treatment (NAT) (OR 7.0; 95% CI 1.9–25.7; p-value 0.003); and lymph node disease and histological tumor regression grade 2 and 3 (OR 4.3; 95% CI 0.9–19.2; p-value 0.05) were risk factors linked to adverse OS and DFS. The median OS and DFS were 33 (22–43.9) months and 16.5 (11.3–21.6) months, respectively. Conclusions: Classification as a LA tumor after NAT was the only preoperative radiological factor that predicted adverse survival in patients undergoing curative surgery after NAT. Other clinical, biochemical, and radiological measures of response were not found to predict OS. Patient age, the cumulative administration of more than eight cycles of chemotherapy, and a significant pathological response were associated with better OS. The results of this study are important for treatment decision-making and prognostication in patients with BRPC and LAPC. [ABSTRACT FROM AUTHOR]

Rectal cancer shows specific characteristics in terms of pattern of recurrence, which occurs commonly at both local and distant sites. The standard of care for locally advanced rectal cancer (LARC) including neoadjuvant chemoradiotherapy, followed by surgery based on the total mesorectal excision principles leads to a reduction in the rates of local recurrences to 6–7% at 5 years. However, the outcomes among those with high-risk lesions remain unsatisfactory. On the contrary, neoadjuvant chemoradiotherapy results in long-term morbidities among those with low-risk lesions. Furthermore, the overall survival benefit of neoadjuvant therapy is still a subject to be debated, except for patients with complete or near-complete response to neoadjuvant therapy. Total neoadjuvant therapy (TNT) is a new paradigm of management of high-risk rectal cancer that includes early administration of the most effective systemic therapy either before or after neoadjuvant radiotherapy with or without chemotherapy prior to surgery with or without adjuvant chemotherapy. TNT potentially improves disease-free survival, even though whether it can prolong survival has been debatable. Recently, neoadjuvant chemotherapy only has been proved to be non-inferior to neoadjuvant chemoradiotherapy in patients with low-risk lesions. This review intends to review the current evidences of neoadjuvant therapy and propose a more customized paradigm of management of LARC. [ABSTRACT FROM AUTHOR]

Background: Although survival outcomes for neuroendocrine liver metastases (NETLM) are improved with liver-direct therapies (LDT), including hepatic debulking and nonsurgical trans-arterial embolization, the benefit is less established in the setting of concurrent extrahepatic disease (EHD). We performed a population-based study to characterize the rates of LDT being performed for NETLM with EHD patients and whether LDT is associated with survival outcomes. Methods: Patients with NETLM and EHD were identified using the California Cancer Registry database merged with data from the California Office of Statewide Health Planning and Development between 2000 and 2012. Demographics, clinical characteristics, and survival outcomes were analyzed for these patients with and without LDT. Results: 327 NETLM patients with EHD were identified. EHD sites included lung, peritoneum, bone, and brain. A total of 71 (22%) of these patients underwent LDT. Compared to NETLM with EHD patients who did not undergo LDT, patients who received LDT had longer median overall survival (27 vs. 16 months, p = 0.006). Within the LDT group, 23 patients underwent liver resection. Liver resection was associated with longer median overall survival compared to nonsurgical LDT (138 vs. 13 months, p < 0.001). Conclusions: LDT candidacy should be determined for patients on a case-by-case basis, but the presence of EHD should not preclude LDT with appropriate patient selection. [ABSTRACT FROM AUTHOR]

Cervical malignancy (CC) is the 2nd most prevalent malignancy among females, leading to cancer mortality. Primary detection of CC tumors results in an improved prognosis. CC is a malignant gynecological tumor, with few treatment options. New diagnostic and therapeutic agents are required to expand patient survival and quality of life. If CC tumors can be found at an early stage, the prognosis is much brighter. New diagnostic and therapeutic agents are needed to increase patient survival and quality of life. In this work, we performed whole-exome sequencing utilizing V5 (Illumina platform) 10 samples, 5 control and 5 CC tumour tissue, and we compared the results with transcriptome studies. KMT2C variations were shown to be among the most vicious in this analysis. From an Indian viewpoint, we found a plethora of SNVs and mutations, including those with known, unknown, and possible effects on health. Based on our findings, we know that the KMT2C gene is on chr. Seven and in exon 8, all three recognized variants are missense, synonymous, coding synonymous, non-coding variants, and GnomAD MAF (− 0.05). The variation at position (7:152265091, T > A, SNV 62478356) in KMT2C is unique, potent, and pathogenic. The missense coding transcript CIQTNF maps to chromosome 7 and displays T > C SNV. In addition, we performed single strand conformational polymorphism analysis on 64 samples and further confirmed them using Sanger sequencing to understand and verify the mutations. KMT2C shows a log FC value of − 1.16. Understanding emerging harmful mutations from an Indian viewpoint is facilitated by our bioinformatics-based, extensive correlation studies of WES analysis. Potentially harmful and new mutations were found in our preliminary analysis; among these ten top mutated genes, KMT2C and CIQTNF were altered in ten cases of CC with an Indian phenotype. [ABSTRACT FROM AUTHOR]

Simple Summary: This study focuses on Stage IIIA-N2 non-small cell lung cancer (NSCLC), which occurs when lung cancer has spread to lymph nodes in the centre of the chest but not to distant parts of the body. This type of cancer is difficult to treat, and survival rates remain low despite advances in therapy. The research is based on real-world data from Guy's Thoracic Cancer Database and aims to enhance our understanding of patient outcomes and identify important factors that impact survival and disease progression. By examining various treatment strategies, the study aims to offer insights that could help tailor treatment approaches to individual patients. The findings underscore the need for personalised care and the potential benefits of incorporating newer therapeutic options, ultimately leading to better survival outcomes for patients with this challenging form of lung cancer. Background: Stage IIIA-N2 non-small cell lung cancer (NSCLC) poses a significant clinical challenge, with low survival rates despite advances in therapy. The lack of a standardised treatment approach complicates patient management. This study utilises real-world data from Guy's Thoracic Cancer Database to analyse patient outcomes, identify key predictors of overall survival (OS) and disease-free survival (DFS), and address the limitations of randomised controlled trials. Methods: This observational, single-centre, non-randomised study analysed 142 patients diagnosed with clinical and pathological T1/2 N2 NSCLC who received curative treatment from 2015 to 2021. Patients were categorised into three groups: Group A (30 patients) underwent surgery for clinical N2 disease, Group B (54 patients) had unsuspected N2 disease discovered during surgery, and Group C (58 patients) received radical chemoradiation or radiotherapy alone (CRT/RT) for clinical N2 disease. Data on demographics, treatment types, recurrence, and survival rates were analysed. Results: The median OS for the cohort was 31 months, with 2-year and 5-year OS rates of 60% and 30%, respectively. Group A had a median OS of 32 months, Group B 36 months, and Group C 25 months. The median DFS was 18 months overall, with Group A at 16 months, Group B at 22 months, and Group C at 17 months. Significant predictors of OS included ECOG performance status, lymphovascular invasion, and histology. No significant differences in OS were found between treatment groups (p = 0.99). Conclusions: This study highlights the complexity and diversity of Stage IIIA-N2 NSCLC, with no single superior treatment strategy identified. The findings underscore the necessity for personalised treatment approaches and multidisciplinary decision-making. Future research should focus on integrating newer therapeutic modalities and conducting multi-centre trials to refine treatment strategies. Collaboration and ongoing data collection are crucial for improving personalised treatment plans and survival outcomes for Stage IIIA-N2 NSCLC patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Plasmacytoid urothelial carcinoma (PUC) is a rare and aggressive histologic subtype of urothelial carcinoma of the bladder (BC) with high rates of upstaging and metastases. The aim of our study was to characterize treatment patterns and outcomes using a large national database and our institutional experiences, combating the challenge posed by the rarity of this variant. We demonstrated that, despite an improved pT0 rate associated with NAC, there remains an inconclusive overall survival increase. Additionally, PUC demonstrated a high predilection for peritoneal metastasis, further highlighting the need for investigation into more effective and subtype-tailored treatment options. Background: Plasmacytoid urothelial carcinoma (PUC) is a rare histologic subtype of urothelial carcinoma of the bladder (BC). Our objective was to characterize treatment patterns and outcomes of PUC in the NCDB and our recent institutional experience. Methods: The NCDB was queried for localized PUC cases between 2004 and 2020. Patients with PUC from a single institution (Yale School of Medicine) were also incorporated from 2021 onwards to not double-count patients. The primary outcomes were overall survival and treatment trends. Results: A total of 146 patients were included, 123 from NCDB and 23 from Yale. The median overall survival (mOS) was 28 [IQR 7.5, 50.3] months, 23 [IQR 8.4, 46.3] months for the NCDB patients, and 36 [IQR 4.3, 68.1] for the Yale patients. The mOS for patients receiving neoadjuvant chemotherapy (NAC) was 60.0 [28.0, 91.9] vs. 14.8 months [0, 34.3] for patients without NAC, p = 0.038, though the benefit was not preserved in a Cox proportional hazard analysis incorporating the clinical stage, receipt of NAC, and age. The peritoneum was the most common site of metastasis (78.3%), followed by the liver and bones. Conclusion: Our findings underscore the formidable challenge posed by PUC, emphasizing its limited response to current therapies. Despite higher pT0 rates with NAC, the OS benefit remains inconclusive, highlighting the need for more effective treatments. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer is the most common cancer and the leading cause of cancer-related deaths among women globally, with over 2.26 million new cases in women in 2020. Male breast cancer, while rare (less than 1% of cases), is treated similarly to female breast cancer despite some clinical differences. Advances in treatment, such as using genomic and immunohistochemical markers, have significantly improved survival rates for women. Men with breast cancer are often older at diagnosis, and their prognosis may differ due to age and other factors. The survival analysis conducted on 2162 patients (19 males and 2143 females) suggests that male breast cancer may have a poorer prognosis compared to female breast cancer. Breast cancer is one of the most common cancers and the leading cause of cancer death in women. Less than 1% of breast cancer cases are male breast cancers. Although there has been significant progress made in the management of breast cancer, due to its rarity among men, the question of whether men and women with breast cancer have the same treatment response and survival rate still needs to be answered. The primary goal of this study is to compare survival outcomes between male and female breast cancer patients. Material and Method: This cohort study represents a retrospective and anonymized data analysis of 2162 breast cancer cases (19 males and 2143 females), registered over a period of 12 years, from 1 January 2010 to 31 December 2021, in the Clinic of Obstetrics and Gynecology, Diakoneo Diak Klinikum Schwäbisch Hall, Germany. Results: According to the Kaplan–Meier survival analysis, the estimated overall 3-year survival rate was 91.1% for women and 88.9% for men. The log-rank test of equality of survival distributions indicated a statistically significant difference in survival times between the two groups (p = 0.009). In the subsequent age-matched Kaplan–Meier analysis, the p-value was below the significance threshold (p = 0.068). Conclusions: Male breast cancer is a rare disease that may show some particularities in terms of survival compared to female breast cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: We aimed to evaluate the role of adjuvant chemotherapy in patients who undergo pneumonectomy for pN1 NSCLC. We found no significant differences after 5 years between two cohorts (adjuvant CT and no adjuvant CT) in terms of the overall survival (p: 0.31), cancer-specific survival (p: 0.59), disease-free survival (p: 0.94), and relapse rate (p: 0.76). Patients with pN1 NSCLC that was completely resected through pneumonectomy and radical lymphadenectomy may represent a particular cohort, which could be strictly followed up without adjuvant chemotherapy. Introduction: We aimed to assess our 25-year experience in order to evaluate the role of adjuvant chemotherapy in patients who undergo pneumonectomy for pN1 NSCLC. Materials and Methods: We retrospectively reviewed the outcomes and medical records of patients undergoing pneumonectomy for NSCLC with pathological diagnosis of pN1, excluding all patients who underwent neoadjuvant treatment. We compared patients treated with adjuvant chemotherapy with patients who did not undergo neoadjuvant treatment during a follow-up soon after surgery. Gray's test was used to assess differences in the cumulative incidence of relapse or CSS between the different groups. Kaplan–Meier methods were used for drawing overall survival (OS) plots. In order to assess differences in survival between the groups, the log-rank test was used. The cumulative incidence of relapse, CSS, and OS were calculated at 1, 2, 3, 4, and 5 years of follow-up. Results: The 30-day and 90-day mortality rates of our cohort were 6% and 11,6%. Excluding the first three months after surgery (deaths linked to postoperative comorbidity), after 5 years we found no significant differences between the two cohorts (adjuvant CT and no adjuvant CT) in terms of the overall survival (OS) (p: 0.31), cancer-specific survival (CSS) (p: 0.59), disease-free survival (DFS) (p: 0.94), and relapse rate (p: 0.76). Conclusions: Patients with pN1 NSCLC that was completely resected through pneumonectomy and radical lymphadenectomy may represent a particular cohort, which could be strictly followed up without adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Sarcopenia refers to a progressive and systemic reduction in skeletal muscle mass and strength and is a primary component of cancer cachexia. This retrospective study examined the impact of the rate of muscle loss between two time points during the pretreatment period with concurrent chemoradiotherapy on the clinical outcomes during subsequent durvalumab maintenance treatment. As the results showed, patients who experienced psoas muscle loss during chemoradiotherapy had a shorter progression-free survival and experienced reduced effectiveness of durvalumab treatment. This study highlights the importance of monitoring psoas muscle changes during chemoradiotherapy to predict the success of subsequent durvalumab therapy better in non-small cell lung cancer patients. Sarcopenia assessed at a single time point is associated with the efficacy of immunotherapy, and we hypothesized that longitudinal changes in muscle mass may also be important. This retrospective study included patients with non-small cell lung cancer (NSCLC) who received durvalumab treatment after concurrent chemoradiotherapy (CCRT) between January 2017 and April 2023. Muscle loss and sarcopenia were assessed based on the lumbar skeletal muscle area. Patients with a decrease in muscle area of 10% or more during CCRT were categorized into the muscle loss group, while those with a decrease of less than 10% were categorized into the muscle maintenance group. We evaluated the relationship between muscle changes during CCRT and the efficacy of durvalumab treatment. Among the 98 patients, the muscle maintenance group had a significantly longer PFS of durvalumab treatment compared to the muscle loss group (29.2 months [95% confidence interval (CI): 17.2—not reached] versus 11.3 months [95% CI: 7.6–22.3]; p = 0.008). The multivariable analysis confirmed that muscle change was a significant predictor of a superior PFS (HR: 0.47 [95% CI: 0.25–0.90]; the p-value was less than 0.05). In contrast, the OS between the groups did not differ significantly (not reached [95% CI: 21.8 months—not reached] and 36.6 months [95% CI: 26.9—not reached]; p = 0.49). Longitudinal muscle changes during CCRT are a predictor of durvalumab's efficacy in patients with NSCLC after CCRT. [ABSTRACT FROM AUTHOR]

Simple Summary: Brain metastases from systemic cancer are the most common tumors of the central nervous system. For prostate metastases to the brain, the clinical progression is poorly understood. This retrospective study aims to elucidate clinical risk factors associated with overall survival (OS; months post-diagnosis) in prostate metastases to the brain, and then develop a nomogram to aid in clinical decision making for this vulnerable population. We identified several factors associated with survival, including race, tumor size, and the presence of additional metastases. This study should serve as a clinical framework for prognostication in metastatic prostate cancer to the brain. Brain metastases are an uncommon yet life-limiting manifestation of prostate cancer. However, there is limited insight into the natural progression, therapeutics, and patient outcomes for prostate cancer once metastasized to the brain. This is a retrospective study of 461 patients with metastatic prostate cancer to the brain with a primary outcome of median overall survival (OS). The Surveillance, Epidemiology, and End Results (SEER) database was examined using Cox regression univariate and multivariable analyses, and a corresponding nomogram was developed. The median overall survival was 15 months. In the multivariable analysis, Hispanic patients had significantly increased OS (median OS 17 months, p = 0.005). Patients with tumor sizes greater than three centimeters exhibited significantly reduced OS (median OS 19 months, p = 0.014). Patients with additional metastases to the liver exhibited significantly reduced OS (median OS 3.5 months, p < 0.001). Increased survival was demonstrated in patients treated with chemotherapy or systemic treatment (median OS 19 months, p = 0.039), in addition to radiation and chemotherapy (median OS 25 months, p = 0.002). The nomogram had a C-index of 0.641. For patients with prostate metastases to the brain, median OS is influenced by race, tumor size, presence of additional metastases, and treatment. The lack of an association between traditional prostate cancer prognosis metrics, including Gleason and ISUP grading, and mortality highlights the need for individualized, metastasis-specific prognosis metrics. This prognostic nomogram for prostate metastases to the brain can be used to guide the management of affected patients. [ABSTRACT FROM AUTHOR]

Simple Summary: In this retrospective study of 61 patients with diffuse gliomas, APT-weighted imaging in the solid tumor component provided quantitative metrics associated with WHO grade and survival. Mean APT values of the necrotic component showed high variability between subjects, warranting further investigation. These results highlight the importance of assessing the different tumor components with APT-weighted imaging, to provide useful diagnostic and prognostic information for the management of patients with gliomas. Amide Proton Transfer-weighted (APTw) imaging is a molecular MRI technique used to quantify protein concentrations in gliomas, which have heterogeneous components with varying cellularity and metabolic activity. This study aimed to assess the correlation between the component-specific APT signal of the neoplasm and WHO grade, molecular profile and survival status. Sixty-one patients with adult-type diffuse gliomas were retrospectively analyzed. APT values were semi-automatically extracted from tumor solid and, whenever present, necrotic components. APT values were compared between groups stratified by WHO grade, IDH-mutation, MGMT promoter methylation and 1- and 2-year survival status using Wilcoxon rank-sum test, adjusting for multiple comparisons. Overall survival (OS) was analyzed in the subgroup of 48 patients with grade 4 tumors using Cox proportional-hazards models. Random-effects models were used to assess inter-subject heterogeneity of the mean APT values in each tumor component. APT values of the solid component significantly differed between patients with grades 2–3 and 4 tumors (mean 1.58 ± 0.50 vs. 2.04 ± 0.56, p = 0.028) and correlated with OS after 1 year (1.81 ± 0.58 in survivors vs. 2.17 ± 0.51 in deceased patients, p = 0.030). APT values did not differ by IDH-mutation, MGMT methylation, and 2-year survival status. Within grade 4 glioma patients, higher APT kurtosis of the solid component was a negative prognostic factor (hazard ratio = 1.60, p = 0.040). Mean APT values of the necrosis showed high inter-subject variability, although most necrotic tumors were grade 4 and IDH wildtype. In conclusion, APTw imaging in the solid component provided metrics associated with glioma grade and survival status but showed weak correlation with IDH-mutation and MGMT promoter methylation status, in contrast to previous works. Further research is needed to understand APT signal variability within the necrotic component of high-grade gliomas. [ABSTRACT FROM AUTHOR]

Simple Summary: Single small primary liver cancers are curable with treatments such as surgical resection, ablation, and liver transplant; however, many patients initially receive trans-arterial chemo-embolisation (TACE), which is generally not considered a curative treatment in itself, and often go on to receive further follow-up treatments. Little is known regarding the outcomes of such patients compared to those who receive upfront ablation. Our real-world multi-centre study demonstrates that key survival outcomes are similar between those initially undergoing TACE and those receiving ablation after controlling for other key clinical variables and allowing for subsequent individualised treatment selection. Percutaneous ablation is recommended in Barcelona Clinic Liver Cancer (BCLC) stage 0/A patients with HCC ≤3 cm as a curative treatment modality alongside surgical resection and liver transplantation. However, trans-arterial chemo-embolisation (TACE) is commonly used in the real-world as an initial treatment in patients with single small HCC in contrast to widely accepted clinical practice guidelines which typically describe TACE as a treatment for intermediate-stage HCC. We performed this real-world propensity-matched multi-centre cohort study in patients with single HCC ≤ 3 cm to assess for differences in survival outcomes between those undergoing initial TACE and those receiving upfront ablation. Patients with a new diagnosis of BCLC 0/A HCC with a single tumour ≤3 cm first diagnosed between 1 January 2016 and 31 December 2020 who received initial TACE or ablation were included in the study. A total of 348 patients were included in the study, with 147 patients receiving initial TACE and 201 patients undergoing upfront ablation. After propensity score matching using key covariates, 230 patients were available for analysis with 115 in each group. There were no significant differences in overall survival (log-rank test p = 0.652) or liver-related survival (log-rank test p = 0.495) over a median follow-up of 43 months. While rates of CR were superior after ablation compared to TACE as a first treatment (74% vs. 56%, p < 0.004), there was no significant difference in CR rates when allowing for further subsequent treatments (86% vs. 80% p = 0.219). In those who achieved CR, recurrence-free survival and local recurrence-free survival were similar (log rank test p = 0.355 and p = 0.390, respectively). Our study provides valuable real-world evidence that TACE when offered with appropriate follow-up treatment is a reasonable initial management strategy in very early/early-stage HCC, with similar survival outcomes as compared to those managed with upfront ablation. Further work is needed to better define the role for TACE in BCLC 0/A HCC. [ABSTRACT FROM AUTHOR]

Simple Summary: The survival of glioblastoma (GBM) patients remains at just 12–15 months with a 5% 5 year survival despite them undergoing a harsh and brutal treatment regimen involving surgery, radiation and chemotherapy. This is because GBMs are impossible to completely resect and almost always recur at the borders of the resection margin, while the presence of the blood–brain barrier limits the amount of chemotherapy that can access the brain, requiring the patient to receive high and extremely toxic doses of chemotherapy. In this study, we demonstrate that local delivery of the chemotherapeutic drug irinotecan directly into the border of the resection margin offers a safe route of administration with none of the normal side effects associated with traditional chemotherapy. Glioblastomas are impossible to completely resect and almost always recur at the borders of the resection margin. There is no established chemotherapy regimen available to patients who recur, while systemic treatment is hampered by the blood–brain barrier. Here, we report on the first evaluation in humans of the intraparenchymal injection of irinotecan into the resection cavity after surgical resection of recurrent glioblastoma patients. The cytotoxicity of irinotecan was compared to SN-38 in primary cells from recurrent glioblastoma patients. Irinotecan was injected at multiple (~30) sites of the resection cavity wall at a depth of 3 to 5 mm. SN-38 was more cytotoxic than irinotecan at concentrations below 1 µM due to enzyme kinetics. The intraparenchymal administration of irinotecan was safe, with good wound healing and an absence of swelling, inflammation, or pseudo-abscess formation. The median survival post irinotecan administration was 32.6 weeks. The median overall survival was 30.5 months, with a two-year survival rate of 56%. This study demonstrates that local delivery of irinotecan into the brain parenchyma offers a safe route of administration over systemic delivery in the treatment of recurrent glioblastoma. [ABSTRACT FROM AUTHOR]

Simple Summary: We retrospectively evaluated the clinical outcomes of lung metastasectomy in 147 patients with pulmonary metastases from primary liver tumors at three medical centers. Multivariate analysis demonstrated that surgical resection as the initial primary liver tumor treatment and lower MELD-Na scores significantly correlated with better OS. These findings can guide thoracic surgeons in patient selection and predicting surgical outcomes. Oligopulmonary metastases from primary liver tumors are typically treated surgically. We evaluated the clinical outcomes after lung metastasectomy in patients with pulmonary metastases from primary liver tumors. We retrospectively enrolled 147 consecutive patients with lung metastases from liver cancer who had undergone pulmonary metastasectomies at three medical centers between February 2007 and December 2020. All patients were pathologically confirmed to have lung metastases from liver cancer. Among the 147 patients, 110, 17, and 20 initially underwent surgical resection, radiofrequency ablation, and transcatheter arterial embolization, respectively. The 5-year overall survival (OS) in the study cohort was 22%. Univariate analysis revealed four factors associated with better OS: surgical resection as the initial primary liver tumor treatment (p = 0.004), a disease-free interval exceeding 12 months after the initial liver surgery (p = 0.036), a lower Model for End-Stage Liver Disease (MELD)-Na score (≤20) for liver cirrhosis (p = 0.044), and the absence of local liver tumor recurrence at the time of pulmonary metastasectomy (p = 0.004). Multivariate analysis demonstrated that surgical resection as the initial primary liver tumor treatment and lower MELD-Na scores significantly correlated with better OS. Our findings can assist thoracic surgeons in selecting suitable patients for surgery and predicting surgical outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Peptide Receptor Radionuclide Therapy (PRRT) and Capecitabine/Temozolomide (CAPTEM) are cornerstones of systemic therapy for metastatic pancreatic neuroendocrine tumors (PNETs). In clinical practice, most patients receive more than one regimen, and the optimal sequence of treatments for these patients remains poorly understood. We present a real-world comparison of progression-free survival (PFS) between PRRT and CAPTEM in PNETs. Our analysis found that clinical outcomes were comparable to previously reported data in the real-world setting and were similar for both regimens. PFS for patients without extrahepatic metastases and those with MEN1, DAXX, and/or ATRX mutations might be prolonged with PRRT. Patients with grade 3 disease might fare better with CAPTEM initially. Candidates for surgical debulking or those with tumor-induced symptoms may benefit from initial treatment with CAPTEM due to the shorter time to response. Background: Peptide Receptor Radionuclide Therapy (PRRT), a form of Radioligand Therapy (RLT), and Capecitabine/Temozolomide (CAPTEM) are cornerstones of systemic therapy for metastatic pancreatic neuroendocrine tumors (PNETs). Data regarding comparative efficacy are lacking. Herein, we compare the efficacy of PRRT vs. CAPTEM as second-line/beyond regimens and treatment sequencing. Methods: Clinicopathologic, radiographic, and genomic data were captured for metastatic PNETs seen in our multi-disciplinary NET clinic between 2013 and 2023. The primary outcome was progression-free survival (PFS) after progression on a previous line of systemic therapy. The secondary outcomes were objective response rate (ORR), time to response (TTR), and overall survival (OS). Results: Fifty-nine cases were included. PFS was similar in the PRRT (n = 29) and CAPTEM (n = 30) groups (PRRT = 21.90 months vs. CAPTEM = 20.03 months; HR 0.99; p = 0.97). On subgroup analysis, PRRT had longer PFS in cases without extrahepatic metastases (26.47 months vs. 17.67 months; p = 0.03) and cases with a mutation in the MEN1, DAXX, and/or ATRX genes (28.43 months vs. 18.67 months; p = 0.03). PRRT had reduced PFS in patients with grade 3 disease (7.83 months vs. 16.33 months; p = 0.02). ORR did not vary significantly (34.78% vs. 40.91%; p = 0.67). CAPTEM responders showed shorter TTR (6.03 months vs. 11.15 months; p = 0.03). In patients who received both, OS did not vary based on the sequence (HR 1.20; p = 0.75). Conclusions: PFS, ORR, and OS are similar when using PRRT vs. CAPTEM as second-line-and-beyond therapy for patients with metastatic PNETs. However, patients with MEN1, DAXX, and/or ATRX mutations or without extrahepatic metastases might better benefit from PRRT and patients with grade 3 disease from CAPTEM. Candidates for surgical debulking or with tumor-induced symptoms may benefit from initial treatment with CAPTEM due to shorter TTR. [ABSTRACT FROM AUTHOR]

Simple Summary: Peritoneal metastases from gastric cancer are linked to a poor prognosis, with median survival ranging from 2 to 9 months. Standard treatments, including systemic chemotherapy and targeted therapies, have demonstrated only limited effectiveness. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is an experimental approach under investigation for treating these metastases, but its widespread clinical use is hindered by insufficient evidence regarding its safety and efficacy. This retrospective study presents outcomes from the first PIPAC program in Lithuania, where 32 patients underwent 71 PIPAC procedures between 2015 and 2022. Intraoperative and postoperative complications occurred in 4.2% of cases. Although reductions in peritoneal carcinomatosis index (PCI) and ascites volume were noted, they were not statistically significant. The median overall survival after PM diagnosis was 12.5 months. These findings suggest that PIPAC is a safe and feasible treatment, but further research is needed to establish its efficacy. Background: Peritoneal metastases (PM) of gastric cancer (GC) are considered a terminal condition, with reported median survival ranging from 2 to 9 months. Standard treatment typically involves systemic chemotherapy alone or combined with targeted therapy or immunotherapy, though efficacy is limited. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has emerged as a novel technique for treating GC PM, although it remains an experimental treatment under investigation. This study aimed to summarize the outcomes of GC PM treatment with PIPAC from the Lithuanian PIPAC program. Methods: All patients who underwent PIPAC for GC PM at Vilnius University Hospital Santaros Klinikos between 2015 and 2022 were included in this retrospective study. The safety of PIPAC was assessed by postoperative complications according to the Clavien–Dindo classification. Efficacy was evaluated based on the peritoneal carcinomatosis index (PCI), ascites dynamics throughout the treatment, and long-term outcomes. Results: In total, 32 patients underwent 71 PIPAC procedures. Intraoperative and postoperative morbidity related to PIPAC occurred after three (4.2%) procedures. Following PIPAC, there was a tendency towards a decrease in median PCI from 10 (Q1 3; Q3 13) to 7 (Q1 2; Q3 12), p = 0.75, and a decrease in median ascites volume from 1300 mL (Q1 500; Q3 3600) at the first PIPAC to 700 mL (Q1 250; Q3 4750) at the last PIPAC, p = 0.56; however, these differences were not statistically significant. The median overall survival after PM diagnosis was 12.5 months (95% CI 10–17), and the median survival after the first PIPAC procedure was 5 months (95% CI 4–10). Conclusions: PIPAC is a safe and feasible treatment option for GC PM; however, well-designed prospective studies are needed to fully assess its efficacy. [ABSTRACT FROM AUTHOR]

Simple Summary: Vulvar cancer is a rare cancer but has a high cure rate if diagnosed early and treated appropriately. In the early 20th century, 5-year survival rates were only 15–20% because of inadequate treatment of both the primary cancer and the groin lymph nodes. By the mid-20th century, 5-year survival rates rose to 60–70% with the introduction of the radical resection of the vulva, together with the radical resection of the groin and usually pelvic lymph nodes. Although cure rates were good, physical and psychological morbidity were high with this extensive surgery. Hence, various modifications have been proposed over the past 50 years to decrease this morbidity without compromising survival, including modifications to the extent of both the vulvectomy and lymph node dissection. This paper looks at the results these modifications have on both survival and morbidity. Vulvar cancer is a rare disease, and cure rates were low until the mid-20th century. The introduction of an en bloc radical vulvectomy and bilateral groin and pelvic lymph node dissection saw them rise from 15–20% to 60–70%. However, this very radical surgery was associated with high physical and psychological morbidity. Wounds were usually left open to granulate, and the average post-operative hospital stay was about 90 days. Many attempts have been made to decrease morbidity without compromising survival. Modifications that have proven to be successful are as follows: (i) the elimination of routine pelvic node dissection, (ii) the use of separate incisions for groin dissection, (iii) the use of unilateral groin dissection for lateral, unifocal lesions, (iv) and radical local excision with 1 cm surgical margins for unifocal lesions. Sentinel node biopsy with ultrasonic groin surveillance for patients with node-negative disease has been the most recent modification and is advocated for patients whose primary cancer is <4 cm in diameter. Controversy currently exists around the need for 1 cm surgical margins around all primary lesions and on the appropriate ultrasonic surveillance for patients with negative sentinel nodes. [ABSTRACT FROM AUTHOR]

Simple Summary: Studies analyzing specific treatment-related prognostic factors can provide important information about disease biology and improve the use of biomarkers to optimize treatment decisions. The aim of our retrospective study was to determine the prognostic performance of clinicopathological factors and blood biomarkers in patients with unresectable metastatic melanoma treated with BRAF and MEK inhibitors. A total of 199 patients were included in the multivariate analysis of the risk of progression and death. We found that primary tumor localization on the limbs, Clark invasion level V, M1c stage or M1d stage at the start of therapy, and elevated baseline serum S100B level were independently and significantly associated with poor outcomes. The present study suggests that clinicopathological factors, including primary tumor characteristics and stage of metastatic disease, as well as serum markers may provide information on the probability of survival in patients with advanced melanoma treated with BRAF and MEK inhibitors. Prognostic studies can provide important information about disease biology and improve the use of biomarkers to optimize treatment decisions. Methods: A total of 199 patients with advanced melanoma treated with BRAF + MEK inhibitors were included in our single-center retrospective study. We analyzed the risk of progression and death using multivariate Cox proportional hazard models. The predictive effect of prognostic factors on progression-free survival (PFS) was evaluated in ROC analysis. Results: We found that primary tumor localization, Clark level, pT category, baseline M stage and baseline serum S100B are independent and significant prognostic factors for PFS. The discriminative power of the combination of these factors was excellent for predicting 18 month PFS (AUC 0.822 [95% CI 0.727; 0.916], p < 0.001). Primary tumor localization on the extremities, Clark level V, baseline M1c stage or M1d stage, and elevated baseline serum S100B and LDH levels were independently and significantly associated with unfavorable overall survival (OS). Conclusion: Baseline M stage and serum S100B appear to be independent prognostic factors for both PFS and OS in melanoma patients treated with BRAF + MEK inhibitors. We newly identified significant and independent prognostic effects of primary tumor localization and Clark level on survival that warrant further investigation. [ABSTRACT FROM AUTHOR]

Simple Summary: Oropharyngeal Squamous Cell Carcinoma (OPSCC) represents a significant fraction of head and neck cancers, with a challenging five-year survival rate of only 50%. Key risk factors include tobacco and alcohol consumption and infection with human papillomavirus (HPV), particularly HPV16. Distinct biological differences exist between HPV-positive and HPV-negative OPSCC, including differences in mutation patterns and gene expression profiles. This study focuses on aldo-keto reductases (AKRs), specifically AKR1C2, which are involved in cellular stress management and detoxification processes, particularly in cisplatin-resistant tumors. This study investigates the role of AKR1C2 in HPV-positive OPSCC and its effect on patient outcomes. The findings indicate that increased levels of AKR1C2 are linked to unfavorable prognosis, particularly in male patients, while higher levels in female patients indicate a favorable prognosis. Head and Neck Squamous Cell Carcinoma (HNSCC), particularly Oropharyngeal Squamous Cell Carcinoma (OPSCC), is a major global health challenge due to its increasing incidence and high mortality rate. This study investigates the role of aldo-keto reductase 1C2 (AKR1C2) in OPSCC, focusing on its expression, correlation with Human Papillomavirus (HPV) status, oxidative stress status, and clinical outcomes, with an emphasis on sex-specific differences. We analyzed AKR1C2 expression using immunohistochemistry in formalin-fixed, paraffin-embedded tissue samples from 51 OPSCC patients. Additionally, we performed RT-qPCR in cultured HPV16-E6*I and HPV16-E6 overexpressing HEK293 cell lines (p53WT). Statistical analyses were performed to assess the correlation between AKR1C2 expression and patient data. Our results indicate a significant association between increased AKR1C2 expression and higher AJCC classification (p = 0.009) as well as positive HPV status (p = 0.008). Prognostic implications of AKR1C2 varied by sex, whereby female patients with high AKR1C2 expression had better overall survival, whereas male patients exhibited poorer outcomes. Additionally, AKR1C2 expression was linked to HPV status, suggesting a potential HPV-specific regulatory mechanism. These findings underscore the complex interplay among AKR1C2, HPV, and patient sex, highlighting the need for personalized treatment strategies for OPSCC. Targeted inhibition of AKR1C2, considering sex-specific differences, may enhance therapeutic outcomes. Future research should investigate these mechanisms to enhance treatment efficacy. [ABSTRACT FROM AUTHOR]

Simple Summary: Peritoneal carcinomatosis is a term for cancer cells spreading from tumors of internal organs and massively invading a large part of the membrane lining the abdomen and pelvis. For most patients, peritoneal carcinomatosis suggests only several months of life left. Current medicine can offer only alleviation of symptoms from this incurable disease. Researchers are intensely exploring some new therapeutic targets. Among promising candidates are non-coding RNAs, short molecules serving as important regulators in cells. When a disease such as cancer develops in the body, it is accompanied by typical changes in levels of non-coding RNAs. In this review, we provide an overview of current state of knowledge regarding the changes of non-coding RNA levels in peritoneal carcinomatosis. Deeper understanding of this topic could lead to the identification of non-coding RNAs as feasible specific biomarkers or novel therapeutic targets in the treatment of peritoneal carcinomatosis. Peritoneal carcinomatosis represents an advanced stage of tumors within the peritoneal cavity. Once considered an incurable terminal cancer metastasis, contemporary medicine is on the hunt for certain potentially curative options alongside the present day's palliative disease management. However, for most patients, peritoneal carcinomatosis continues to pose a fatal late-stage prognosis with a grim future outlook. Over the past two decades, non-coding RNAs have garnered significant attention due to their undeniable significance in regulating cellular processes across all levels. Disruption of the intricate regulation led by non-coding RNAs has been demonstrated to have a substantial impact on various human diseases, particularly in cancer, including solid tumors originating from the organs of the peritoneal cavity. This review aims to offer a comprehensive overview of the current state of knowledge in the under-researched field of peritoneal carcinomatosis, focusing specifically on the role of non-coding RNAs in the development of this condition and delineating potential avenues for future research. [ABSTRACT FROM AUTHOR]