Curative resection is typically recommended for treating gastrointestinal stromal tumors (GISTs). Exceptions are made for locally advanced GISTs (LAGISTs) where radical resection may be impossible. First-line imatinib therapy can be employed to treat GISTs harboring mutations in the tyrosine-protein kinase KIT (KIT) and platelet-derived growth factor receptor α (PDGFRα) genes to reduce the tumor size to resectable levels and minimize surgical risks. The present study investigated the treatment outcomes of patients with LAGISTs with different KIT and PDGFRα gene mutations who received first-line imatinib therapy. A total of 37 patients with LAGISTs who underwent first-line imatinib treatment were included, and the median follow-up period was 41 months. Treatment regimens included imatinib, with subsequent therapies, such as sunitinib and regorafenib, administered upon imatinib failure. The genetic profiles of KIT and PDGFRα were analyzed. Of the 37 patients, 24 (64.9%) successfully underwent curative resection. The median progression-free survival (PFS) was 36 months and the median overall survival (OS) was 41 months. Patients presented with tumors with various genetic mutations, which differentially affected their PFS and OS and adverse events were typically manageable. However, the gene mutation status was not significantly associated with treatment response or surgical resectability (both P>0.05). The present study elucidated the effects of first-line therapy on LAGISTs with genetic mutations, underscoring the effectiveness of imatinib treatment and the value of continual patient monitoring. Additional studies with long-term follow-up are required to evaluate treatment outcomes.

Patients with peritoneal metastasis from gastric cancer show poor prognosis with standard systemic chemotherapy. This prospective multicenter phase II clinical trial was performed to evaluate the efficacy and safety of intraperitoneal paclitaxel combined with systemic S-1 plus oxaliplatin for patients with advanced or recurrent gastric cancer with peritoneal metastasis.

Patients with advanced or recurrent gastric cancer with histologically or radiologically confirmed peritoneal metastases were eligible for the study. The chemotherapy regimen consisted of eight cycles of intraperitoneal paclitaxel 80 mg/m2 on days 1 and 8, combined with 80 mg/m2 S-1 for days 1-14, and 100 mg/m2 oxaliplatin on day 1, repeated every 21 days. The primary endpoint was 6-month progression-free survival. One-year progression-free and overall survival, response rate, and safety were set as the secondary endpoints.

In total, 28 patients were included in the study, of which 24 were analyzed, with the exception of those lost to follow-up and withdrawal of consent. The 6-months progression-free survival was 82.6 % (95 % CI: 68.5-99.6 %). The one-year progression-free and overall survival rates were 69.6 % (95 % CI: 53.1-91.2 %) and 76.9 % (95 % CI: 61-97 %), respectively. The overall response rate was 41.67 %. The hematologic toxicity profile showed grade 3/4 hematologic toxicities such as leukopenia (20.8 %), neutropenia (41.7 %), and thrombocytopenia (8.3 %). The only non-hematologic adverse event was grade 3 diarrhea. Three (12.5 %) patients experienced intraperitoneal chemoport-related adverse events.

Bidirectional intraperitoneal paclitaxel with systemic S-1 plus oxaliplatin shows promising efficacy and safety in the treatment of peritoneal metastatic gastric cancer.

Based on the results of KEYNOTE-048 (NCT02358031), first-line standard-of-care treatment for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) includes pembrolizumab alone or with platinum and fluorouracil (5-FU). Results from the single-arm KEYNOTE-B10 (NCT04489888) showed promising antitumor activity and a manageable safety profile offering an alternative pembrolizumab and chemotherapy regimen (KN-B10), with paclitaxel replacing 5-FU. With KEYNOTE-B10 being a non-comparative trial, this study aims to estimate the comparative efficacy of KN-B10 versus alternative first-line systemic treatments for R/M HNSCC via an indirect treatment comparison analysis.

A systematic literature review (October 2023) identified six connected randomized controlled trials with similar eligibility criteria to KEYNOTE-B10. Interventions included cetuximab + platinum + 5-FU (EXTREME), cetuximab + cisplatin + docetaxel (TPEx), pembrolizumab + platinum + 5-FU (KN-048), platinum + 5-FU, cisplatin + paclitaxel, cisplatin, 5-FU, and methotrexate. To connect KEYNOTE-B10 to the network, individual patient-level data were weighted to match the population characteristics of the most similar trial in the network (KEYNOTE-048). The comparative efficacy of KN-B10 versus other interventions was estimated via fixed-effect Bayesian network meta-analyses. Due to violations of the proportional-hazards assumption, fractional polynomials were used to model overall survival (OS) and progression-free survival (PFS).

For objective response, KN-B10 was comparable to EXTREME and TPEx and more efficacious than all other identified treatments (range of odds ratios [ORs]: 1.69-11.75), including KN-048 (OR: 1.69; 95% credible interval: 1.01-2.81). For OS and PFS, KN-B10 was comparable to EXTREME (with improvements in OS after month 12), TPEx, and KN-048. KN-B10 improved OS versus platinum + 5-FU (range of time-varying hazard ratios: 0.60-0.18; months 9-60), cisplatin + paclitaxel (0.53-0.24; 9-36), cisplatin (0.59-0.32; 6-24), 5-FU (0.58-0.20; 6-36), and methotrexate (0.61-0.07; 6-60). KN-B10 improved PFS versus platinum + 5-FU (0.60-0.31; 3-36).

The improved or comparable efficacy of KN-B10 versus alternative first-line interventions in terms of relevant clinical outcomes, as shown in this study, supports its recommendations for the treatment of R/M HNSCC.

Achieving complete response (CR) is a desirable goal in early-to-intermediate-stage hepatocellular carcinoma (HCC). While systemic and locoregional therapies show promise, optimal drug discontinuation criteria remain unclear. This study aims to investigate drug-off criteria for atezolizumab plus bevacizumab as a proof-of-concept study.

This retrospective multicenter study included child-pugh class A patients with unresectable HCC without extrahepatic spread or macrovascular invasion who received atezolizumab plus bevacizumab as first-line therapy. Modified clinical CR (mCCR) was defined as CR per mRECIST with sustained normal alpha-fetoprotein (AFP) levels (< 10.0 ng/dl). Recurrence-free survival (RFS) and overall survival (OS) were analyzed based on the "drug-off" criteria defined by following: (1) mRECIST CR with locoregional therapies, (2) sustained normalization of AFP/AFP-L3/ des-gamma-carboxy prothrombin (DCP) for 12-24 weeks, and (3) complete tumor vascularity disappearance by contrast-enhanced ultrasonography (CEUS) or pathological curative resection.

The median follow-up was 16.5 months (95% CI 15.2-17.8). Among 51 patients achieving mCCR, 11 underwent surgery, with pathological CR in three cases. In contrast, viable lesions were observed in 7 of 40 cases assessed using CEUS. All patients meeting the drug-off criteria (n = 9) showed no recurrence and none of them experienced mortality, while 45.2% (19/42) of those not meeting the criteria experienced recurrence (median RFS: 12.8 months, p = 0.007). The median OS was not reached in dug-off criteria met patients (n = 9), 37.7 months (95% CI: NA) in non-criteria met patients (n = 42), and 27.1 months (95% CI 16.7-37.6) in non-mCCR patients (n = 184) (p < 0.001).

In patients with unresectable and TACE-unsuitable early-to-intermediate-stage HCC who met the drug-off criteria, significantly improved RFS and OS were observed compared those who did not meet the criteria. However, further validation studies are required to confirm the utility of the criteria.

Eribulin can represent a therapeutic alternative for patients with advanced breast cancer who have received at least one or two lines of anthracyclines-based chemotherapy and taxane therapy. In this observational study, we focused on long-responder patients, i.e. with an objective response or stability ≥ 6 months under eribulin to better characterize them.

Metastatic breast cancer (MBC) patients treated by eribulin in 2nd, 3rd or 4th line between September 2011 and June-2018 were included. The following parameters were assessed: primary tumor and metastasis characteristics, type of response and duration, disease progression, treatment received, toxicities, progression free survival (PFS), overall survival (OS), and prognostic factors of OS and PFS. Special attention was paid to patients with hepatic disease (HD).

Among the 98 patients included, an analysis was conducted on 84 patients (median age 62). Median duration of response was 25.6 weeks (95 IC 22-27.7) with a median number of infusions of 6. Response was similar, irrespective of ERI line number. HD was observed in 70.2 % of patients. Median PFS was 9 months (95 %CI 8-10). Subgroup analysis showed similar PFS, irrespective of HD (p = 0.21) and treatment line (p = 0.46). Median OS was 24 months. (95 % IC 20-31). The main prognostic factors of OS were duration of response (p < 0.001) and, progesterone receptor positiveness was associated to PFS (p = 0.006).

This multicentric, retrospective study highlights eribulin as a potential second-line therapy for MBC with a median response duration of 25 weeks after 6 infusions. The safety and efficacy profiles align with previous studies, supporting its role as a viable treatment option. Notably, the response and PFS were independent of hepatic metastasis, suggesting benefit across various MBC subtypes, including those with liver involvement. However, the retrospective design warrants cautious interpretation, and further prospective studies are needed to confirm these findings and optimize eribulin's use, potentially through molecular profiling for personalized treatment strategies.

Neoadjuvant therapy before surgery offers varying benefits as a well-established treatment option for breast cancer. This study specifically evaluated the effectiveness of neoadjuvant endocrine therapy (NET), neoadjuvant chemotherapy (NCT), and neoadjuvant chemo-endocrine therapy (NCET) in patients with estrogen receptor (ER)-positive breast cancer. This meta-analysis was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Electronic searching was conducted to retrieve articles from databases including PubMed, Cochrane Library, EMBASE, CNKI, and Wanfang. The primary outcome measured by odds ratios (ORs) with 95% confidence intervals (CIs) focused on assessing pooled effect sizes. Random-effects or fixed-effect models were conducted according to the existence of statistical heterogeneity. A total of 15 eligible articles were included in the analysis. The results indicated clinical response (CR) (OR = 0.54; 95% CI = 0.41 to 0.73; I 2 = 39.6%) and clinical complete response (cCR) (OR = 0.31; 95% CI = 0.12 to 0.85; I 2 = 68.0%) after NET was significantly higher than NCT. However, no significant difference was shown in pathological complete response (pCR) (OR = 0.49; 95% CI = 0.23 to 1.04; I 2 = 0.0%) and breast-conserving surgery (BCS) (OR = 0.49; 95% CI = 0.23 to 1.04; I 2 = 0.0%). The combined paradigm of NCET presented no significant improvement compared with monotherapy of NET or NCT. Overall, both NET and NCT are effective neoadjuvant treatment options for patients with ER+ breast cancer. More explicit clinical decision indicators need to be further clarified. And NCET does not offer additional benefits over NET or NCT in patients with ER+ breast cancer.

Identifying prognostic markers in colorectal cancer (CRC) is crucial for improving treatment outcomes. Although carcinoembryonic antigen (CEA) is recommended in the guidelines of the National Comprehensive Cancer Network, its sensitivity and specificity are inconsistent, limiting its utility in patients with normal CEA levels. Circulating tumor cells (CTCs), including those expressing CD133-a cancer stem cell marker involved in tumor progression and therapy resistance-are associated with metastasis and survival outcomes. This study evaluated the prognostic significance of CD133-positive CTCs, and their combined effect with CEA, in patients with CRC. Peripheral blood samples from 195 patients with CRC (stages I-IV) were analyzed. CTCs were isolated using OncoQuick tubes and CD133 mRNA expression was detected by reverse transcription polymerase chain reaction. In clinicopathological analysis, CD133-positive CTCs were detected in 27.2% of cases, correlating with serosal invasion (p = 0.016). Multivariate Cox analysis showed that CD133-positive CTCs were associated with worse disease-specific survival (p = 0.001). Patients with CD133-positive CTCs and CEA ≥ 5 ng/mL (high CEA) had a significantly poorer prognosis (p < 0.001), whereas those with CD133-negative CTCs and CEA < 5 ng/mL (low CEA) had a better prognosis (p = 0.039). CD133 expression in CTCs, especially in combination with CEA, may serve as a valuable prognostic marker in CRC.

In neuro-oncological pediatric patients under 3 years of age, chemotherapy intensified to high doses (high-dose chemotherapy, HDC) represents the cornerstone to avoid the potential toxicity of radiotherapy. Combination treatment with gemcitabine-oxaliplatin (GemOx) was administered for infant- type cerebral tumors as a bridge toward autologous hematopoietic transplantation to achieve clinical and neuroradiological permissiveness to HDC and to raise the possibility of second-look neurosurgery.

From May 2017 to May 2023, at Meyer Children's Hospital IRCSS in Florence (Italy), four patients, with a median age of 19 months (with two high- grade gliomas, a metastatic medulloblastoma, and a choroid plexus carcinoma CNS WHO grade 3), were subjected to partial neurosurgical removal and induction therapy delivered according to the Italian program for malignant cerebral tumors under 3 years. To delay HDC, either for disease reassessment or for temporary unfitness, GemOx cycles were administered. Gemcitabine 1,000 mg/m2 and oxaliplatin 100 mg/m2 were given on day 1 every 21-28 days for one to six cycles.

The treatment was well tolerated overall, except for severe platelet hematological toxicity in a patient, which required dose reduction to 75%. After GemOx, one patient was also subjected to further neurosurgery. Bridge therapy made it possible to submit patients to HDC in safety, in permissive clinical conditions, and after assessment of disease stability.

In infant-type cerebral tumors eligible for HDC, GemOx could be a possible strategy in the case of post-induction residual disease to exclude uncertain evolution or when waiting for clinical suitability for second surgery and intensified treatment. The therapy was overall safe and well tolerated. This approach resulted incisive in the therapeutic or palliative choice for extremely young patients with aggressive brain tumors.

Head and neck squamous cell carcinomas (HNSCCs) frequently harbor alterations in the PI3K signalling axis and, particularly, in the PIK3CA gene. The promising rationale of using PI3K inhibitors for the treatment of HNSCC has, however, clashed with the spontaneous development of resistance over time.

To identify valuable targets for overcoming acquired resistance to PI3Kα inhibitors in HNSCC, we performed microRNA profiling on a cohort of HNSCC PDXs that were treated with alpelisib, including both responsive and resistant tumors. Using CRISPR/Cas9, siRNA, and PTEN-/- isogenic and alpelisib-resistant cell models, we examined the role of PTEN in resistance acquisition. Phospho-proteomic analysis identified PTEN-dependent phosphorylation events, while PI3Kα inhibitor-resistant organoids were used to assess PLK1 inhibitor efficacy.

We identified microRNAs altered in resistant PDXs, including members of the miR-17-92 cluster. Mechanistically, we observed that the hyperactive c-Myc was recruited to MIR17HG regulatory regions in alpelisib-resistant cells, sustaining miR-17-5p, miR-19b-3p, and miR-20a-5p expression, which downregulated PTEN. PTEN knockout or depletion conferred alpelisib resistance in HNSCC cells. We identified PTEN-dependent phosphorylation events, such as p-PLK1-T210, involved in resistance. Interestingly, pharmacological inhibition of PLK1 strongly reduced the viability of PI3Kα-resistant organoids derived from HNSCC PDXs and cell line models.

Overall, this study unveils a novel, microRNA-driven, non-genetic mechanism contributing to acquired resistance to PI3Kα inhibitors in HNSCC. Indeed, linking hyperactive c-Myc to sustain miR-17-92 expression and consequent PTEN downregulation, we also propose that targeting PTEN-dependent downstream effectors, such as PLK1, may offer a powerful therapeutic strategy for resistant HNSCC.

Previous studies in multiple metastatic tumors treated with diverse anticancer agents including immunotherapy, chemotherapy, mAb, and TKIs have suggested the rate of tumor growth (g-score) is inversely associated with survival.

We performed a retrospective analysis of patients with metastatic breast cancer (mBC) treated with trastuzumab deruxtecan (T-DXd), ado-trastuzumab emtansine (T-DM1), or chemotherapy to investigate the impact of those therapies on g-score and explore the association of g-score with clinical outcomes. This is the first report assessing g-score in tumors treated with an ADC.

We investigated the association of g-score with progression-free (PFS) and overall survival (OS) in 2 phase 3 studies in patients with HER2 + mBC (DESTINY-Breast03 (DB-03)) and HER2-low mBC (DESTINY-Breast04 (DB-04)). After grouping patients according to quartiles of g-scores, we explored the association between g-score and PFS/OS using Kaplan-Meier plots and Cox regression models. The median g-score was higher for T-DM1, suggesting a faster growth rate at 0.0009/day vs that for T-DXd at 0.0002/day (P < .0001). Additionally, with data collection stopped at the time of database lock, 23% and 48% of tumors demonstrated only regression without growth in the T-DM1 and T-DXd arms, respectively. In DB-04, median g was 0.0018/day and 0.0006/day (P < .0001); with 17% and 32% of tumors demonstrating only regression with treatment of physician's choice (TPC) and T-DXd, respectively.

Compared to T-DM1 and TPC therapies, T-DXd significantly reduced the rate of tumor growth in the overall population and across subgroups. In both studies, the tumor growth rate was inversely associated with PFS and OS. In addition, it showed improved concordance with survival compared to ORR. The use of tumor growth rate as an intermediate endpoint may potentially accelerate drug development and reduce a patient's exposure to agents with limited or no activity.

peptide receptor radionuclide therapy with 177Lu-DOTATATE has become an established second-line treatment for patients with advanced small intestine neuroendocrine tumors (siNET). Treatment efficacy is assessed several months after the end of treatment and is based on RECIST criteria. Post-therapy scintigraphy (PTS) can be performed after each cycle, but its value in early response assessment is debated particularly given the lack of quantification available in clinical routine. New quantification modules are now available, enabling automatic SUV calculation. The main goal of this study is to assess the value of the evolution of SUV between the first (C1) and the second (C2) cycle on quantitative PTS in predicting response to treatment. All patients with siNET referred to our center for treatment with 177Lu-DOTATATE were included. The SUVmax of the lesion with the greatest uptake was measured on PTS SPECT/CT at C1 and C2. ∆SUVmax was calculated. Linear regression between ∆SUVmax and 6-month RECIST percentage was used. Relative changes in tumor metabolic volume (MTV) were also studied along with clinical parameters.

twelve consecutive patients with progressive metastatic siNET were included. One patient showed partial response at 6 months, the other were considered as stable disease. Linear regression showed that 6-month RECIST percentage and ∆SUVmax were strongly correlated with the following regression formula: 6-month RECIST = -0.05 + 0.36 x ∆SUVmax (p < 0.001). ∆MTV was not predictive of response.

we report a significant link between PTS ∆SUVmax and 6-month RECIST percentage in patients with siNET. Quantitative imaging would thus enable the prediction of 6-month response of 177Lu-DOTATATE as early as C2. These results need to be confirmed on a larger population.

Purpose To evaluate two automated tools for detecting lesions on fluorine 18 (18F) fluoroestradiol (FES) PET/CT images and assess concordance of 18F-FES PET/CT with standard diagnostic CT and/or 18F fluorodeoxyglucose (FDG) PET/CT in patients with breast cancer. Materials and Methods This retrospective analysis of a prospective study included participants with breast cancer who underwent 18F-FES PET/CT examinations (n = 52), 18F-FDG PET/CT examinations (n = 13 of 52), and diagnostic CT examinations (n = 37 of 52). A convolutional neural network was trained for lesion detection using manually contoured lesions. Concordance in lesions labeled by a nuclear medicine physician between 18F-FES and 18F-FDG PET/CT and between 18F-FES PET/CT and diagnostic CT was assessed using an automated software medical device. Lesion detection performance was evaluated using sensitivity and false positives per participant. Wilcoxon tests were used for statistical comparisons. Results The study included 52 participants. The lesion detection algorithm achieved a median sensitivity of 62% with 0 false positives per participant. Compared with sensitivity in overall lesion detection, the sensitivity was higher for detection of high-uptake lesions (maximum standardized uptake value > 1.5, P = .002) and similar for detection of large lesions (volume > 0.5 cm3, P = .15). The artificial intelligence (AI) lesion detection tool was combined with a standardized uptake value threshold to demonstrate a fully automated method of labeling patients as having FES-avid metastases. Additionally, automated concordance analysis showed that 17 of 25 participants (68%) had over half of the detected lesions across two modalities present on 18F-FES PET/CT images. Conclusion An AI model was trained to detect lesions on 18F-FES PET/CT images and an automated concordance tool measured heterogeneity between 18F-FES PET/CT and standard-of-care imaging. Keywords: Molecular Imaging-Cancer, Neural Networks, PET/CT, Breast, Computer Applications-General (Informatics), Segmentation, 18F-FES PET, Metastatic Breast Cancer, Lesion Detection, Artificial Intelligence, Lesion Matching Supplemental material is available for this article. Clinical Trials Identifier: NCT04883814 Published under a CC BY 4.0 license.

Purpose: To evaluate the use of yttrium-90 (90Y) dosimetry in predicting treatment outcomes when used following transarterial radioembolization with SIR-Spheres® (Resin 90Y) in patients with hepatic tumors. Materials and Methods: This single institution retrospective analysis included 100 patients with hepatocellular carcinoma, colorectal carcinoma or other liver metastases who underwent transarterial radioembolization with resin 90Y and had imaging follow-up within one year of treatment. Mean tumor dose and mean dose to nontumor was calculated using voxel-based dosimetry software. Descriptive statistics were reported and methods of analyses included simple and multivariable linear regression, contingency table analyses, Kaplan-Meier estimation, and Cox proportional hazards models. Results: Of 100 patients included, 65 demonstrated tumor shrinkage following transarterial radioembolization. Of these, 20 (30.8%) had hepatocellular carcinoma, 22 (33.8%) had colorectal carcinoma, and 23 (35.4%) had other types of metastases. There was an association between tumor shrinkage and mean tumor dose (p = 0.0285) and mean dose to nontumor (p = 0.0028) in hepatocellular carcinoma patients, but not colorectal carcinoma, or the other subgroup. For all 100 patients, time to death and mean tumor dose was associated only in the other subgroup (p = 0.0260), but not in the hepatocellular or colorectal carcinoma groups. Time to death and mean dose to nontumor was associated in hepatocellular carcinoma patients (p = 0.0421), but not the colorectal carcinoma or other subgroup. Conclusions: Voxel-based dosimetry assessment is a tool that may be utilized to assist in predicting treatment outcomes in responders to transarterial radioembolization.

We aim to report on somatostatin receptor (SSTR)-targeted molecular imaging and therapy in patients with advanced esthesioneuroblastoma (ENB).

Five patients with ENB [Kadish stage D in 5/5 (100%); Hyams grade 2 in 2/5 (40%), grade 3 in 2/5 (40%), undetermined in 1/5 (20%)] underwent SSTR-directed PET/CT. We quantified SSTR-avid tumor volume (TV), maximum SUV (SUV max ), and target-to-background ratios (TBR). Based on imaging, peptide receptor radionuclide therapy (PRRT) along with dosimetry was also conducted. We recorded nephrotoxicity and hematotoxicity, including estimated glomerular filtration rate (eGFR), hemoglobin, leukocytes, and thrombocytes at baseline and after the last treatment cycle. We determined adverse events following Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Response and progression-free survival (PFS) was also evaluated.

All 5 patients were rated positive on SSTR-PET/CT. On a lesion-based level, we identified 32 SSTR-avid tumor sites with a median TV of 11.7±10.8 and SUV max of 24.3±12.8. TBR was 19.8±9.7, indicating excellent image contrast. After median 4 (range, 2-6) cycles with a median of 7.7 GBq per cycle per patient, we observed no CTCAE grade 3 or 4 toxicity for leukocytes and thrombocytes and no significant CTCAE events for renal function. One patient (20%), however, developed reversible grade 3 anemia. Up to 11.8 Gy in tumor lesions were achieved. Partial response was recorded in 3/5 (60%), stable disease in 1/5 (20%), and progressive disease in 1/5 (20%). The median PFS was 29 weeks.

SSTR-directed PET provided high image contrast in ENB, suggesting good read-out capabilities in this tumor type. PRRT was also feasible, along with an acceptable safety profile, thereby rendering SSTR-targeted theranostics a potential treatment option in advanced disease.

In many solid tumors, early tumor shrinkage predicts the durability of treatment response. It is unclear whether this is the case for neuroendocrine tumors treated with peptide receptor radionuclide therapy (PRRT).

Data from the phase III NETTER-1 study of [177Lu]Lu-DOTA-TATE (177Lu-DOTATATE) for the treatment of advanced, well-differentiated, midgut NETs were used to investigate whether objective tumor shrinkage (local review) with 177Lu-DOTATATE is associated with progression-free survival (PFS) and overall survival (OS) duration.

Overall, 117 patients were treated with 177Lu-DOTATATE (four cycles of 7.4 GBq every 8 weeks). In a landmark analysis, best tumor shrinkage from baseline until data cut-off (prior to first progression) was not associated with PFS (n = 102; hazard ratio: 1.002 [95% confidence interval (CI): 0.99-1.02]; nominal p = 0.7808). In further ad hoc analyses, patients on the 177Lu-DOTATATE arm were dichotomized into ≥ 30% tumor shrinkage from baseline (18/117 [15.4%]) and < 30% shrinkage (99/117 [84.6%]). Median (95% CI) PFS was 17.6 (16.5-30.3) months in the ≥ 30% shrinkage group and 25.0 (19.4-31.0) months in the < 30% group. OS was not significantly different for the two tumor shrinkage groups (not estimable [31.0 months-not estimable] and 44.3 [34.9-53.8] months, respectively).

These results suggest the benefit of PRRT and the potential PFS and OS benefit of 177Lu-DOTATATE should not be based on tumor shrinkage (objective response versus stable disease) and that lack of tumor shrinkage should not impact application of the approved four cycles of 177Lu-DOTATATE.

The combination of cyclin-dependent kinases 4 and 6 inhibitors (CDK4/6i) with endocrine therapy (ET) has emerged as an effective alternative to neoadjuvant chemotherapy (NCT) for patients with hormone receptor-positive (HR+) and human epidermal growth factor receptor 2 (HER2) -negative breast cancer (BC). This single-center study retrospectively evaluated the efficacy and safety of dalpiciclib combined with an aromatase inhibitor (AI) compared to NCT.

The clinicopathological data and treatment details of patients with HR+ HER2 negative BC who underwent either neoadjuvant endocrine therapy (NET) or NCT were collected from the Fourth Hospital of Hebei Medical University. The primary endpoint of the study was the Residual Cancer Burden (RCB), while secondary endpoints included breast pathological complete response (bpCR), clinical response rates (ORR), proliferation markers, and safety profiles.

Between May 2022 and June 2023, a total of 36 patients were treated with dalpiciclib plus AI, while 137 patients received NCT for the final analysis. Prior to propensity score matching (PSM), the rates of RCB 0 were 0% in the NET group and 7.3% in the NCT group (p=0.205). The rates of bpCR were 2.8% for the NET group and 13.1% for the NCT group (p=0.142). The ORR was comparable between the two groups (p=0.397), as were the rates of BCS (p=0.608). Both treatment groups demonstrated significant reductions in Ki-67 levels, although the extent of reduction was similar (p=0.174). Notably, a Ki-67 level of ≤ 10% post-treatment was more prevalent in the NET group (p<0.0001). Only two patients in the NET group achieved a Preoperative Endocrine Prognostic Index (PEPI) 0 score. The incidence of grade 3-4 toxicities was significantly higher in the NCT group compared to the NET group (p<0.05). Following PSM, patients treated with dalpiciclib plus AI exhibited comparable clinical responses and a safety advantage relative to those receiving NCT.

This study indicates that the combination of dalpiciclib and AI elicits comparable responses and demonstrates improved safety profiles when compared to NCT in patients with HR+ HER2 negative breast tumors. Furthermore, RCB and pCR may not serve as optimal endpoints for evaluating the efficacy of CDK4/6i-based NET.

Preserving health-related quality of life is an aspect of care that requires constant attention from the time of cancer diagnosis. Melatonin has been used to diminish treatment-related side effects and cancer symptoms, and as a medication to regulate circadian rhythm. An up-to-date systematic review is needed to investigate the current evidence concerning possible beneficial effects of melatonin on quality of life and sleep in cancer patients.

To evaluate the benefits and harms of melatonin for preserving health-related quality of life and sleep in cancer patients.

To identify studies for inclusion in this review, we used CENTRAL, MEDLINE, 10 other databases, and four trial registers, together with reference checking, citation searching, and contact with study authors. The latest search date was 10 September 2024.

We included randomised controlled trials (RCTs) of adults (18 years or over) with histologically proven cancer of any stage that evaluated melatonin (alone or in combination with standard anticancer treatment) versus no treatment or placebo (alone or in combination with standard anticancer treatment), or standard anticancer treatment. Standard anticancer treatment refers to treatments to stop or prevent cancer, including chemotherapy, radiation therapy, surgery, immunotherapy, and hormonal therapies (such as androgen deprivation therapy).

The primary outcomes of interest were quality of life and sleep quality within three months, and melatonin-related adverse events. Other outcomes included survival, disease-free survival, progression-free survival, tumour response, and anticancer treatment-related harms.

We used Cochrane's risk of bias tool (RoB 1) to assess the risk of bias in the studies included in the review.

We synthesised results for each outcome using random-effects meta-analysis. The effect size was presented as risk ratio (RR) for dichotomous data and mean difference (MD) for continuous data, with 95% confidence intervals (CI). If this was not possible, due to the nature of the data, we synthesised results in a narrative format. We used GRADE to assess the certainty of evidence for each outcome.

We identified 30 RCTs (reported in 49 publications) involving 5093 adult participants with cancer (2470 males, 2228 females, 395 not reported). Studies were conducted in a hospital setting and took place in at least 10 countries. We assessed two studies at low risk of bias and the other 28 at high risk of bias.

Melatonin plus standard treatment versus placebo plus standard treatment The evidence is very uncertain about the effect of melatonin on quality of life score (MD 2.60, 95% CI -14.53 to 19.73; 1 study, 126 participants; very low certainty evidence), and sleep score (MD 2.80, 95% CI 0.18 to 5.42; 1 study, 50 participants; very low certainty evidence) within three months. We are also very uncertain about potential adverse effects of melatonin: headache (RR 2.77, 95% CI 0.33 to 23.14; 1 study, 25 participants; very low certainty evidence); fatigue (RR 1.02, 95% CI 0.90 to 1.17; 2 studies, 170 participants; very low certainty evidence); and nausea (RR 1.01, 95% CI 0.66 to 1.56; 1 study, 146 participants; very low certainty evidence). No data are available relating to dizziness. We downgraded the certainty of the evidence because of high risk of bias, small sample size, the width of the 95% confidence interval, and indirectness due to inadequate reporting of cancer type. Melatonin plus standard treatment versus standard treatment No data are available relating to quality of life and sleep within three months. The evidence is very uncertain about headaches (experienced by 15 of 820 participants in melatonin groups, with no data available for control groups; 2 studies, 1640 participants; very low certainty evidence). Melatonin likely reduces the incidence of fatigue (RR 0.46, 95% CI 0.39 to 0.55; 10 studies, 1359 participants; moderate-certainty evidence) and may reduce nausea (RR 0.85, 95% CI 0.72 to 1.00; 6 studies, 710 participants; low-certainty evidence). No data are available relating to dizziness. We downgraded the certainty of the evidence because of the high risk of bias and the width of the 95% confidence interval. Melatonin (topical use) plus standard treatment versus placebo plus standard treatment The evidence is very uncertain about the effect of melatonin on quality of life (one study reported no difference between groups, both having the same median score of 66.7; 48 participants; very low certainty evidence). No data are available relating to sleep and adverse events (including headache, dizziness, fatigue, and nausea). We downgraded the certainty of the evidence because of the high risk of bias, small sample size, and insufficient data.

The available evidence is of very low certainty, so we are unable to draw conclusions about the effects of melatonin on quality of life and sleep at three months in people receiving treatment for cancer. There may be no difference in adverse events between melatonin plus standard treatment and placebo plus standard treatment, but the evidence is very uncertain. Data were lacking for some outcomes, such as dizziness. Melatonin used alongside standard treatment probably reduces the risk of fatigue and may reduce nausea when compared to standard treatment alone. Since the evidence base for melatonin in people with cancer is limited due to insufficient data and risks of bias in study design, the decision for or against using melatonin as an adjunct to cancer treatment cannot easily be made at the current time.

This Cochrane Review was partially funded by AG Biologische Krebstherapie, Deutsche Krebshilfe (grant numbers 70-301 and 109863). The funding agency had no role in the design or conduct of the study.

The protocol for this review is available via DOI 10.1002/14651858.CD010145.

Locoregional treatments for early-stage unresectable hepatocellular carcinoma (HCC) are widely used, with irreversible electroporation (IRE) and transarterial chemoembolization (TACE) representing two non-thermal treatment options. However, to date, no systematic evaluations of these technologies have been conducted. This study sought to comparatively assess the safety and effectiveness of IRE and TACE for the treatment of very early and early-stage, inoperable HCC via systematic literature reviews (SLRs) and meta-analyses.

Searches were conducted targeting English-language publications and congress proceedings of clinical trials and observational studies from January 1, 2012 to December 21, 2023 that reported effectiveness and safety outcomes (tumor response, progression-free survival (PFS), adverse events (AE)) for IRE and TACE. Two reviewers independently assessed eligibility and abstracted data. For each procedure, meta-analyses were conducted to assess tumor response by follow-up time point, as data permitted, and other outcomes were descriptively analyzed; Quality and risk of bias assessments were performed.

12 IRE publications (195 patients) and 33 TACE publications (6,899 patients) met eligibility criteria. During 0 to < 3 month follow-up, complete response was achieved in 84% of IRE patients vs. 68% for TACE (all results at 1-month); a proportion that increased at 3 to < 6 months (91% IRE vs. 41% TACE). Median PFS was 10.4 months for IRE and 19-30 months for TACE. Serious AEs (SAEs) were experienced by 4% vs. 5% of IRE and TACE patients, respectively.

Both IRE and TACE are safe and effective non-thermal treatments for unresectable, very early and early-stage HCC. The high rate of short-term complete response observed for IRE, coupled with a low SAE rate, may support the broader adoption of this procedure in this patient population.

The relationship between circulating tumor cells (CTCs) and patients with advanced gallbladder adenocarcinoma (aGA) has been rarely studied. This article was to demonstrate the enumeration, classification, and clinical application of CTCs in patients with aGA.

Peripheral blood samples were collected and CTCs were detected using the CanPatrol® technique. T test, χ2 test, Wilcoxon rank sum test or Kruskal-Wallis test, log-rank test and Cox regression analysis were performed to conduct statistical analysis.

CTCs were detected at pre-treatment in 75.00% (27/36) of the patients. Both CTCs positive rate and CTCs enumeration at pre-treatment were significantly associated with clinicopathological parameters including Ca199 level (P = 0.014, P < 0.001 respectively), tumor differentiation (P = 0.007, P = 0.002 respectively), lymph infiltration (P = 0.010, P = 0.025 respectively), vascular infiltration (P = 0.007, P < 0.001 respectively), and distant metastasis (P = 0.015, P = 0.002 respectively). CTCs-positive patients had a significantly shorter OS (HR 0.335, 95% CI 0.165-0.678, P = 0.0023) and PFS (HR 0.364, 95% CI 0.179-0.739, P = 0.0024) than CTCs-negative patients. Mesenchymal CTCs enumeration was closely related to the chemotherapy response, and CTCs programmed cell death ligand-1 (PD-L1) was highly correlated with the immunotherapy response. Positive CTCs at pre-treatment was closely related to the poor OS (HR 0.089, 95% CI 0.020-0.399, P = 0.002) as well as distant metastasis (HR 0.159, 95% CI 0.041-0.610, P = 0.007), untreated with chemotherapy (HR 4.510, 95% CI 1.403-14.499, P = 0.011) and untreated with immunotherapy (HR 6.845, 95% CI 1.894-24.738, P = 0.003).

Pretreatment-positive CTCs was closely related to the poor prognosis in patients with aGA. Monitoring the subtype and phenotype of CTCs may be one of the means to assess tumor treatment response.

Metastatic castration-resistant prostate cancer (mCRPC) has a poor prognosis. This study evaluated the safety, immune responses, and clinical outcomes of Wilms' tumor 1 (WT1) peptide-loaded dendritic cell (DC) vaccination combined with hormone or chemotherapeutic agents in mCRPC patients.

WT1 peptide-loaded mature DCs were administered intradermally and the adjuvant OK-432 every 2-4 weeks. WT1-specific immune responses were assayed using ELISpot, HLA-tetramer, and CD107a assays.

Vaccination was well tolerated with no severe adverse events. WT1-specific immune responses were significantly enhanced in patients with stable disease (SD), along with reduced regulatory T cells. A PSA reduction of >50% was achieved in 35.7% of patients. Median overall survival (mOS) was 28.5 months, exceeding the Halabi nomogram's estimate (19.0 months). Patients with WT1-specific immune responses exhibited significantly longer mOS, suggesting a link between WT1-specific immunity and favorable outcomes.

This immunotherapy approach shows promise for improving survival in mCRPC patients.

Despite significant advances in the treatment of lung cancer (LC), there are no reliable biomarkers to effectively predict therapy response and overall survival (O/S) in non-small cell lung cancer (NSCLC) subtypes. While targeted therapies have improved survival rates in lung adenocarcinoma (LUAD), effective treatment options for lung squamous cell carcinoma (LUSC) are still limited. Recent evidence indicates that exosome-bound WNT5A may significantly contribute to disease progression. Our study assessed the WNT5A protein as a potential biomarker for diagnosing patients and predicting prognosis to assist in therapy selection.

Primary tumor tissue and serum samples were collected from a cohort of 60 patients with histologically confirmed NSCLC before therapy. Healthy serum donors served as controls. Exosomes were isolated, then exosome number and size were measured, and WNT5A protein levels were identified in tissue and in vesicle-free, vesicle-bound fractions of the serum by ELISA.

Extensive statistical analysis (ROC, AUC, Cox, etc.) revealed that elevated WNT5A levels on the serum-exosome surface correlated with distant metastasis, advanced disease stage, and lymph node involvement in LUSC but not in LUAD patients. Moreover, a high WNT5A exosome surface expression was associated with a poor response to therapy and shorter O/S in LUSC patients. Additionally, serum-exosome surface + cargo WNT5A content distinguished LUAD and LUSC subtypes.

WNT5A, particularly its serum exosome-bound form, may serve as a valuable biomarker after further validation for differentiating NSCLC subtypes and predicting disease progression. Importantly, the information can become available from a simple serum sample at the time of diagnosis.

Early detection of major complications and immediate therapeutic interventions may improve patient outcome after hepatectomy. The aim of the present study was to develop a model predicting the risk of postoperative complications after hepatectomy and help identify patients who require close-monitoring in intensive care unit (ICU).

Patients underwent hepatectomy at Humanitas Research Hospital, Italy, between 2010 and 2021 were considered. We used preoperative, intraoperative and combined predictors to build three models predicting Clavien-Dindo III-V complications. Model performances was evaluated internally via bootstrapping.

Of 1497 patients, 7% had Clavien-Dindo III-V complications. Tumor pathology, tumor burden, previous chemotherapy, liver characteristics, clinical portal hypertension, cardiopathy, creatinine and total protein level were incorporated in the preoperative model. In addition to these variables, type of hepatectomy, operation time, additional surgical procedure, and transfusion were incorporated into the combined model. The bootstrap corrected C-indices for preoperative, intraoperative and combined models were 0.68, 0.70 and 0.72. The median predicted probability of major complications over-1000 bootstraps was close to observed probabilities for all models.

These prognostic models may help identify patients at high-risk of major complication and guide decision-making for individual patients and postoperative ICU-care assessment. Observed optimism in model performance necessitates external validation.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and young adults. Typically, treatment involves a multimodal approach, with radiotherapy (RT) being a standard choice alongside surgical resection for local control, particularly in cases harboring fusions involving FOXO1. However, the long-term consequences of offering RT especially to the extremity in children can be significant including growth delay, contracture, arthritis, and secondary malignancy. Herein, we report the outcome of 10 consecutive patients with extremity RMS from two high-volume institutions who did not receive RT to primary site.

Demographic, genetic, tumor characteristics, surgical details, post-resection overall survival and event-free survival data were retrospectively collected from the CanSaRCC (Canadian Sarcoma Research and Clinical Collaboration) database.

Despite the absence of adjuvant RT to the primary tumor site, 90 % of this cohort patients experienced no local failure and the single patient with local failure was subsequently salvaged with RT and further chemotherapy.

By presenting this distinctive real-world data, our aim is to illustrate that in a select high-volume pediatric sarcoma center, extremity RMS can potentially be effectively managed through surgery and chemotherapy alone.

Clinical research paper.

Level IV.

The purpose of this research was to evaluate the effectiveness and safety of neoadjuvant chemotherapy plus radical surgery (NCRS) and concurrent chemoradiotherapy (CCRT) based on three-dimensional conformal radiation therapy (3DCRT) for FIGO 2018 stage IB3/IIA2 patients with cervical squamous cell carcinoma in a resource-limited setting.

The clinical outcomes and incidence of complications in 137 patients who underwent NCRS with those of 163 patients who CCRT based on 3DCRT were compared. Propensity score matching (PSM) analysis was used to match the two groups to enable further statistical comparisons. Survival analysis was performed utilizing Cox proportional hazards regression analyses, Kaplan-Meier curves, and log-rank tests. Furthermore, the incidence of complications between the two groups was also compared using chi-squared tests.

PSM analysis identified 103 matched pairs of patients. The NCRS and CCRT groups exhibited 5-year overall survival (OS) rates of 85.4% and 91.2%, respectively (p=0.19). Additionally, the NCRS and CCRT groups exhibited 5-year disease-free survival (DFS) rates of 76.7% and 89.3% (p=0.02), and the recurrence rates were 20.4% and 9.7% (p=0.03), respectively. However, the CCRT group exhibited a higher incidence of early any-grade complications (79.6% vs 35.9%, p<0.001) and early grade 3 complications (15.5% vs 2.9%, p=0.002) compared to the NCRS group. In terms of overall late complications, there was no significant difference in the incidence between the two groups. Multivariate analysis revealed that stage IIA2 emerged as an independent risk factor for OS (aHR 8.89; p=0.033). Moreover, histologic grade 2-3 (aHR 5.3; p=0.022), stage IIA2 (aHR 2.95; p=0.043), NCRS treatment (aHR 2.41; p=0.012) were identified as independent risk factors for DFS.

In resource-limited settings, for patients with FIGO 2018 stage IB3/IIA2 cervical squamous cell carcinoma, 3DCRT-based CCRT offers superior disease-free survival and reduced recurrence rates compared to NCRS, despite increased early complication rates.

We investigated whether TK1 concentration or activity in the blood, drawn at baseline and under therapy, might have value for therapy management in 110 hormone receptor-positive (HR+), HER2-negative (HER2-) metastatic breast cancer (mBC) patients treated with CDK4/6 inhibitors (CDK4/6i) and/or endocrine therapy (ET). TK1 concentration and activity were not significantly correlated with each other in matched samples. In the CDK4/6i cohort at baseline, high TK1 concentration and activity were significantly associated with a decreased PFS and primary resistance. Longitudinal sampling revealed a higher variability of TK1 concentration under therapy compared to TK1 activity that was reduced during therapy. Elevated TK1 activity after six months of CDK4/6i and an increase in TK1 concentration from baseline to six months under CDK4/6i significantly correlated with a decreased PFS. These results indicate a possible value of TK1 concentration and activity before and during CDK4/6i for HR+/HER2- mBC patients to guide treatment that warrants further investigation.

Carcinoembryonic antigen (CEA) is the only prognostic circulating biomarker used in clinical practice for recurrence free (RFS), progression free (PFS) and overall survival (OS) in patients with colorectal cancer (CRC). Not all CRC tumors express this protein and carbohydrate antigen (CA)19-9 has been proposed as an adjunctive in prognostication. We aimed to test if CA19-9 yielded additional information to CEA regarding prognosis.

We included 886 patients with CRC across eight clinical cohorts. Preoperative serum samples were collected from 376 patients with stage I-III CRC and from 510 with metastatic (m)CRC before 1st (n = 233), 3rd (n = 178) and 3rd/4th (n = 99) line chemotherapy. CA19-9 and CEA were determined by routine assays, the values were log-2 transformed and entered as variables in Cox regression models with RFS (stage I-III), PFS and OS as the outcomes, adjusted for age, sex, and site of primary tumor and mutual adjustment between CA199 and CEA. Random effects meta-analyses were conducted for stage I-III,1st line, and 3rd/4th line mCRC cohorts separately.

Meta-analyses showed that higher pre-treatment CA19-9 and CEA were associated with shorter RFS (CA19-9: hazard ratio per doubling of concentration (HR)=1.20, 95 % confidence interval (CI) 1.05-1.38; CEA: HR=1.22, 95 % CI 1.05-1.41) in stage I-III CRC. Only higher CEA was associated with shorter OS in 1st line mCRC (HR=1.07, 95 % CI 1.00-1.07).

CA19-9 might aid in identifying patients with a high risk of recurrence after primary radical resection. Further studies are needed to validate these findings.

The randomized controlled pivotal phase 3 study evaluated efficacy and safety of neoadjuvant complex biologic, Leukocyte Interleukin Injection (LI), administered for 3 consecutive weeks pre-surgery, in treatment naïve resectable locally advanced primary squamous cell carcinoma of oral cavity and soft palate. Randomization 3:1:3 to LI+/-CIZ (cyclophosphamide, indomethacin, and zinc)+SOC, or SOC (standard of care) alone. LI-treated patients received 400 IU (as interleukin-2 equivalent; 200 IU peritumorally, 200 IU perilymphatically) sequentially, daily 5 days/week for 3 weeks before surgery. All subjects were to receive SOC. Post-surgery, patients with low risk for recurrence were to receive radiotherapy, while those with high risk received concurrent chemoradiotherapy. Median follow-up was 56 months. There were 923 ITT (Intent-to-Treat) subjects (380 ITT low-risk and 467 ITT high-risk). Pre-surgery objective early response (45 objective early responders; 5 complete responses [CRs], 40 partial responses [PRs], confirmed by pathology at surgery. LI (+/- CIZ) had 8.5% objective early responders (45/529 ITT) and 16% objective early responders (34/212 ITT low-risk) vs. no reported SOC objective early responders (0/394 ITT). Objective early responders significantly lowered death rate to 22.2% (ITT LI-treated), 12.5% (ITT low-risk LI + CIZ + SOC), while the ITT low-risk SOC death rate was 48.7%. Thus, objective early response impacted overall survival (OS); proportional hazard ratios were 0.348 (95% CI: 0.152-0.801) for ITT low-risk LI-treated, 0.246 (95% CI: 0.077-0.787) for ITT low-risk LI + CIZ + SOC. ITT low-risk LI + CIZ + SOC demonstrated significant OS advantage vs. ITT low-risk SOC (unstratified log-rank p = 0.048; Cox hazard ratio = 0.68; 95% CI: 0.48-0.95, Wald p = 0.024 [controlling for tumor stage, tumor location, and geographic region]). Absolute OS advantage increased over time for ITT low-risk (LI + CIZ + SOC)-treated vs. ITT low-risk SOC: reaching 14.1% (62.7% vs. 48.6%) at 60 months, with 46.5 months median OS advantage (101.7 months vs. 55.2 months), respectively. Quality of life benefit for complete responders sustained for >3 years post LI treatment. Percent treatment-emergent adverse events were comparable among all treated groups. No excess safety issues were reported for LI over SOC alone post-surgery. NCT01265849, EUDRA:2010-019952-35.

Therapeutic efficacy of KRASG12C(OFF) inhibitors (KRASG12Ci) in KRASG12C-mutant non-small cell lung cancer (NSCLC) varies widely. The activation status of RAS signaling in tumors with KRASG12C mutation remains unclear, as its ability to cycle between the active GTP-bound and inactive GDP-bound states may influence downstream pathway activation and therapeutic responses. We hypothesized that the interaction between RAS and its downstream effector RAF in tumors may serve as indicators of RAS activity, rendering NSCLC tumors with a high degree of RAS engagement and downstream effects more responsive to KRASG12Ci compared with tumors with lower RAS-RAF interactions.

We developed a method for measuring in situ RAS binding to RAF in cancer samples using proximity ligation assays (PLA) designed to detect panRAS-CRAF interactions.

The panRAS-CRAF PLA signal correlated with levels of both RAS-GTP and phosphorylated ERK protein, suggesting that this assay can effectively assess active RAS signaling. We found that elevated panRAS-CRAF PLA signals were associated with increased sensitivity to KRASG12Ci in KRASG12C-mutant NSCLC cell lines, xenograft models, and patient samples. Applying a similar PLA approach to measure the interactions between EGFR and its adapter protein growth factor receptor-bound protein 2 as a surrogate for EGFR activity, we found no relationship between EGFR activity and response to KRASG12Ci in the same samples.

Our study highlights the importance of evaluating in situ RAS-RAF interactions as a potential predictive biomarker for identifying patients with NSCLC most likely to benefit from KRASG12Ci. The PLA developed for quantifying these interactions represents a valuable tool for guiding treatment strategies.

Our study aimed to examine the predictive relevance of the Systemic Immune-Inflammation Index (SII) in patients with metastatic castration-resistant prostate cancer (mCRPC). A total of 113 mCRPC patients were assessed. In this descriptive study, SII was calculated using the formula (neutrophil count × platelet count)/lymphocyte count. The optimal threshold for SII, determined via the ROC curve, was 700. Patients with SII ≤ 700 were classified as SII-low, while those with SII > 700 were categorized as SII-high. The median overall survival (mOS) was significantly longer in the low SII group compared to the high SII group (*P = 0.015). In multivariate analysis, Gleason score, albumin levels, CHAARTED volume, and SII were identified as significant prognostic factors. Our findings indicate that SII has a strong correlation with survival and can serve as an independent prognostic marker in mCRPC patients.

Scientists have been actively investigating novel therapies that can effectively eradicate cancer cells with negligible side effects in normal tissues when used alone or in a combinatorial approach. Photodynamic therapy has emerged as a promising non-invasive therapy that integrates photosensitizer, oxygen, and a specific wavelength of light for the treatment of cancer. Despite encouraging outcomes yielded by PDT, conventional PSs are faced with longstanding challenges such as poor water solubility, a short half-life, and off-target toxicity. Development of nanotherapeutics has shown great potential in overcoming this issue. The tumor microenvironment is inherently hypoxic, and this promotes tumor resistance to PDT, as it is oxygen-dependent. Photoactivated chemotherapy, an oxygen-independent light-based therapy, utilizes chemotherapeutic regimens that remain inert until exposed to light, allowing target-specific activation while minimizing off-target toxicity. Integration of these techniques can improve selectivity and yield synergistic cytotoxic effects that could improve cancer treatment.

The FLOT 4-AIO trial established the docetaxel-based regimen's superiority over epirubicin-based triplet therapy in terms of survival rates and acceptable toxicity for locally advanced resectable gastric (LARGC). Yet, fewer than half of the patients achieved completion of eight prescribed FLOT cycles. We proposed that administering all FLOT cycles in the form of total neoadjuvant therapy may improve completion rates and downstaging. This study contrasted total neoadjuvant therapy (FLOT x8) with standard neoadjuvant therapy (FLOT 4+4) for patients LARGC adenocarcinoma who underwent curative resection with routine D2 lymphadenectomy, focusing on histopathological outcomes, toxicity, and survival outcomes.

We reviewed patients with histologically confirmed advanced clinical stage cT2 or higher, nodal positive stage (cN+), or both, with resectable gastric tumors and no distant metastases (January 2017 to July 2023). We divided patients into two groups, FLOT 4+4 and FLOT x8; FLOT 4+4 patients underwent four preoperative and four postoperative bi-weekly cycles of docetaxel, oxaliplatin, leucovorin, and fluorouracil, while FLOT x8 patients received all eight cycles preoperatively after a gradual practice change starting from January 2020. Propensity score matching adjusted for age, clinical stage, tumor location, and histology.

Of the 77 patients in the FLOT x8 group, 37 were propensity-matched to an equal number in the FLOT 4+4 group. Demographics, duration of surgery, and hospital stay showed no significant differences between the groups. The FLOT x8 group exhibited a significantly higher all-cycle completion rate at 89.1% compared to FLOT 4+4's 67.6% (p < 0.01). Both groups demonstrated comparable hematological and non-hematological toxicity rates, Clavien-Dindo ≥ 3 complications, and CAP tumor regression grades. The mean number of harvested lymph nodes was 42.5 and 41.2 in the FLOT 4+4 and FLOT x8 groups, respectively. Similar rates of disease-free survival and overall survival were noted in both groups, despite a trend toward a higher pathological complete response rate, albeit not statistically significant (8.1% vs. 18.9%, p = 0.29), in the FLOT x8 group at a median follow-up of 36 months.

Total neoadjuvant therapy with the FLOT x8 protocol corresponds to higher treatment completion rates, a safety profile similar to standard perioperative therapy, and a twofold increase in complete pathological response. Further research on long-term oncological outcomes is needed to confirm the effectiveness of total neoadjuvant therapy.