5-year OS Rates Research Articles

Clinical features and prognostic factors of pediatric Langerhans cell histiocytosis: a single-center retrospective study

PurposeTo retrospectively evaluate the clinical features and prognostic factors of pediatric LCH patients treated in a single center of China.MethodsPediatric LCH cases were treated following the SD-LCH protocol at the Affiliated Provincial Hospital of Shandong First Medical University in Jinan, China. An analysis was conducted on 82 recently identified LCH cases to retrospectively evaluate the initial symptoms, therapeutic alternatives, and extended results. Follow-ups were conducted until July 31, 2023.ResultsThe median age at diagnosis was 2 (0.25–12) years. 42 (51.2%) were SS-LCH, and 40 (48.8%) were MS-LCH. The most common organ involved was bone (82.9%). Over the 16-year follow-up period, the 5-year EFS and OS rates were 75.2 ± 5% and 90.9 ± 3.3%, respectively. The cumulative reactivation rate was 23.2%. The 5-year EFS rate in SS-LCH and MS-LCH patients were 90.2 ± 4.6% and 58.8 ± 8.3%, and the 5-year OS rate in SS-LCH and MS-LCH patients were 90.2 ± 4.6% and 81.2 ± 6.5%, respectively. The 5-year OS and EFS rate in RO+ LCH and RO− LCH patients were 79.5 ± 7.5%, 53.8 ± 9.6% and 87.5 ± 11.7%, 76.2 ± 14.8%, insignificantly. Multivariate Cox regression showed that liver involvement predicted poor EFS and hematological system involvement was an independent prognostic factor for OS. Detection of the BRAFV600E mutation and targeted therapy significantly improved the prognosis post-2017.ConclusionLiver or hematological system involvement indicates a poor prognosis, and the SD-LCH protocol improves prognosis for pediatric LCH patients.

Atezolizumab plus bevacizumab in patients with unresectable or metastatic mucosal melanoma: 3-year survival update and multi-omics analysis.

Atezolizumab plus bevacizumab has shown promising efficacy in advanced mucosal melanoma in the multi-centre phase II study. This report updates 3-year survival outcomes and multi-omics analysis to identify potential response biomarkers. Forty-three intention-to-treat (ITT) patients received intravenous administration of atezolizumab and bevacizumab every 3 weeks. Available samples underwent whole exome sequencing, transcriptome sequencing and targeted bisulphite sequencing to assess correlations with clinical outcomes. With a median follow-up of 40.3 months, the median overall survival (mOS) was 23.7 months (95% confidence interval [CI], 15.1-34), and the 3-year OS rate was 28.7% (95% CI, 17.6%-46.8%). Patients with upper site melanoma exhibited longer progression-free survival (PFS), higher tumour neoantigen burden (TNB) and greater copy number variations (CNVs) burden compared to those with lower site melanoma. NRAS mutations were associated with enhanced angiogenesis, with five of six patients achieving partial response. Inflammatory cell infiltration, angiogenic status and activation of the SMAD2 and p38 MAPK pathways may be prognostic indicators. This 3-year updated analysis confirms the sustained efficacy of atezolizumab in combination of bevacizumab in patients with advanced mucosal melanoma. Inflammatory cell infiltration and angiogenic status were associated with therapeutic response. Furthermore, mucosal melanoma of upper site and NRAS mutation appear to be good predictors of response to immune checkpoint inhibitor and anti-angiogenic combination treatment. Targeting SMAD2 and p38 MAPK pathways may further improve the outcome of mucosal melanoma. 3-year follow-up study confirmed the therapeutic efficacy of atezolizumab combined with bevacizumab Tumors in the upper site and NRAS mutations are more sensitive to treatment Inflammatory cell infiltration, angiogenic status, and activation of the SMAD2 and p38 MAPK pathways may be prognostic indicators.

Efficacy and Safety of Three Cycles of TIP and Sequential High Dose Chemotherapy in Patients with Testicular Non-Seminomatous Germ Cell Tumors

Background: Salvage treatment options have not been validated in relapsed or refractory germ cell tumors. Moreover, the study populations including these patients have different heterogeneities. This study aimed to evaluate the efficacy and safety of three cycles of TIP sequential high-dose chemotherapy in patients with testicular non-seminomatous germ cell tumors who relapsed or had a refractory course after first-line platinum-based chemotherapy. Methods: Data of 141 patients who underwent three cycles of TIP followed by HDCT due to relapsed/refractory gonadal NSGCTs after first-line cisplatin-based chemotherapy (BEP/EP) at Gulhane School of Medicine Hospital Medical Oncology Department between January 2017 and May 2024 were evaluated retrospectively. Patients underwent a treatment regimen consisting of two phases. Initially, they received three cycles of induction therapy using a combination known as TIP, which includes paclitaxel, ifosfomide, and cisplatin. Following this, they were given a single cycle of high-dose chemotherapy. Demographic and clinicopathological features of patients and treatment-related complications and survival outcomes were recorded. Results: Median follow-up for all patients was 35.2 (95% CI, 29.45 to 41.07) months. Complete Response (CR) or marker negative Partial Response (PR) after HDCT was achieved in 84 (59.6%) patients. Median time for PFS not reached (NR) (95% CI, NR) in the entire group. The 2-year PFS rate was 51.8%. Median time for OS not reached (95% CI, NR) and the 2-year OS rate was 72.3%. The most common myelotoxicity observed after HDCT until engraftment was grade 4 neutropenia (100%) and grade 4 thrombocytopenia (96.5%). Transplantation-related mortality occurred in 7.1% of patients. Variables that remained statistically significant in multivariable analysis and were associated with poor prognosis for overall survival were platinum refractory disease and AFP and/or beta HCG elevation. Conclusions: Significant survival can be achieved after three cycles of TIP consecutive HDCT, while treatment-related mortality was found to be low.

Efficacy and safety of neoadjuvant S-1-based chemoradiotherapy in resectable and borderline-resectable pancreatic cancer: a long-term follow-up study

Background/objectivesThis study aimed to evaluate the safety, efficacy, and long-term outcomes of S-1-based neoadjuvant chemoradiotherapy (NACRT) in patients with resectable or borderline-resectable pancreatic ductal adenocarcinoma (PDAC).MethodsThis retrospective study included patients with PDAC who underwent S-1-based NACRT at our institute between 2010 and 2017.ResultsForty patients were included in the study, including 15 (37.5%) with resectable PDAC and 25 (62.5%) with borderline-resectable PDAC. The NACRT completion and resection rates were 85.0% (n = 34) and 67.5% (n = 27), respectively. Several grade 3 adverse events were observed, including leukopenia (25.0%), anorexia (17.5%), neutropenia (10.0%), thrombocytopenia (7.5%), febrile neutropenia (2.5%), elevated aspartate aminotransferase/alanine aminotransferase (2.5%) levels, and hyponatremia (2.5%). The R0 resection rate was 70.4% (n = 19/27) in patients who underwent pancreatectomy. Grades 1, 2, and 3 according to the College of American Pathologists grading system were observed in 1 (3.7%), 12 (44.4%), and 14 (51.9%) patients, respectively. Over a median follow-up period of 32.9 months (interquartile range, 9.1–68.0), the 1-, 3-, and 5-year OS rates were 81.4%, 45.5%, and 30.3%, respectively, in the intention-to-treat analysis. In the curative-intent surgery cohort (n = 27), the 1-, 3-, and 5-year OS rates were 88.9%, 48.2%, and 37.0%, respectively.ConclusionsS-1-based NACRT is safe and yields acceptable long-term outcomes for patients with resectable or borderline-resectable PDAC.

Effectiveness of neoadjuvant chemotherapy with a docetaxel, cisplatin, and S-1 (DCS) regimen for T4b gastric cancer

BackgroundNo studies on neoadjuvant chemotherapy for gastric cancer (GC) with T4b stage were reported. This study aimed to assess the effectiveness of neoadjuvant chemotherapy using DCS regimen (docetaxel, cisplatin, and S-1) for GC with T4b stage.MethodsForty-three patients diagnosed GC with surgical or clinical T4b stage received three or four preoperative cycles of DCS therapy followed by gastrectomy and lymphadenectomy between Jan-2018 and Dec-2022. Short-tern outcomes including tumor response, completion of neoadjuvant chemotherapy, toxicity and adverse events, rate of treatment-related death, R0 resection, rate of complete adjuvant chemotherapy and short-term surgical results were investigated. The oncologic outcomes comprised 3-year OS and 3-year disease-free survival (DFS).ResultsA total of 43 patients with T4b gastric cancer were included in the analysis. Among them, twenty-five patients underwent gastrectomy and lymphadenectomy. The completion rate of neoadjuvant chemotherapy was 88.4%, including 4 cycles of 51.2% and 3 cycles of 37.2%. The disease-control and clinical response rate were 88.4% and 58.1%, respectively. During preoperative chemotherapy, grade 3/4 neutropenia occurred in 20.9%, anemia in 13.9%, hyponatremia in 4.8%, and vomiting in 2.3%. Pathologic complete response was achieved in 8.0%. After surgery, no patient experienced severe complications (Clavien Dindo > = 3). The R0 resection rate was 72.0% and the rate of complete adjuvant chemotherapy was 83.3%. The 3-year OS and DFS rates were 49% and 38%, respectively.ConclusionsNeoadjuvant chemotherapy with DCS regimen demonstrated a high tolerance, high tumor response rate, high complete adjuvant chemotherapy rate and satisfactory 3-year survival outcomes. Three- or four-course of preoperative DCS regimen is a promising approach for GC with T4b stage.

Radiation-induced nasopharyngeal necrosis combined with local recurrence in nasopharyngeal carcinoma: diagnosis and treatment strategies

ABSTRACT Background To identify the diagnosis and treatment strategies by analyzing the clinical characteristics and treatment methods of RNNCLR. Methods A total of 210 patients pathologically diagnosed with RNNCLR were retrospectively included. Clinical characteristics, MRI features, treatment methods, and survival outcomes were analyzed. Propensity score matching (PSM) analysis was performed to adjust the surgical benefit. Results Ninety-one patients (43.3%) took a single biopsy, 67 patients (31.9%) underwent repeated biopsies and 52 patients (24.8%) received endoscopic surgery to obtain pathological positive tissues. RNNCLR had characteristic imaging features distinguished from pure radiation necrosis. The interval from the previous radiotherapy was 13.2 (7.0, 23.3) months. The 1-year, 3-year, and 5-year overall survival rates were 59.6%, 32.3%, and 14.6%. Patients with reirradiation, detectable EBV-DNA level, or ICA exposure had a worse prognosis. Overall survival was significantly higher in the endoscopic surgery group than in nonsurgery group after PSM (3-year OS rates, 44.5% vs. 23.9%, p = 0.011). Conclusions Histopathological diagnosis of RNNCLR needs repeated biopsies or even surgery. Careful analysis of MRI images, correlation with interval time from last radiation, and short-term follow-up may solve the diagnostic dilemmas. Endoscopic surgery results in a survival benefit by completely resecting lesions or removing necrotic tissue to reduce necrosis-related complications.

Impact of neck dissection in cN0 patients undergoing primary or salvage total laryngectomy.

It is debatable whether neck dissection is necessary in patients with advanced laryngeal carcinoma who are clinically node-negative (cN0). We assessed the effect of neck dissection on overall survival in patients with cN0 undergoing primary or salvage laryngectomy. A retrospective evaluation of cN0 patients who underwent primary or salvage total/pharyngolaryngectomy at a French tertiary facility in 2008-2018, with or without neck dissection, was carried out. Patients were divided into two groups: primary (n = 65) and salvage (n = 84). Comparing subglottic (HR = 3.978; p = 0.023) and hypopharyngeal (HR = 2.958; p = 0.018) malignancies to other tumor subsites, the mortality rates were greater. The primary group had a greater rate of occult metastases (23.07% vs. 14.28%; p = 0.089) than the salvage. The average lymph node ratio was significantly different between the treatment groups (0.05 ± 0.04 vs. 0.17 ± 0.33; p = 0.004). If LNR > 0.05, we found poor survival rates (p < 0.001). Although performing a neck dissection during the primary treatment increased the 5-year OS rate (Yes 89.5% vs. No 83.3%; p = 0.062), there was no discernible difference in the salvage group (Yes 80.3% vs. No 78.6%; p = 0.806; Log-rank p > 0.05). For the predicted survival variables, no significant relationships were detected in the Cox regression analysis (all p-values > 0.05). Although the primary group had a greater frequency of occult metastases, neither the primary group's survival outcomes nor those of the salvage laryngectomy cases were significantly affected by neck dissection. LNR and the location of the tumor were important variables that could affect survival and the choice to do a neck dissection.

Treatment of metastatic breast cancer by stereotactic body radiotherapy (SBRT) and stereotactic radiosurgery (SRS)

Background and purposeThe role of local ablative radiotherapy (stereotactic body radiotherapy (SBRT)/stereotactic radiosurgery (SRS)) in the management of metastatic breast cancer (mBC) patients remains unclear. This study aimed to assess the efficacy of SBRT/SRS in oligometastatic and oligoprogressive breast cancer patients.MethodsTotally 80 mBC patients with oligometastatic disease (OMD) and 80 with oligoprogressive disease (OPD) to ≤5 metastatic lesions were retrospectively analyzed. The endpoint was overall survival and progression-free survival, and univariate and multivariate analyses were performed for survival analysis.ResultsTotally 160 mBC cases (80 OMD and 80 OPD cases) were analyzed, with a total of 291 treated metastases. In the study of OMD, we analyzed 30 cases with oligo-recurrence and 50 cases with sync-oligometastases. The median follow-up time was 46 months, and 1-, 2-, and 3-year OS rates for all patients were 89.8%, 77.6%, and 67.3%, respectively, and the 1-, 2-, and 3-year PFS rates were 71.4%, 44.9%, and 34.7% respectively. In multivariate analysis (MVA), treatment for oligometastases and non-triple-negative status predicted favorable OS. In patients with oligometastases, median OS was 58 months, and 1-, 2-, and 3-year OS rates were 100%, 91.7%, and 83.3%, respectively; median OS in patients with oligoprogression was 35 months, and 1-, 2-, and 3-year OS rates were 80%, 64%, and 52%, respectively. In mBC cases with limited brain metastases administered SRS, poor OS was detected in patient age under 45 years (P = 0.041), triple-negative cases (P = 0.025), and those with OPD (P = 0.022). In OMD, a significant improvement in PFS was observed in the oligo-recurrence group compared to the sync-oligometastases group (P = 0.013).ConclusionPatients administered local ablative radiotherapy (SBRT/SRS) for oligometastases have better overall survival than those treated for oligoprogression. SBRT/SRS may be beneficial for young and non-triple-negative mBC cases. The presence of oligo-recurrence can predict a favorable prognosis of oligometastases in patients with mBC treated with SBRT/SRS.

Short-Course Blinatumomab Treatment as a Bridge to Further Salvage Therapy for Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia: A Retrospective Single-Center Study.

The high cost of blinatumomab in full doses of full treatments has led to dose reduction and fewer treatment cycles for most patients in China. With current needs for cost-efficiency and resource management in health care, we retrospectively evaluated the clinical effects of short-course blinatumomab treatment for R/R Ph- B-ALL at our center. Blinatumomab was administered with 24-h continuous intravenous infusion (9 μg/day for the first 3 days and 28 μg/day for 6-10 days). The clinical data of 30 R/R B-ALL patients were collected and analyzed. A total of 25 patients (83.3%) including 13 (43.3%) with a high leukemic load (> 50%) achieved morphological CR. Twelve patients (40%) were MRD-negative. The estimated 2-year OS rate was 82.62%. The 2-year PFS rate was 78.35%. The estimated 2-year OS and PFS were significantly better in patients receiving further treatment. Our findings provide novel insights into the optimization of blinatumomab therapy, proposing a viable treatment alternative that aligns with current needs for cost-efficiency and resource management in health care.

A systematic review of stereotactic radiosurgery for metastatic spinal sarcomas.

Sarcomas metastasizing to the spine are a rare entity. Ideally an En-bloc resection is necessary to achieve durable local control (LC) rates. However, anatomical constraints often limit the degree of tumor resection. Because of this, other therapeutic modalities either replacing or as an adjuvant to resection are necessary. Stereotactic radiosurgery (SRS) is a reasonable candidate therapy. We conducted a systematic review of the literature using the following databases: PubMed, Science Direct, and Cochrane library. We used a combination of the following terms connected by boolean operators: "Metastatic Sarcoma, Sarcoma of the Spine, Spine Sarcoma, Metastasis, stereotactic radiosurgery, SRS." All retrospective and prospective cohorts, as well as randomized control trials reporting on patients with histopathologically confirmed metastatic sarcomas of the bony elements of the vertebrae, thecal sac, cord, or associated soft tissues of the spine were included. We excluded animal studies, case reports, case series, patients < 18 (pediatric cohorts), review articles and meta-analyses. No date filters were applied to our search. Our final analysis included 5 studies ranging from 2009 to 2024 reporting on 260 patients and 371 associated lesions. Leiomyosarcoma was the most frequently reported histologic subtype (60%). Most lesions were localized to the thoracic spine (48.6%). 75% of studies reported a median dose < 30Gy, and achieved biologically equivalent doses (BEDs) ranging from < 50-100. Pooled 1-year median survival was 64.5% (IQR: 61.8-75.10). Pooled 1-year median LC was 86% (IQR: 79.4-88.5). Three of five studies (60%) for OS and 4/5 (80%) for LC had data availability suitable for meta-analysis. The 1-year OS and LC rates proportions across these studies were 67% (proportion = 0.67, 95% CI: 0.57-0.75, p = 0.07, I2 = 63%), and 84% (proportion = 0.84, 95% CI: 0.78-0.89, p = 0.10, I2 = 52%) respectively. Median follow up across all studies was 18 months (IQR:12.7-31.3). SRS is a reasonable alternative therapy in either the up front, salvage or adjuvant setting which can facilitate durable LC.

Subjective global assessment for nutritional screening and its impact on surgical outcomes: A prospective study in older patients with colorectal cancer

PurposeOur perioperative management center provides preoperative intervention and functional and nutritional assessments for colorectal cancer patients aged over 75 years. This study evaluated the associations of preoperative nutritional status with postoperative outcomes and prognosis in colorectal cancer patients aged 75 years or older.MethodsThis was a prospective, observational study of 71 colorectal cancer patients aged 75 years or older who underwent surgery between July 2020 and September 2022. The Subjective Global Assessment (SGA) was evaluated as a nutritional index. The patients were classified into three groups: SGA-A (well nourished), B (moderately malnourished), and C (severely malnourished), and the correlations with postoperative outcomes and prognosis were examined.ResultsThe median age of the 71 patients (34 males, 37 females) was 78 (75–92) years, and their median body mass index (BMI) was 22.3 (13.4–31.9) kg/m2. Forty-eight patients had colon cancer, and 23 had rectal cancer. On the SGA, 28 patients were SGA-A, 25 SGA-B, and 18 SGA-C. The SGA-B/C group had significantly higher BMI (p < 0.01) and more ICU admissions (p = 0.02). The G8 score was significantly lower (p = 0.03) in the SGA-B/C group, suggesting coexisting functional decline. In terms of postoperative outcomes, the SGA-B/C group had a significantly longer postoperative hospital stay (p = 0.04). The 3-year OS rates for all stages were 100% in the SGA-A group and 49.7% in the SGA-B/C group (p = 0.03), while the 3-year OS rates for patients excluding Stage IV were 100% in the SGA-A group and 68.5% in the SGA-B/C group, not significantly different (p = 0.14). The 3-year RFS rate was 95.5% in the SGA-A group and 65.3% in the SGA-B/C group (p = 0.15).ConclusionThe SGA is a promising nutritional index associated with short-term outcomes in older patients undergoing colorectal cancer surgery. The SGA can be assessed in a few minutes during an outpatient visit, making it useful for routine clinical use.

Trajectories of postoperative hepatitis B virus (HBV) DNA and HBV-related hepatocellular carcinoma outcomes

BackgroundPreoperative hepatitis B virus (HBV) DNA level has been shown to correlate with the prognosis of patients with HBV-associated hepatocellular carcinoma (HCC) following liver resection, but its dynamic changes have not been reported. The aim of this longitudinal multicenter retrospective observational study was to describe the trajectory of HBV DNA after R0 liver resection in patients receiving antiviral therapy and to investigate its impact on clinical outcomes. MethodsThis study included patients with HBV-related HCC from nine hospitals in China who received antiviral therapy and R0 hepatectomy between 2015 and 2016. A latent class growth mixed model (LCGMM) was applied to group the trajectories of HBV DNA changes. The relative importance of each variable to predict survival was evaluated using the χ2. ResultsSix hundred and eighty-four patients with HCC who met the inclusion exclusion criteria were included. Patients were divided into 5 trajectories of HBV DNA changes using LCGMM. By combining subgroups with similar survival characteristics, patients were reclassified into three groups: slow decline, slow zeroing, and fast zeroing group, the 5-year OS rates are 34.5%, 53.0%, 70.9%, respectively. Multifactorial COX regression results showed that ALBI grade, HBV reactivation, cirrhosis, maximum tumor diameter, microvascular invasion, and HBV DNA trajectory groups were independent risk factors for OS. ConclusionsHBV DNA trajectories were associated with OS for patients with HBV-related HCC after R0 liver resection, and it is necessary to receive antiviral therapy and to monitor HBV status regularly.

Strategies for Recurrent Colorectal Liver Metastases Based on Prognostic Factors and Resectability: Potential Benefit of Multidisciplinary Treatment.

Colorectal liver metastasis (CLM) is classified into technical and oncologic categories, with recommended treatments for each resectability category. However, the classification of recurrent CLM has not been established to date. This study evaluated patients with CLM who underwent initial liver resection between 2006 and 2020 and subsequently experienced liver recurrence. Long-term outcomes and prognostic factors associated with recurrent CLM were investigated. From 949 patients who underwent an initial liver resection, the analysis included 392 patients with liver recurrence. Repeat liver resection was associated with a significantly longer prognosis than non-resection (5-year overall survival [OS] from initial liver resection: 66.3 % vs 27.2 %, p < 0.0001). Multivariable analysis indicated the following independent prognostic factors: four or more recurrent tumors (p = 0.015), tumor 5 cm or larger in size (p = 0.004), and presence of extrahepatic diseases (p = 0.003). The patients were stratified into resectable, borderline resectable, and unresectable recurrent CLM groups based on these criteria. The prognosis varied significantly across the groups, with 5-year OS rates of 67.3 % for resectable recurrent CLM, 30.8 % for borderline resectable recurrent CLM, and 2.6 % for unresectable recurrent CLM (p < 0.0001). Patients with borderline resectable recurrent CLM who did not receive adjuvant chemotherapy after initial liver resection had a positive prognostic impact of preoperative chemotherapy (p = 0.049). The significant independent predictors of recurrent CLM prognosis were four or more tumors, tumor size of 5 cm or larger, and the presence of extrahepatic diseases at recurrence. It is critical to onsider the current condition and tumor resectability at the time of recurrence, and tailored treatments could further improve recurrent CLM outcomes.

Differences in the epidemiology and survival of patients with colorectal cancer between China and the United States: a large cross-sectional study.

Studying the epidemiological and management characteristics of colorectal cancer (CRC) between China and the US has important implications. The present cross-sectional study included patients from SEER and Southwest China Colorectal (SCC) databases. Incidence, treatment and survival information were compared between two countries.86859 patients in the SEER database and 5838 patients in the SCC database were included. The estimated incidence of CRC in the US was greater than that in China from 2006 to 2019. The most common tumor sites of CRC patients in China were the RSC (66.5%), RCC (20.2%) and LCC (13.3%), while those in the US were the RCC (44.4%), RSC (29.8%) and LCC (25.8%). Chinese CRC patients were more likely to be male (58.9% vs 52.4%, p < 0.001), have a greater stage II CRC rate (49.8% vs 27.8%, p < 0.001), younger age at diagnosis (median 64 vs 66years, p < 0.001). Radical surgery rates were lower in Chinese RCC (92.3% vs 93.9%, p < 0.001) and LCC (88.9% vs 92.0%, p < 0.001) patients. The adjuvant therapy rates were lower in Chinese CRC patients. The 5-year overall survival rates were 71.8% and 78.2% for Chinese and US CRC patients, respectively (p < 0.001).China is undergoing an increasing incidence of CRC. The treatment and mortality of CRC differ in China and US populations. China had a lower adjuvant therapy rate and a lower 5-year OS rate compared with the US.

CTNI-25. TUMOR TREATING FIELDS (TTFIELDS) THERAPY WITH CHEMORADIATION, FOLLOWED BY MAINTENANCE TTFIELDS THERAPY/TEMOZOLOMIDE (TMZ), IN NEWLY DIAGNOSED GLIOBLASTOMA (NDGBM). RESULTS OF PHASE II CLINICAL STUDY

Abstract INTRODUCTION Tumor-Treating Fields (TTFields) are electric fields that exert physical forces to disrupt cancer cell function and tumor progression via a multimodal mechanism of action. Following the phase 3 pivotal EF-14 study, TTFields therapy concomitant with temozolomide (TMZ) maintenance therapy became approved for newly-diagnosed glioblastoma (ndGBM). Pre-clinical data and pilot clinical studies suggests synergistic effect of concomitant TTFields treatment with radiotherapy (RT). OBJECTIVE To assess the efficacy and safety of first line TTFields therapy concomitant with RT/TMZ vs RT/TMZ alone in adult patients with ndGBM. Design: 69 patients with ndGBM and KPS≥70 stratified by MGMT status, extent of resection, and age, were randomized 1:1. The experimental arm received TTFields therapy from the first day of chemoradiation, the control arm started 4 weeks after completion of chemoradiation. Patients continued TTFields therapy until second disease progression or 24months. The primary endpoint was 1-year PFS rate, and secondary endpoints included PFS, OS, and safety. Kaplan-Meier estimates were used to assess whether PFS and OS were improved with first line TTFields therapy/RT/TMZ vs RT/TMZ with delayed TTFields therapy. RESULTS Overall, 46 patients received maintenance chemotherapy and TTFields therapy. Mean age was 62 years (range:27–77). One-year PFS rate was 36% and 19% in the experimental and control arms, respectively (p-value=0.10). Median PFS was 9.9 and 5.6 months (HR 0.53, p-value 0.049). Median OS was 25.9 and 17 months (HR 0.85, p-value=0.6). Two-year OS rates were 52% and 31% (p-value 0.07). Among patients with high TTFields usage (≥75%) 2-year OS rates were 78% and 34% (p=0.01). CONCLUSIONS The addition of concomitant TTFields to standard treatment with temozolomide and RT for patients with ndGBM appears to be another step in improving the outcome of this patients population. This is further investigated in the large-scale TRIDENT study.

The prognostic implications of podoplanin in cancer-associated fibroblasts and PD-L1 expression in high-grade neuroendocrine carcinoma of the lung.

Podoplanin (PDPN) expression in cancer-associated fibroblasts (CAFs) (CAF-PDPN) is considered a poor prognostic factor in nonsmall cell lung cancer, but little is known about its clinical significance in high-grade neuroendocrine carcinoma of the lung (HGNEC). This study examines the association between CAF-PDPN and stromal programmed death-ligand 1 (PD-L1) expression and the prognostic implications of CAF-PDPN and PD-L1 expression status in surgically resected HGNEC patients. Immunohistochemical analyses were performed on 121 resected HGNEC specimens using antibodies against PDPN and PD-L1. Correlations between CAF-PDPN, stromal PD-L1 expression, and clinicopathologic features and their implications for survival were analyzed statistically. There were substantially more large-cell neuroendocrine carcinomas in the stromal PD-L1-positive group and more vascular invasion in the tumoral PD-L1-positive group. PDPN expression in CAF was moderately correlated with stromal PD-L1 expression (ρ = 0.567, p < 0.001). In a survival analysis combining CAF-PDPN and stromal PD-L1 status, the 5-year RFS rates for Group A: CAF-PDPN (+)/stromal PD-L1 (+), Group B: CAF-PDPN (+)/stromal PD-L1 (-), Group C: CAF-PDPN (-)/stromal PD-L1 (+), and Group D: CAF-PDPN (-)/stromal PD-L1 (-) were 62.0%, 46.8%, 17.5%, and 20.2%, respectively, with corresponding 5-year OS rates of 76.6%, 69.2%, 27.0%, and 25.3%. The log-rank test showed statistically significant differences among the groups in RFS (p < 0.001) and OS (p < 0.001). There is a correlation between CAF-PDPN and tumoral/stromal PD-L1 expression, and positive status for either CAF-PDPN or stromal PD-L1 expression could be an independent favorable prognostic factor in surgically resected HGNEC patients.

Radiofrequency Ablation Therapy versus Stereotactic Body Radiation Therapy for Naive Hepatocellular Carcinoma (≤5cm): A Retrospective Multi-Center Study.

Radiofrequency ablation (RFA) is a micro-invasive treatment for early-stage HCC patients. Stereotactic body radiation therapy (SBRT) has also been proven an effective and safe treatment for HCC patients. This multi-center study is to compare the efficacy of computed tomography (CT)-guided RFA and CT-based SBRT in naïve HCC patients with tumor diameters ≤5 cm. This retrospective cohort study included 1001 treatment-naïve HCC patients from three hospitals or medical centers. The patients received RFA (n = 481) or SBRT (n = 520) treatment between December 2011 and May 2019. Furthermore, subgroup analyses of all patients were conducted based on Couinaud's classification of liver segments. After matching, the local control (LC) rates of the SBRT group were better than those of the RFA group (p=0.024*), which mainly referred to the patients whose tumors were located in the S7/S8 (p=0.006*). Among patients with tumors located in S1, nineteen patients (19/21) underwent SBRT. The 1-, 3- and 5-year LC rates were 100%, 87.8% and 87.8% in the SBRT group, and the 1-, 3- and 5-year OS rates were 100%, 69.8% and 69.8%, respectively. Moreover, the OS rates in S5/S6 group in RFA were higher than those in SBRT group. The LC rates were better in the SBRT group than in the RFA group for the patients with lesions localized in S7/S8, and SBRT could also be a therapeutic option for patients with lesions in S1. Moreover, patients with tumors located in S5/S6 were better candidates for RFA treatment than SBRT.

Comparative analysis of testicular and nontesticular choriocarcinoma: a population-based study.

Germ cell tumors (GCTs) are common solid tumors in young men, originating in the testicles or outside the gonads. Choriocarcinoma, a rare and aggressive subtype, primarily affects females but can also occur in males. Treatment options depend on the stage and location of the tumor, with early recognition being crucial for better outcomes. Comparative studies between testicular and nontesticular choriocarcinoma are crucial for understanding distinct features and prognoses. The study utilized SEER*Stat software to extract data and applied statistical methods such as χ 2 analysis and Kaplan-Meier method. Inclusion criteria focused on patients diagnosed with choriocarcinoma between 2000 and 2018, while exclusion criteria eliminated cases without histological confirmation or with other tumors. Among 363 patients, 270 (74.4%) had testicular CC, and 93 (25.6%) had nontesticular CC. Notably, testicular CC was more common in white patients, which could indicate demographic or environmental factors at play. Patients with testicular CC were more likely to undergo surgery, suggesting a significant treatment trend. It is worth exploring whether patient preferences or observed postsurgery improvements contribute to this pattern. Testicular CC had a higher 5-year OS rate of 54% versus 29%, and a higher 5-year CSS rate of 56.3% versus 31.9%, respectively. This study reveals distinct characteristics and treatment responses in testicular and nontesticular choriocarcinoma, emphasizing the need for personalized management based on subtype. Our findings highlight racial disparities in incidence and the efficacy of surgical intervention for both types, while chemotherapy benefits extragonadal cases and radiotherapy's role requires further evaluation.

Intracranial administration of anti-PD-1 and anti-CTLA-4 immune checkpoint-blocking monoclonal antibodies in patients with recurrent high-grade glioma.

Recurrent high-grade glioma (rHGG) lacks effective life-prolonging treatments and the efficacy of systemic PD-1 and CTLA-4 immune checkpoint inhibitors is limited. The multi-cohort Glitipni phase I trial investigates the safety and feasibility of intraoperative intracerebral (iCer) and postoperative intracavitary (iCav) nivolumab (NIVO) ± ipilimumab (IPI) treatment following maximal safe resection (MSR) in rHGG. Patients received 10 mg IV NIVO within 24 h before surgery, followed by MSR, iCer 5 mg IPI and 10 mg NIVO, and Ommaya catheter placement in the resection cavity. Biweekly postoperative iCav administrations of 1-5-10 mg NIVO (cohort 4) or 10 mg NIVO plus 1-5-10 mg IPI (cohort 7) were combined with 10 mg IV NIVO for 11 cycles. 42 rHGG patients underwent MSR with iCer NIVO + IPI. 16 pts were treated in cohort 4 (postoperative iCav NIVO at escalating doses) while 28 patients were treated in cohort 7 (intra and postoperative iCav NIVO and escalating doses of IPI). The most common TRAE was fatigue; no grade 5 AE occurred. Dose-limiting toxicity was grade 3 neutrophilic pleocytosis (4 pts) receiving iCav NIVO plus 5 or 10 mg IPI. PFS and OS did not significantly differ between cohorts (median OS: 42 [95% CI 26-57] vs. 35 [29-40] weeks; 1-year OS rate: 37% vs. 29%). Baseline B7-H3 expression significantly correlated with worse survival. OS compared favorably to a historical pooled cohort (n = 469) of Belgian rHGG pts treated with anti-VEGF therapies (log-rank P = .015). Intraoperative iCer IPI + NIVO with postoperative iCav NIVO ± IPI up to biweekly doses of 1 mg IPI + 10 mg NIVO is feasible and safe, showing encouraging OS in rHGG patients. ClinicalTrials.gov registration: NCT03233152.

Clinical Features and Prognosis of Patients with Diffuse Large B-Cell Lymphoma of the Breast

To explore the clinical characteristics and prognosis of patients with diffuse large B-cell lymphoma (DLBCL) of the breast. The clinical data of 28 DLBCL patients admitted to Shanxi Provincial Cancer Hospital from January 2013 to January 2023 were retrospectively analysed, including 13 cases of primary breast DLBCL (PB-DLBCL) and 15 cases of secondary breast DLBCL (SB-DLBCL), and the data of their clinical manifestations, laboratory tests, pathological examinations, treatment protocols, and follow-up were statistically analyzed. There were significant differences in IPI score, LDH level and β2- microglobulin between PB-DLBCL and SB-DLBCL patients (P < 0.05). Among the 23 patients with breast DLBCL who received regular treatment, 13 patients achieved complete remission (9 patients with PB-DLBCL and 4 patients with SB-DLBCL) after initial treatment. By the end of follow-up, 11 patients relapsed or progressed (5 patients with PB-DLBCL and 6 patients with SB-DLBCL) and 9 patients died (3 patients with PB-DLBCL and 6 patients with SB-DLBCL). The 5-year OS rate was (75.0±15.3)% in PB-DLBCL group and (32.3±17.1)% in SB-DLBCL group. The 5-year PFS rate was （59.1±19.8）% in PB-DLBCL and 0% in SB-DLBCL group. The 5-year OS rate and PFS rate of PB-DLBCL patients were higher than those of SB-DLBCL patients (P < 0.05); the 5-year OS rate of the combined central preventive treatment group was higher than that of the chemotherapy group (P < 0.05). Breast DLBCL is divided into two categories: PB-DLBCL and SB-DLBCL. Compared with SB-DLBCL, PB-DLBCL has the characteristics of lower IPI score, LDH, and β2-microglobulin levels. PB-DLBCL patients have a longer survival period. In addition, the prognosis of patients receiving central preventive treatment is more optimistic.