5-year Progression-free Survival Research Articles

Clinical and Molecular Characteristics and Outcome of Adult Medulloblastoma at a Tertiary Cancer Center.

Background/Objectives: Adult medulloblastoma is a rare entity, with management data extrapolated from pediatric medulloblastoma cases. We aim to report the clinical characteristics, prognostic factors, and treatment outcome of a cohort of adult patients with medulloblastoma. Methods: Fifty-three patients aged ≥ 18 years with medulloblastoma treated at King Hussein Cancer Center between 2007 and 2019 were retrospectively reviewed. Patients' diseases were staged according to modified Chang's staging system. All patients received adjuvant craniospinal irradiation followed by a posterior fossa boost. Baseline disease characteristics, including molecular subgrouping, were tested as prognostic factors of progression-free survival (PFS) and overall survival (OS) by using univariate analysis. Results: Median follow-up was 70 months (range 37.5-104.5 months). Twenty-two tumors were of the SHH-activated subtype. Conversely, WNT-activated and group 4 tumors had three cases each. Only 37.7% of patients died. The mean 3-year, 5-year, and 10-year OS were 85% (75-95%), 74% (62-87%), and 50% (33-75%), respectively. Significant differences in OS were associated with the extent of surgery (p = 0.017), M stage (p = 0.009), and risk status (p < 0.001). Relapses were detected in 28.3% of cases. The 3-year, 5-year, and 10-year PFS were 81% (71-92%), 75% (63-88%), and 66% (52-83%), respectively. Significant differences in PFS were associated with the extent of surgery (p = 0.008) and risk status (p = 0.012). Molecular subgrouping did not correlate with OS or PFS. Conclusions: Our results revealed poor survival of patients with high-risk disease, which may necessitate the intensification of chemotherapy. Molecular subgrouping did not correlate with the outcome in this cohort.

Visceral Obesity and a High Glasgow Prognostic Score Are Key Prognostic Factors for Metastatic Colorectal Cancer Treated with First Line Chemotherapy.

The prognostic significance of a high visceral fat area (VFA) in metastatic colorectal cancer (mCRC) remains unclear. We evaluated the prognostic impact of high-VFA on the long-term outcomes of patients with mCRC who underwent chemotherapy. Ninety patients with metastatic CRC who underwent chemotherapy were included. VFA measurement was performed by pre-treatment computed tomography using image analysis system. Overall survival (OS) and progression-free survival (PFS) rates were analyzed using the Cox proportional hazards model and Kaplan-Meier curves with the log-rank test. High-VFA was identified in 39 patients. The OS (2-year OS rates: 51.6% vs 33.3%, p=0.0023) and PFS rates (2-year PFS rates: 18.0% vs 2.7%, p=0.012) were significantly lower in the high-VFA group than in the low-VFA group. In multivariate analysis, the independent significant predictors of OS were carbohydrate antigen 19-9 (CA19-9) ≥37.0 U/mL (HR: 1.99, 95%CI [1.20-3.31], p=0.007), Glasgow prognostic score (GPS) of 1 or 2 (HR: 2.65, 95%CI [1.53-4.58], p<0.001), and high-VFA (HR: 3.09, 95%CI [1.81-5.25], p<0.001). Similarly, the independent significant predictors of PFS were CA19-9 ≥37.0 U/mL (HR: 2.02, 95%CI [1.21-3.38], p=0.007), GPS of 1 or 2 (HR: 1.87, 95%CI [1.17-2.99], p=0.008), and high-VFA (HR: 2.65, 95% CI [1.61-4.35], p<0.001). We demonstrated that pre-treatment high-VFA and high-GPS were significantly associated with worse OS and PFS rates in patients with mCRC who underwent chemotherapy.

Twelve-year experience of pineal region meningiomas: long-term outcomes of maximal safe resection.

The purpose of this research was to summarize the clinical and prognostic features of pineal region meningiomas, evaluate treatment strategies and long-term prognoses, and improve the management of pineal region meningiomas. We retrospectively studied the data of 37 patients who received surgical resection for pineal region meningiomas at West China Hospital of Sichuan University from 2009 to 2021. Adjuvant gamma knife radiosurgery (GKRS) was conducted according to the extent of resection (EOR). Progression-free survival (PFS), Karnofsky performance status (KPS) scores and recovery of neurological function were adopted to assess a comprehensive management strategy for pineal region meningiomas. The most common symptom was headache associated with intracranial hypertension (75.7%). The occipital transtentorial approach (40.5%) and supracerebellar infratentorial approach (29.7%) were performed in most cases. Gross total resection (GTR) was achieved in 27 patients (73.0%) and the remaining patients were treated with subtotal resection (STR) combined with postoperative GKRS. With a mean follow-up period of 87.0 months, the progression rate was 10.0%, the 5-year PFS rate was 92.9%, and the ΔKPS was 16.3. Multivariate analysis revealed that the STR + GKRS and supracerebellar infratentorial approach were beneficial to the recovery of quality of life of patients. Pineal region meningiomas are sporadic but challenging. It is necessary to select the most appropriate surgical approach, EOR, and hydrocephalus treatment strategy for patients with pineal region meningiomas. Maximal safe resection to protect neurovascular function combined with postoperative GKRS can significantly improve the quality of life of patients.

Treatment Patterns and Clinical Outcomes in Patients with Hodgkin Lymphoma from Saudi Arabia, Türkiye, and South Africa: Subgroup Analysis from the International Multicenter Retrospective B-HOLISTIC Study

B-HOLISTIC was a real-world retrospective study of treatment patterns and clinical outcomes in Hodgkin lymphoma (HL) in regions outside Europe and North America. This subgroup analysis reports findings from Saudi Arabia, Türkiye, and South Africa. Patients aged ≥18 years and diagnosed with stage IIB-IV classical HL receiving frontline chemotherapy (frontline cHL) and/or with relapsed/refractory HL (RRHL) from January 2010 to December 2013 were assessed. The primary endpoint was progression-free survival (PFS) in patients with RRHL. Overall, 694 patients (RRHL: n=178; frontline cHL: n=653) were enrolled. Among patients with RRHL, >80% received first salvage chemotherapy. The most common first salvage regimens were etoposide, methylprednisolone, cytarabine, and cisplatin in Saudi Arabia (78.3%) and dexamethasone, cytarabine, and cisplatin in Türkiye (36.1%) and South Africa (40%). Median PFS (95% confidence interval [CI]) in the RRHL group was 5.1 (3.0-15.9), 19.7 (7.5-not reached), and 5.2 (1.1-10.1) months in Saudi Arabia, Türkiye, and South Africa, respectively. The 5-year PFS and overall survival (95% CI) rates in patients with RRHL were 33.2% (21.6-45.2) and 78.2% (65.9-86.5) in Saudi Arabia, 42.5% (29.5-54.9) and 79.4% (67.2-87.5) in Türkiye, and 13.1% (4.2-27.0) and 53% (35.5-67.8) in South Africa, respectively. This study showed that the clinical outcomes in Türkiye and Saudi Arabia were generally comparable with those of Western countries during the study period, although Saudi Arabia had lower PFS rates. Conversely, the clinical outcomes in South Africa were suboptimal, emphasizing the need for novel therapies and improved progression to stem cell transplantation. These data may serve as a control group for future studies in these countries and inform clinical decision-making.

MRI radiomics and nutritional-inflammatory biomarkers: a powerful combination for predicting progression-free survival in cervical cancer patients undergoing concurrent chemoradiotherapy

ObjectiveThis study aims to develop and validate a predictive model that integrates clinical features, MRI radiomics, and nutritional-inflammatory biomarkers to forecast progression-free survival (PFS) in cervical cancer (CC) patients undergoing concurrent chemoradiotherapy (CCRT). The goal is to identify high-risk patients and guide personalized treatment.MethodsWe performed a retrospective analysis of 188 patients from two centers, divided into training (132) and validation (56) sets. Clinical data, systemic inflammatory markers, and immune-nutritional indices were collected. Radiomic features from three MRI sequences were extracted and selected for predictive value. We developed and evaluated five models incorporating clinical features, nutritional-inflammatory indicators, and radiomics using C-index. The best-performing model was used to create a nomogram, which was validated through ROC curves, calibration plots, and decision curve analysis (DCA).ResultsModel 5, which integrates clinical features, Systemic Immune-Inflammation Index (SII), Prognostic Nutritional Index (PNI), and MRI radiomics, showed the highest performance. It achieved a C-index of 0.833 (95% CI: 0.792–0.874) in the training set and 0.789 (95% CI: 0.679–0.899) in the validation set. The nomogram derived from Model 5 effectively stratified patients into risk groups, with AUCs of 0.833, 0.941, and 0.973 for 1-year, 3-year, and 5-year PFS in the training set, and 0.812, 0.940, and 0.944 in the validation set.ConclusionsThe integrated model combining clinical features, nutritional-inflammatory biomarkers, and radiomics offers a robust tool for predicting PFS in CC patients undergoing CCRT. The nomogram provides precise predictions, supporting its application in personalized patient management.

Zanubrutinib, obinutuzumab, and venetoclax for first-line treatment of mantle cell lymphoma with a TP53 mutation

AbstractTP53-mutant mantle cell lymphoma (MCL) is associated with poor survival outcomes with standard chemoimmunotherapy. Dual Bruton tyrosine kinase and BCL2-inhibition with or without anti-CD20 monoclonal antibody therapy has shown promising activity in TP53-mutant MCL. We conducted a multicenter, phase 2 study of zanubrutinib, obinutuzumab, and venetoclax (BOVen) in untreated patients with MCL with a TP53 mutation. Patients initially received 160 mg zanubrutinib twice daily and obinutuzumab. Obinutuzumab at a dose of 1000 mg was given on cycle 1 day 1, 8, and 15, and on day 1 of cycles 2 to 8. After 2 cycles, venetoclax was added with weekly dose ramp-up to 400 mg daily. After 24 cycles, if patients were in complete remission with undetectable minimal residual disease (MRD) using an immunosequencing assay, treatment was discontinued. The primary end point was met if ≥11 patients were progression free at 2 years. The study included 25 patients with untreated MCL with a TP53 mutation. The best overall response rate was 96% (24/25) and the complete response rate was 88% (22/25). Frequency of undetectable MRD (uMRD) at a sensitivity level of 1 × 10–5 and uMRD at a sensitivity level of 1 × 10–6 at cycle 13 was 95% (18/19) and 84% (16/19), respectively. With a median follow-up period of 28.2 months, the primary end point was met with a 2-year progression-free survival of 72%, and the 2-year disease-specific and overall survival were 91% and 76%, respectively. Common side effects were generally low grade and included diarrhea (64%), neutropenia (32%), and infusion-related reactions (24%). BOVen was well tolerated and met its primary efficacy end point in TP53-mutant MCL. These data support its use and further evaluation of the BOVen regimen in this high-risk population. This trial was registered at www.ClinicalTrials.gov as #NCT03824483.

Implementing the optimized hippo-avoidance prophylactic cranial irradiation for limited-stage small cell lung cancer by tomotherapy and volumetric modulated arc therapy.

Hippo-avoidance prophylactic cranial irradiation (HA-PCI) requires a hippocampal avoidance zone expanded from hippocampus to ensure dose fall-off and compensate for setup errors. Most studies recommend a 5-mm margin, while it could be optimized to a 2-mm expansion. Here, we showed the details of optimized HA-PCI for limited-stage small cell lung cancer (LS-SCLC). This cohort study reviewed patients with LS-SCLC receiving optimized HA-PCI from August 2014 to June 2020 in the National Cancer Center of China. The hippo-related dose parameters were summarized. The comparison of the Hopkins Verbal Learning Test-Revised (HVLT-R) scores in different time points was conducted. The Kaplan-Meier method was used to calculate the survival rates. A total of 112 patients were included. The average doses of hippocampus and hippocampal avoidance zone were 6.80 Gy (IQR: 6.40-7.44) and 7.63 Gy (IQR: 7.14-8.39). No differences were observed in the two radiation techniques (tomotherapy [TOMO] vs. volumetric-modulated arc therapy [VMAT]). The decline of HVLT-R score remained in a low level and not significant in assessable patients (p = 0.095). With a median follow-up of 52 months (95% CI: 47.2-56.7), the 2-year overall survival and progression-free survival were 74.1% and 50.0%, respectively. Two intracranial recurrence lesions (2.3%) located <2 mm from the hippocampus. Optimized HA-PCI could achieve similar dose limitation by TOMO and VMAT techniques with favorable efficacy and minor toxicity.

Lymph node ratio is a prognostic indicator for locally advanced gastric cancer after neoadjuvant immunochemotherapy

ObjectiveThe efficacy of lymph node ratio (LNR) as a prognostic indicator in locally advanced gastric cancer (LAGC) patients underwent radical resection after neoadjuvant immunochemotherapy (NICT) remains to be demonstrated. The objective of the current retrospective study is to investigate the relationship between LNR and survival in patients with LAGC who underwent radical resection after NICT.MethodsA retrospective analysis was performed on 121 cases of LAGC in patients underwent radical resection after NICT between July 2020 and October 2023. The LNR values of the patients were divided into two groups using X-tile software. The first group, designated the low LNR group, comprised patients with LNR values of ≤ 33%. The second group, designated the high LNR group, comprised patients with LNR values of > 33%. The correlation between patient survival rates and a range of clinical and pathological variables was examined.ResultsOverall, 121 patients were enrolled: 108 with low-LNR (LNR ≤ 33%) and 13 with high-LNR (LNR > 33%). A better 2-year overall survival (OS) (88.5% vs. 32.6%; p < 0.001) and progression-free survival (PFS) (80.2% vs. 23.5%; p < 0.001) were observed in patients with low LNR. A similar result was also found in those with non-pathological complete response group (non-pCR), where the 2-year OS was 87.2% vs. 32.6% (p < 0.001), and the 2-year PFS was 77.7% vs. 23.5% (p < 0.001). Compared to the pathologic lymph nodes staging (ypN), LNR exhibited similar prognostic capabilities for OS and PFS. Multivariate analysis indicated that LNR was an independent prognostic factor for both OS (HR 6.258, 95% CI 1.798–21.778; p = 0.004) and PFS (HR 3.431, 95% CI 1.341–8.780; p = 0.010), but not ypN.ConclusionsLNR may serve as a viable indicator for prognostication in LAGC patients treated with NICT.

18Fluorodeoxyglucose positron emission tomography (18F-FDG PET)–derived tumoral and peritumoral radiomic parameters can predict pathological subtype and survival in esophageal carcinoma

The aim of this study is to investigate the importance of the quantitative parameters of the tumoral and peritumoral regions in prediction of pathological subtypes and 1-year survival in patients with esophageal carcinoma. A total of 103 patients with esophageal squamous cell carcinoma (SCC) and adenocarcinoma (AC) and in whom 18fluorodeoxyglucose positron emission tomography/computerized tomography (18F-FDG PET/CT) was performed were included in the study. One-year progression-free survival (PFS) and overall survival times of all patients were noted. Primary tumor and peritumoral area were drawn with manual segmentation on the 18F-FDG PET images. Seventy-three quantitative parameters were extracted from tumoral and peritumoral volumes of interest by using software. The differences of parameters of tumoral and peritumoral regions were determined statistically between pathological subtypes and between 1-year survivors and non-survivors. Diagnostic models were created with the statistically significant parameters. The model that consists of a tumoral and a peritumoral parameter could classify the pathological subtypes in 61% of the patients correctly (area under the curve [AUC]: 0.706, 61.2% accuracy, 53.7% sensitivity, and 75% specificity). The model that was created with 2 tumoral parameters could classify the 1-year survival in 66% of the patients correctly (AUC: 0.695, 66% accuracy, 73.6% sensitivity, and 56.1% specificity). The model consisting of a tumoral and a peritumoral parameter detected 1-year PFS in 66% of the patients accurately (AUC: 0.687, 66% accuracy, 72.4% sensitivity, and 55.6% specificity). The quantitative parameters obtained from tumoral and peritumoral regions can provide information about pathological subtypes and 1-year survival in esophageal carcinoma.

Comparison of CHOP-19 and CHOP-25 for treatment of peripheral nodal B-cell lymphoma in dogs: A European multicenter retrospective cohort study.

Peripheral nodal B-cell lymphomas (PNBCL) represent the most common presentation of lymphomas in dogs. Multiagent CHOP (C = cyclophosphamide, H = hydroxydaunorubicin [Doxorubicin], O = Oncovin, P = prednisolone)-based chemotherapy protocols have been widely accepted as gold standard 1st-line treatment. CHOP-25 and CHOP-19 are most commonly prescribed but have never been directly compared. Our primary aim was to compare outcomes of dogs diagnosed with PNBCL, treated using a 1st-line CHOP-19 or CHOP-25 protocol. A secondary objective was to determine the impact of protocol-related variables on outcomes. Five hundred two dogs from 16 European oncology referral centers. One hundred fifty-five dogs were treated with CHOP-19 and 347 dogs with CHOP-25. Retrospective, multicentric cohort study of dogs diagnosed with PNBCL between 2014 and 2021. The 6-month, 1-year, and median progression-free survival (PFS) were 56.5% (95% confidence interval [CI], 49.2-65.0), 14.1% (95% CI, 9.4-21.0), and 196 days (95% CI, 176-233) with CHOP-19; and 56.4% (95% CI, 51.4-61.9), 17% (95% CI, 13.4-21.6), and 209 days (95% CI, 187-224) with CHOP-25. The 1-year, 2-year and median overall survival (OS) were 36.9% (95% CI, 29.7-46.0), 13.5% (95% CI, 8.6-21.1), and 302 days (95% CI, 249-338) with CHOP-19; and 42.8% (95% CI, 37.7-48.7), 15.4% (95% CI, 11.7-20.4), and 321 days (95% CI, 293-357) with CHOP-25. No significant difference in PFS and OS was found between the 2 protocols. Our study confirmed similar outcomes for dogs with PNBCL treated with 1st-line CHOP-19 or CHOP-25. Both protocols therefore could be used as a standard of care in future trials.

Nivolumab+AVD in Advanced-Stage Classic Hodgkin’s Lymphoma

BackgroundIncorporating brentuximab vedotin into the treatment of advanced-stage classic Hodgkin’s lymphoma improves outcomes in adult and pediatric patients. However, brentuximab vedotin increases the toxic effects of treatment in adults, more than half of pediatric patients who receive the drug undergo consolidative radiation, and relapse remains a challenge. Programmed death 1 blockade is effective in Hodgkin’s lymphoma, including in preliminary studies involving previously untreated patients.MethodsWe conducted a phase 3, multicenter, open-label, randomized trial involving patients at least 12 years of age with stage III or IV newly diagnosed Hodgkin’s lymphoma. Patients were randomly assigned to receive brentuximab vedotin with doxorubicin, vinblastine, and dacarbazine (BV+AVD) or nivolumab with doxorubicin, vinblastine, and dacarbazine (N+AVD). Prespecified patients could receive radiation therapy directed to residual metabolically active lesions. The primary end point was progression-free survival, defined as the time from randomization to the first observation of progressive disease or death from any cause.ResultsOf 994 patients who underwent randomization, 970 were included in the intention-to-treat population for efficacy analyses. At the second planned interim analysis, with a median follow-up of 12.1 months, the threshold for efficacy was crossed, indicating that N+AVD significantly improved progression-free survival as compared with BV+AVD (hazard ratio for disease progression or death, 0.48; 99% confidence interval [CI], 0.27 to 0.87; two-sided P=0.001). Owing to the short follow-up time, we repeated the analysis with longer follow-up; with a median follow-up of 2.1 years (range, 0 to 4.2 years), the 2-year progression-free survival was 92% (95% CI, 89 to 94) with N+AVD, as compared with 83% (95% CI, 79 to 86) with BV+AVD (hazard ratio for disease progression or death, 0.45; 95% CI, 0.30 to 0.65). Overall, 7 patients received radiation therapy. Immune-related adverse events were infrequent with nivolumab; brentuximab vedotin was associated with more treatment discontinuation.ConclusionsN+AVD resulted in longer progression-free survival than BV+AVD in adolescents and adults with stage III or IV advanced-stage classic Hodgkin’s lymphoma and had a better side-effect profile. (Funded by the National Cancer Institute of the National Institutes of Health and others; S1826 ClinicalTrials.gov number, NCT03907488.)

External validation and calibration of the HoLISTIC Consortium's advanced-stage Hodgkin lymphoma international prognostic index (A-HIPI) in the Brazilian Hodgkin lymphoma registry.

The Hodgkin lymphoma International Study for Individual Care (HoLISTIC) Consortium's A-HIPI model, developed in 2022 for advanced-stage classical Hodgkin lymphoma (cHL), predicts survival within 5 years amongst newly diagnosed patients. This study validates its performance in the Brazilian Hodgkin lymphoma registry. By 2022, the Brazilian HL registry included 1357 cHL patients, with a median 5-year follow-up. Probabilities for 5-year progression-free survival (PFS) and overall survival (OS) were calculated using A-HIPI-model equations. Discrimination (Harrell C-statistic/Uno C-statistic) and calibration measures assessed external validation and calibration. Lab values beyond the allowed range were excluded, mirroring the initial A-HIPI analysis. A total of 694 advanced-stage cHL patients met the original inclusion criteria (age 18-65 years, Stage IIB-IV). Median age was 31 years; 46.3% were females. Stage distribution was IIB (33.1%), III (27.4%), IV (39.5%). Bulky disease in 32.6%. Five-year PFS and OS were 68.4% and 86.0%, respectively. Harrell C-statistics were 0.60 for PFS and 0.69 for OS, and Uno C-statistics were 0.63 for PFS and 0.72 for OS. Calibration plots demonstrated well-calibrated predictions with calibration slopes of 0.91 and 1.03 for 5-year OS and PFS, respectively. Despite differing patient, clinical characteristics, and socioeconomic factors, the baseline prediction tool performed well in the Brazilian cohort, demonstrating adequate discrimination and calibration. This supports its reliability in diverse settings.

Dose escalation with stereotactic body radiotherapy for cervical cancer treatment

BackgroundDose escalation with brachytherapy after pelvic irradiation is standard for treating cervical cancer. Its application can be impossible for some patients. Dose escalation with SBRT is widely used with high local control and acceptable toxicity rates in different body parts. The study enrolled patients who underwent SBRT treatment for dose escalation in the cervix.MethodsPatients who were pathologically diagnosed and treated with cervical SBRT after definitive CRT were included in the study. A total of 30 Gy in 5 fractions for the high-risk volume was prescribed. The first response evaluation was performed three months after the completion of treatment. Treatment toxicity was documented according to the RTOG-EORTC scale. Oncological outcomes and toxicity were assessed.ResultsBetween 02.2019 and 05.2023, 40 patients were treated with an SBRT boost after pelvic irradiation. The median follow-up time was 16 months (7–44 months). The median HR CTV was 47 cc (8,3-168,2 cc). There were 39 patients who achieved a complete response and one who achieved a partial response in the third month after treatment. There were two local or two regional recurrences. The 1-year metastasis-free survival was 88%, and the 1-year progression-free survival was 88%. During the follow-up period, one grade 3 gastrointestinal side effect was observed.ConclusionsSBRT which has low toxicity and reasonable locoregional control rates in a short follow-up period, may be an option for dose escalation in brachytherapy-ineligible cervical cancer patients.

Perioperative chemotherapy and nivolumab in non-small-cell lung cancer (NADIM): 5-year clinical outcomes from a multicentre, single-arm, phase 2 trial

Perioperative immunotherapy improves short-term outcomes in resectable non-small-cell lung cancer (NSCLC). We now report 5-year survival from the NADIM trial to assess its long-term benefit. NADIM was a multicentre, single-arm, phase 2 trial conducted across 18 hospitals in Spain. Patients were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status of 0 or 1, and had histologically or cytologically confirmed, treatment-naive, resectable stage IIIA NSCLC (American Joint Committee on Cancer, 7th edition criteria). The neoadjuvant treatment consisted of three cycles of intravenous paclitaxel (200 mg/m2) and carboplatin (area under the curve 6 mg/mL per min) with nivolumab (360 mg). After surgery, 1 year of adjuvant treatment with intravenous nivolumab monotherapy was administered (240 mg every 2 weeks for 4 months, followed by 480 mg every 4 weeks for 8 months). The primary endpoint was 24-month progression-free survival, with 5-year progression-free survival and overall survival as secondary endpoints, assessed in the intention-to-treat population (ie, all patients who received neoadjuvant treatment). Toxicity profile was also assessed as a secondary endpoint. This trial is registered at ClinicalTrials.gov (NCT03081689) and is complete; this is the final report of the trial. Between April 26, 2017, and Aug 25, 2018, 51 patients were assessed for eligibility, of whom 46 comprised the intention-to-treat population (34 [74%] male and 12 [26%] female, median age 63 years [IQR 58-70]). Follow-up was concluded at 60 months (data cutoff July 11, 2023; median follow-up 60·0 months [IQR 60·0-60·0]). 5-year progression-free survival in the intention-to-treat population was 65·0% (95% CI 49·4-76·9), and overall survival was 69·3% (53·7-80·6). Disease progression occurred in 11 (24%) patients; 14 (30%) patients died, including nine (20%) from disease relapse and five (11%) from non-tumour-related causes. Treatment-related adverse events (TRAEs) of grade 3 or worse occurred in 14 (30%) of 46 patients during neoadjuvant treatment and in seven (19%) of 37 during adjuvant treatment. The most common grade 3 or worse TRAEs were increased lipase and febrile neutropenia (three [7%] each) during neoadjuvant treatment, and elevated serum lipase (four [7%]) and elevated serum amylase (three [8%]) during adjuvant treatment. Serious TRAEs included elevated serum lipase and neutropenia (one [2%] each) during neoadjuvant treatment, and elevated serum lipase (one [3%]) during adjuvant treatment. No treatment-related surgery delays, deaths, or unexpected long-term toxicities were reported. Perioperative chemoimmunotherapy showed a promising long-term benefit with no concerning safety data, reinforcing its use in resectable stage IIIA NSCLC. Bristol-Myers Squibb, Spanish Ministry of Science, Instituto de Salud Carlos III, European Union.

Involved-field high-dose chemoradiotherapy with respiratory motion management for esophageal squamous cell carcinoma.

We investigated the clinical outcomes of involved-field high-dose (≥66 Gy) chemoradiotherapy (CRT) combined with respiratory motion management for esophageal squamous cell carcinoma (ESCC). Patients who underwent definitive CRT for histologically confirmed ESCC in our department between 2012 and 2018 were retrospectively analyzed. Respiratory motion management strategies included breath-holding (63%) and mask immobilization (29%) based on individual measurements of respiratory tumor motion using radiographic fluoroscopy with endoscopically placed clip markers as landmarks. We evaluated patient characteristics, treatment efficacy, failure patterns, and toxicities. We enrolled 35 patients with a prescribed dose of 66-70 Gy in 33-35 fractions. The overall response rate within 6 months post-CRT was 94.3%; the median follow-up period for survivors was 43 months. The 2-year overall survival (OS), progression-free survival, and locoregional failure-free survival rates were 51.4%, 42.9%, and 42.9%, respectively. A significant difference in OS was observed between patients with and without esophageal fistulas after CRT (p = 0.002, log-rank test). Disease failure occurred in 16 patients (45.7%), including one (2.9%) with out-of-field regional nodal failure. Major grade 3 or higher toxicities included decreased white blood cell count (48.6%), neutrophil count (34.3%), and esophageal stenosis (31.4%). No grade 3 or higher cardiopulmonary toxicities were observed. Bronchial/tracheal tumor compression and a higher radiotherapy dose (70 Gy) were significantly correlated with esophageal fistulas. Involved-field high-dose CRT with respiratory motion management may be a feasible treatment option for ESCC. However, a comprehensive assessment of esophageal fistula risk is required to identify suitable candidates.

High dose chemotherapy with autologous stem cell rescue in children and young adults with high-risk Ewing sarcoma: A single institute experience in Taiwan.

A combination treatment of surgery, chemotherapy, and radiotherapy can improve the survivals of pediatric patients with Ewing sarcoma (ES). However, prognosis remains poor for patients with metastatic disease at diagnosis or recurrence. Other high-risk (HR) features include large tumor burden, tumors of the axial skeleton and poor histologic response. Several studies have documented high dose chemotherapy with autologous stem cell rescue (HDC-ASCR) to be effective in such patients. In this retrospective study, we present the results of HDC-ASCR for high-risk Ewing sarcoma in children and young adults in a single institute. From March 2004 to March 2021, patients with ES, Ewing-like sarcoma, or round cell sarcoma received HDC-ASCR as part of treatment were included. The patients' characteristics, disease status, stem cell dose, engraftment status, post-transplant complications, and outcomes were analyzed. Twenty patients receiving HDC-ASCR at complete response (n = 6), partial response (n = 13), and stable disease (n = 1) were enrolled. The male to female ratio was 11:9. Median age at diagnosis and transplant was 15.6 years old (range: 3.3-28.9) and 16.2 (range: 4.2-29.9), respectively. The conditioning regimens included ifosfamide-based in two and melphalan-based in 19. All patients achieved successful engraftment without tansplant-related mortality. The 5-year progression-free and overall survival (OS) rate were 35% and 54.5%, respectively. The causes of death (n = 8) were all contributed to disease progression. Patients in the complete response group or with localized HRES exhibited a higher 5-year OS (p = 0.047 and 0.05, respectively). Compared to the historical cohort without HDC-ASCR as part of primary treatment, the current cohort had a significantly better 5-year OS (p = 0.018). HDC-ASCR seems promising as an alternative treatment for HRES in improving OS in this retrospective study with limited case number.

Efficacy of radiotherapy combined with hepatic arterial infusion chemotherapy, TKI and ICI for hepatocellular carcinoma with portal vein tumor thrombus: a retrospective cohort study.

This retrospective study was conducted to evaluate the effectiveness and safety of a new combination therapy of radiotherapy (RT), hepatic arterial infusion chemotherapy (HAIC), tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICI) for hepatocellular carcinoma (HCC) patients involving portal vein tumor thrombus (PVTT). A total of 71 HCC patients with PVTT were retrospectively analyzed: 45 patients were treated by 'HAIC + TKI + ICI' therapy and 26 patients by the new combination therapy. The primary outcomes were overall survival (OS), progression-free survival (PFS), and cumulative survival rate. The PFS in the 'New combination therapy' group was longer than that in the 'HAIC + TKI + ICI' group (HR 0.459, 95%CI 0.253-0.832; P = 0.008). Meanwhile, the OS in the 'New combination therapy' group was also longer than that in the 'HAIC + TKI + ICI' group (HR 0.420, 95%CI 0.198-0.894; P = 0.024). Compared with 'HAIC + TKI + ICI' group patients, the 'New combination therapy' group patients had higher 1-year PFS rate and 1-year OS rate (P = 0.029; P = 0.015). There was no significant difference in the incidence of adverse events between the two groups. The new combination therapy was an effective and safe non-surgical treatment for HCC patients with PVTT and could be considered a preferred therapy option.

Li-Fraumeni-associated osteosarcomas: The French experience.

Describe clinical characteristics and outcome of Li-Fraumeni syndrome (LFS)-associated osteosarcomas. TP53 germline pathogenic/likely pathogenic variant carriers diagnosed with osteosarcoma in France between 1980 and 2019 were identified via the French Li-Fraumeni database at Rouen University Hospital. Sixty-five osteosarcomas in 52 patients with available clinical and histological data were included. The main clinical characteristics were compared with data from National Cancer Institute's SEER (Surveillance, Epidemiology, and End Results) for patients of the same age group. Median age at first osteosarcoma diagnosis was 13.7years (range: 5.9-36.7). Compared to unselected osteosarcomas, LFS-associated osteosarcomas occurred more frequently in patients less than 10years of age (23% vs. 9%), and when compared with osteosarcomas in patients less than 25years were characterized by an excess of axial (16% vs. 10%) and jaw sites (15% vs. 3%) and histology with predominant chondroblastic component and periosteal subtypes (17% vs. 1%). Metastases incidence (25%) was as expected in osteosarcomas. After the first osteosarcoma treatment, the rate of good histologic response (62%) and the 5-year progression-free survival (55%, 95% confidence interval [CI]: 42.6-71.1) were as expected in unselected series of osteosarcomas, whereas the 5-year event-free survival was 36.5% [95% CI: 25.3-52.7] due to the high incidence of second malignancies reaching a 10-year cumulative risk of 43.4% [95% CI: 28.5-57.5]. In osteosarcoma, young age at diagnosis, axial and jaw sites, histology with periosteal or chondroblastic subtype, and synchronous multifocal tumors should prompt suspicion of a germline TP53 mutation. Standard treatments are effective, but multiple malignancies impair prognosis. Early recognition of these patients is crucial for tailored therapy and follow-up.

Clinical outcomes of patients undergoing reoperation with solitary fibrous tumors/hemangiopericytomas and malignant progression of tumors.

The purpose of this study was to analyze the clinical outcomes and malignant progression of tumors in patients who underwent reoperation for recurrent solitary fibrous tumors (SFTs) and hemangiopericytomas (HPCs). We identified 48 patients who underwent reoperation because of tumor recurrence at Tangdu Hospital between January 2010 and December 2021 and analyzed the clinical outcomes, namely, the rate of gross total resection (GTR), progression-free survival (PFS), overall survival (OS), malignant progression of tumors and radiotherapy. The survival curves for each group were plotted using the Kaplan‒Meier method and compared using log-rank tests. Of the 48 patients (25 men and 23 women, mean age 49.5 ± 14.3 years), 25 experienced a second recurrence or metastasis, 15 of whom underwent a third surgery, and the remaining 10 patients who did not undergo surgery ultimately died after tumor progression. The median time (95% CI) to tumor recurrence was 40.0 (32.3-47.7) months after reoperation, with 3-, 5- and 10-year PFS rates of 54.6%, 29.5% and 14.8%, respectively. The median (95% CI) survival time was 70.0 (46.6-93.4) months, with 3-, 5- and 10-year survival rates of 67.9%, 55.1% and 36.7%, respectively. Among the 48 patients who underwent reoperation, 27 (56.3%) achieved GTR, and 21 (43.8%) achieved STR. Twelve patients in the GTR group (12/27, 44.4%) received radiotherapy after surgery, and 18 patients in the STR group (18/21, 85.7%) received radiotherapy. Of the 48 recurrent SFTs, 24 were classified as WHO grade 1, 14 were classified as WHO grade 2, and 10 were classified as WHO grade 3 based on 2021 WHO classification after the primary operation. After reoperation, 9 tumors developed malignant progression, including 4 WHO grade 1 tumors progressing to WHO grade 2 tumors, 1 WHO grade 1 tumor progressing to a WHO grade 3 tumor and 4 WHO grade 2 tumors progressing to WHO grade 3 tumors. GTR after reoperation was associated with better PFS and OS compared to STR. However, the PFS after the third surgery was significantly shorter than that after the second surgery, and the rate of GTR also decreased. Malignant progression may occur after second or third tumor recurrence. Furthermore, compared with WHO grade 1 SFTs, WHO grade 2 and grade 3 SFTs significantly decreased PFS, but OS did not differ among the three groups. Radiotherapy did not prolong PFS or OS in patients who underwent reoperation.

Impact of systemic steroids on the efficacy of first line imatinib treatment of patients with advanced gastrointestinal stromal tumors (GISTs).

Effective management of adverse events is required to maintain sufficient imatinib dosing when treating patients with gastrointestinal stromal tumors (GISTs). Skin rash is a common adverse event of imatinib, which can be effectively controlled by systemic steroid treatment without imatinib dose modification or interruption. However, the impact of the use of systemic steroids on the efficacy of imatinib treatment remains unclear. Between October 2014 and February 2022, 277 consecutive patients from a prospective registry of GIST patients were included as the study population. Patients who started systemic steroids due to grade ≥ 3 skin rash or grade 2 skin rash with grade 2 pruritis were classified as the steroid group, whereas patients who did not develop a skin rash or those who did not require steroids for a mild skin rash were classified as the control group. Efficacy outcomes were compared between the two groups. Among the 277 patients, 30 (10.8%) were treated with systemic steroids for skin rash. There was no significant difference in progression free survival (PFS) or overall survival (OS) between the steroid and control groups (3-year PFS, 67.7% vs. 65.1%, p = 0.53; 3-year OS, 91% vs. 89.9%, p = 0.67, respectively). The use of systemic steroids was not an independent factor associated with PFS (hazard ratio 0.73, 95% confidence interval 0.36-1.49, p = 0.39) and OS (hazard ratio 0.37, 95% confidence interval 0.12-1.18, p = 0.09). In the steroid group, patients who successfully maintained the imatinib dosage showed a trend toward more favorable survival outcomes than those who did not (3-year PFS, 73.3% vs. 44.4%, p = 0.34; 3-year OS, 95.8% vs. 75.0%, p = 0.15, respectively). The use of systemic steroids for the control of imatinib induced severe skin rash did not adversely affect the efficacy outcomes of imatinib in patients with advanced GIST.