Significant Prognostic Factor For Progression-free Survival Research Articles

Efficacy of durvalumab plus tremelimumab treatment for unresectable hepatocellular carcinoma in immunotherapy era clinical practice.

Since the development of tremelimumab plus durvalumab (Dur/Tre) for unresectable hepatocellular carcinoma (uHCC), it has been used as not only an initial but also later line treatment in clinical practice. This study aimed to elucidate clinical prognostic factors for progression-free survival (PFS) in Dur/Tre treatment cases. Enrolled were 183 uHCC patients treated with Dur/Tre from 2023 to May 2024 (median age, 74years; male patients, 152; Child-Pugh class A:B, 150:33; Barcelona Clinic Liver Cancer stage B:C,59:124; initial line use, 64). Clinical factors with prognostic influence on PFS in these patients were retrospectively evaluated. The median observation period was 7.2months (interquartile range, 3.2-10.4). History of atezolizumab plus bevacizumab (Atz/Bev) treatment was the only significant prognostic factor for PFS at introduction of Dur/Tre in multivariate analysis (hazard ratio 2.040, p=0.028) (median PFS: without vs. with=5.6 vs. 2.7months, p<0.001). Although immune-mediated adverse events (imAE) occurrence was only significant in univariate analysis, when objective response and disease control rates were examined according to imAE positivity (any grade) at the time of analysis, those were noted in 14.4% and 39.2%, respectively, of patients without imAE, while in patients with imAE (any grade), they were noted in 18.2% and 56.1%, respectively (p=0.523 and p=0.038, respectively). History of Atz/Bev treatment may be an independent clinical factor for poor PFS at Dur/Tre introduction.

Prognostic significance of diffuse increased fluorine-18-fluorodeoxyglucose (18F-FDG) uptake within the reticuloendothelial system in lymphoma patients.

As constituents of the reticuloendothelial system, the spleen and bone marrow (BM) have been recognized as integral components of the systemic inflammatory response in cancer contexts, thereby serving as predictive indicators for assessing cancer prognosis. Fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) has attained widespread utilization for staging, assessing treatment response, and prognostication in lymphoma patients. Several investigations have proposed that focal increased 18F-FDG uptake in the BM or spleen may correlate with malignant involvement in lymphoma. However, scant data exist regarding the implications of diffuse BM and splenic uptake. This study aimed to explore the relationships between metabolic parameters of the spleen and BM on 18F-FDG PET/CT and inflammatory markers, and to assess their prognostic value in patients with lymphoma. A retrospective analysis was conducted on 118 patients newly diagnosed with malignant lymphoma, who underwent 18F-FDG PET/CT and exhibited diffuse increased splenic or BM uptake in 18F-FDG PET/CT imaging. The mean standardized uptake value (SUV) of the spleen, BM, and liver was calculated. The association between metabolic variables and systemic inflammatory markers was investigated, and the prognostic significance of clinicopathological and PET parameters was assessed using overall survival (OS) and progression-free survival (PFS). A statistically significant correlation was found between the spleen-to-liver SUV ratio (SLR) and inflammatory markers such as C-reactive protein (r=0.264, P=0.007) and platelet-to-lymphocyte ratio (r=0.227, P=0.021). No significant correlation was observed between BM-to-liver SUV ratio (BLR) and hematologic parameters, while concordance analysis revealed a fair agreement between BLR and bone marrow biopsy (BMB) (Cohen's Kappa-κ =0.271, P=0.002). In patients with aggressive non-Hodgkin lymphoma, both SLR [P=0.017, HR 2.715, 95% confidence interval (CI): 0.875-8.428] and BLR (P=0.044, HR 0.795, 95% CI: 0.348-1.813) were significantly linked to OS, while SLR (P=0.019, HR 2.223, 95% CI: 1.139-4.342) emerged as a significant prognostic factor for PFS. This study highlighted that diffuse increased splenic 18F-FDG uptake in lymphoma patients was closely associated with inflammation, whereas diffuse BM uptake was likely attributable to BM infiltration rather than inflammatory changes. Furthermore, both parameters held promise as prognostic indicators for patients with aggressive lymphoma.

Prognostic Role of Clinicopathological Characteristics and Serum Markers in Metastatic Melanoma Patients Treated with BRAF and MEK Inhibitors.

A total of 199 patients with advanced melanoma treated with BRAF + MEK inhibitors were included in our single-center retrospective study. We analyzed the risk of progression and death using multivariate Cox proportional hazard models. The predictive effect of prognostic factors on progression-free survival (PFS) was evaluated in ROC analysis. We found that primary tumor localization, Clark level, pT category, baseline M stage and baseline serum S100B are independent and significant prognostic factors for PFS. The discriminative power of the combination of these factors was excellent for predicting 18 month PFS (AUC 0.822 [95% CI 0.727; 0.916], p < 0.001). Primary tumor localization on the extremities, Clark level V, baseline M1c stage or M1d stage, and elevated baseline serum S100B and LDH levels were independently and significantly associated with unfavorable overall survival (OS). Baseline M stage and serum S100B appear to be independent prognostic factors for both PFS and OS in melanoma patients treated with BRAF + MEK inhibitors. We newly identified significant and independent prognostic effects of primary tumor localization and Clark level on survival that warrant further investigation.

Survival Analysis of Patients Undergoing Intraoperative Contrast-enhanced Ultrasound in the Surgical Treatment of Malignant Glioma.

Complete resection of malignant gliomas is often challenging. Our previous study indicated that intraoperative contrast-enhanced ultrasound (ICEUS) could aid in the detection of residual tumor remnants and the total removal of brain lesions. This study aimed to investigate the survival rates of patients undergoing resection with or without the use of ICEUS and to assess the impact of ICEUS on the prognosis of patients with malignant glioma. A total of 64 patients diagnosed with malignant glioma (WHO grade HI and IV) who underwent surgery between 2012 and 2018 were included. Among them, 29 patients received ICEUS. The effects of ICEUS on overall survival (OS) and progression-free survival (PFS) of patients were evaluated. A quantitative analysis was performed to compare ICEUS parameters between gliomas and the surrounding tissues. The ICEUS group showed better survival rates both in OS and PFS than the control group. The univariate analysis revealed that age, pathology and ICEUS were significant prognostic factors for PFS, with only age being a significant prognostic factor for OS. In multivariate analysis, age and ICEUS were significant prognostic factors for both OS and PFS. The quantitative analysis showed that the intensity and transit time of microbubbles reaching the tumors were significantly different from those of microbubbles reaching the surrounding tissue. ICEUS facilitates the identification of residual tumors. Age and ICEUS are prognostic factors for malignant glioma surgery, and use of ICEUS offers a better prognosis for patients with malignant glioma.

MRI-based volumetric tumor parameters before and during chemoradiation predict tumor recurrence and patient survival in locally advanced cervical cancer: a subgroup analysis of a phase II prospective trial.

This subgroup analysis of a prospective phase II trial aimed to identify valuable and accessible prognostic factors for overall survival (OS) and progression-free survival (PFS) of patients with locally advanced cervical cancer (LACC). Patients with FIGO II to IVA cervical cancer were assessed in this study. All patients underwent concurrent chemoradiotherapy (CCRT) followed by brachytherapy. Tumor parameters based on MRI scans before and during CCRT were evaluated for Overall survival (OS) and Progression-free survival (PFS). A total of 86 patients were included in this analysis with a median follow-up period of 31.7months. Three-year OS and PFS rates for all patients were 87.1% and 76.5%, respectively. Univariate Cox regression analysis showed that restaging tumor size (rTS) over 2.55cm (p < 0.001), initial tumor volume (iTV) over 55.99cc (p < 0.001), downstaging (p = 0.042), and restaging tumor volume (rTV) over 6.25cc (p = 0.006) were significantly associated with OS. rTS (p < 0.001), iTV (p < 0.001), downstaging (p = 0.027), and rTV (p < 0.001) were identified as significant prognostic factors for PFS. In the stepwise multivariable analysis, only rTS > 2.55cm showed statistically significant with OS (HR: 5.47, 95% CI 1.80-9.58, p = 0.035) and PFS (HR: 3.83, 95% CI 1.50-11.45; p = 0.025). Initial tumor size and restaging tumor volume that are easily accessible during radiotherapy provide valuable prognostic information for cervical cancer. MRI-based measurable volumetric scoring system can be readily applied in real-world practice of cervical cancer. This study is a subgroup analysis of prospective trial registered at ClinicalTrials.gov Identifier: NCT02993653.

Radiation Therapy Plays an Important Role in the Treatment of Atypical Teratoid/Rhabdoid Tumors: Analysis of the EU-RHAB Cohorts and Their Precursors

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare malignancy of the central nervous system in young children with a dismal prognosis. Prognostic markers have been extensively investigated but have not been validated. The role of radiation therapy (RT) remains controversial. We evaluated the impact of RT as part of multimodality treatment by analyzing data of a European AT/RT cohort. We retrospectively analyzed data of the European Registry for Rhabdoid Tumors and its precursors. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Potential impact of prognostic factors was analyzed using univariable and multivariable Cox regression analyses with RT as a time-dependent factor. Data of 186 children (118 male, 68 female) treated from 1990 to 2016 were evaluable. The median age at diagnosis was 1.57 years (range, 0.01-26.70 years); 47% (87/186) of the patients were under the age of 18 months. Sixty-nine percent (128/186) received RT (focal RT, n = 93; craniospinal treatment with local boost, n = 34; spinal irradiation, n = 1). The median follow-up duration of the entire cohort was 1.73 years (range, 0.06-20.11 years). The estimated PFS and OS rates were 48% (95% CI, 41%-55%) and 72% (95% CI, 65%-78%) at 1 year and 33% (95% CI, 26%-40%) and 49% (95% CI, 41%-56%) at 2 years, respectively. On multivariable analysis, RT was an independent significant prognostic factor for PFS (hazard ratio, 0.45; 95% CI, 0.27-0.75; P = .002) and OS (hazard ratio, 0.54; 95% CI, 0.32-0.93; P = .025). This analysis confirms the relevance of local therapies. RT was an independent prognostic factor for outcomes in children experiencing AT/RT. However, long-term sequelae have to be carefully evaluated and considered given the young age at time of RT.

Prognostic Value of Baseline Tumor Burden and Tumor Dissemination Extracted From 18 F-FDG PET/CT in a Cohort of Adult Patients With Early or Advanced Hodgkin Lymphoma.

We aimed to assess the prognostic value of baseline tumor burden and dissemination parameters extracted from 18 F-FDG PET/CT in patients with early or advanced Hodgkin lymphoma (HL) treated with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) or escalated BEACOPP (increased bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone). Patients aged ≥18 years with classical Hodgkin lymphoma were retrospectively included. Progression-free survival (PFS) analysis of dichotomized clinicobiological and PET/CT parameters (SUV max , TMTV, TLG, D max , and D bulk ) was performed. Optimal cutoff values for quantitative metrics were defined as the values maximizing the Youden index from receiver operating characteristic analysis. PFS rates were estimated with Kaplan-Meier curves, and the log-rank test was used to assess statistical significance. Hazard ratios were calculated using Cox proportional hazards models. With a median age of 32 years, 166 patients were enrolled. A total of 111 patients had ABVD or ABVD-like treatment with or without radiotherapy and 55 patients with escalated BEACOPP treatment. The median follow-up was 55 months. Only International Prognostic Score (IPS >1), TMTV >107 cm 3 , and TLG >1628 were found to be significant prognostic factors for PFS on univariate analysis. Multivariate analysis revealed that IPS and TLG were independently prognostic and, combined, identified 4 risk groups ( P < 0.001): low (low TLG and low IPS; 4-year PFS, 95%), intermediate-low (high IPS and low TLG; 4-year PFS, 79%), intermediate-high (low IPS and high TLG; 4-year PFS, 78%), and high (high TLG and high IPS; 4-year PFS, 71%). Combining baseline TLG with IPS could improve PFS prediction.

Efficacy and safety of axitinib for metastatic renal cell carcinoma: Real-world data on patients with renal impairment

ObjectivesLimited information is currently available on the efficacy and safety of axitinib for metastatic renal cell carcinoma (mRCC) patients with renal impairment. Therefore, the present study investigated the efficacy and toxicity of axitinib in patients with chronic kidney disease. MethodsPost-hoc analyses were performed on a Japanese multicenter cohort study of 477 mRCC patients who received axitinib followed by 1 or 2 regimens of systemic antiangiogenic therapy between January 2012 and December 2016. Differences in clinical characteristics and the efficacy and safety of axitinib were assessed based on pretreatment renal function. ResultsPatients were categorized into the following 5 renal function groups according to baseline renal function: estimated glomerular filtration rate (eGFR) ≥60 ml/min (n = 133), 45 ml/min ≤eGFR <60 ml/min (n = 153), 30 ml/min ≤eGFR< 45 ml/min (n = 130), eGFR <30 ml/min (n = 45), and dialysis (n = 16). Median progression-free survival (PFS) (95% confidence interval [CI]) in the 5 groups was 11 (8−16), 14 (11−19), 14 (10–19), 12 (8−24), and 6 (3-NR) months, respectively (p = 0.781). After adjustments for treatment-related confounders, the renal function group was not a significant prognostic factor for PFS. Objective response rates in the 5 groups were 22%, 23%, 23%, 18%, 20%, and 38%, respectively (p = 0.468). Regarding adverse events of all grades, hypertension (p = 0.0006) and renal and urinary disorders (p < 0.0001) were more frequently observed in the eGFR <30 ml/min group than in the other groups. ConclusionsSince renal function at the initiation of treatment with axitinib does not adversely affect the efficacy of VEGF-TKI therapy, clinicians do not need to avoid its administration to mRCC patients with impaired renal function in consideration of the risk of progression to end-stage renal disease.

Real-world outcomes of diffuse large B-cell lymphoma in the biosimilar era.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive and the most common type of non-Hodgkin lymphoma (NHL). The clinical use of rituximab has improved the treatment response and survival of patients with DLBCL. The introduction of rituximab biosimilar into healthcare system has helped in providing a cost-effective treatment to B-cell lymphoid malignancies as standard of care and has improved access to patients worldwide. The aim of this study was to observe the real-world effectiveness and safety of Reditux™ and Ristova® in DLBCL patients. Observational study in adults with DLBCL receiving Reditux™ or Ristova® across 29 centers in India (2015-2022). Effectiveness and safety were assessed up to 2 years after first dose. Out of 1,365 patients considered for analysis, 1,250 (91.6%) were treated with Reditux™ and 115 (8.42%) with Ristova®. At 2 years, progression-free survival (PFS) 69% [hazard ratio (HR), 1.16; 95% CI, 0.80-1.67], overall survival (OS) 78.7% (HR, 1.20; 95% CI, 0.78-1.86), response rates, quality of life (QoL), and overall safety in both the cohorts were comparable. The best overall response rate (BORR) at 6 months was comparable with no statistically significant differences between the Reditux™ and the Ristova® cohorts (89.2% vs. 94.3%). In multivariate analysis, BCL-2 and VAS were significant prognostic factors for PFS. Reditux™ and Ristova® were comparable in real-world setting. ISRCTN registry, identifier (ISRCTN13301166).

Long-Term Outcomes in a Phase II Study of Hypofractionated IGRT 60Gy/ 20F in Patients with Isolated Lymph Node Recurrence after Surgery for Esophageal Carcinoma

In oligo metastases in lymph node recurrence after surgery for esophageal cancer, since SBRT (BED>100 Gy10) to mediastinal and abdominal lymph node lesions was not an option due to toxicities in the organs at risk (OAR) such as vessels and gastrointestinal tract, we performed a prospective cohort study of hypofractionated IGRT for isolated lesions. The primary end-points of this study are disease specific survival (DSS) and late treatment toxicities. From 2011 to 2021, 60 Gy/20F/4-4.5wks (78 Gy10) hypofractionated IGRT was performed in a total ITT population of 70 patients after radical surgery (67 cases) and ESD (3 cases), who were diagnosed by CT/PET-CT as having solitary lymph node recurrence (62 cases) or up to 2 adjacent nodes (8 cases). The mean time from surgery to recurrence was 17.9 months (SD 18.1) with a mean age of 67.5 years (SD 9.3), and male to female ratio was 62:8. Pathological results showed that 63 patients (90%) had squamous cell carcinoma. The mean maximum diameter of lesions was 2.5 cm (SD; 1.1 cm). And 51 cases (73%) were treated with CRT concurrently using 5FU plus CDDP (FP), and the rest were treated with RT alone. Lymph node location was lower neck or upper mediastinum in 42 cases, middle and lower mediastinum in 16 cases, and abdomen in 12 cases, respectively. Treatment planning was performed by taking 4DCT fusing PET or MRI images. The Kaplan-Meier method and the Cox proportional hazards regression model were used for overall survival (OS), DSS, and progression free survival (PFS). The mean observation period was 38 months. Primary efficacy was CR in 45 cases (64%), but CR was maintained only in 29 cases (41%). Twenty-two of the 70 patients were relapse-free. OS were 53% and 34% at 2 and 5 years, DSS were 56% and 38% at 2 and 5 years, and PFS were 40% and 39% at 2 and 5 years, respectively. The site of first recurrence was the same or adjacent lymph nodes in 33 cases (47%) and distant metastases in 9 cases (13%). Number of tumors (1 vs. 2), age, and CRT were not significant prognostic factors for OS, DSS, or PFS. In a multivariate analysis, the time from surgery to recurrence ≥12 months was the only significant prognostic factor for PFS (p = 0.018, HR0.50). The same multivariate analysis showed that the only significant prognostic factor for DSS was the location of the recurrent lymph node in the neck and upper mediastinal regions (p = 0.009, HR 0.59). The only late adverse events of Grade 2 or higher were Grade 2 pleural effusion (little and transient) in 6 cases and Grade 2 radiation pneumonitis in 1 case. No acute adverse events were observed other than hematologic toxicity due to FP administration. In locally advanced esophageal cancer, a relatively reliable regional lymph node dissection is often performed, so there is still a chance to aim for cure in cases of solitary recurrence. We found that if the lesion is solitary, localized RT of about 60 Gy/20F/4-4.5 weeks with IGRT can achieve a long-term survival in 40% of patients without any significant adverse events.

The Role of Radiation Therapy for Metastatic Cervical Cancer

Survival rates for women with metastatic cervical cancer (CC) are low, with limited management options. Radiation therapy (RT) for metastatic disease has led to prolonged survival in other malignancies, however, the data are scarce in CC. Herein, we evaluated the effect of RT for metastatic CC. A total of 58 patients with metastatic CC between September 2019 and January 2023 were retrospectively analyzed. All the patients were treated with platinum-based chemotherapy combined with targeted therapy or immunotherapy followed with or without RT (NRT). The recent efficacy, survival status and prognostic factors were analyzed statistically. Objective response rate (ORR) was 63.6% with one complete and twenty partial responses in RT group (n = 33) and 40.0% with two complete and eight partial responses in NRT group (n = 25), respectively (p = 0.074). Disease control rate (DCR) of the RT and NRT groups were 79.4% vs 80.0%, respectively (p = 0.861). Median follow-up time was 17 months (3-39months). In RT group, 11(33.3%) patients experienced local regional or distant failure and 9 (27.3%) patients were dead. In NRT group, 15(60%) patients had progression and 8 (32%) patients dead. There was no significant difference between the two groups in overall survival (OS); however, RT group displayed superior progression-free survival (PFS) (1-year OS: 72.7% vs. 68.0%, p = 0.460; 1-year PFS: 66.7% vs. 40.0%, p = 0.039). The multivariate analysis showed that RT, immunotherapy, lymph node metastasis only relevant predictor of superior PFS but not OS. In subgroup analysis, patients treated with RT appeared to have a better PFS in some specific cohorts, such as age>45 years (72.0% vs 36.4% P = 0.015), squamous carcinoma histology (71.0% vs 40.9% P = 0.017), metastatic at diagnosis (75.0% vs 47.6% P = 0.012), non-targeted therapy (72.4% vs 43.8% P = 0.040). No significant increase in treatment-related toxicity was observed in the RT group compared with the NRT group. RT provided superior PFS in metastatic CC patients compared to NRT, and well tolerated. Moreover, RT, immunotherapy, lymph node metastasis only were independent significant prognostic factors for PFS. Subgroup analysis showed that combination of RT and chemotherapy obtained favorable PFS in metastatic CC patients with age>45 years, squamous carcinoma histology, metastatic at diagnosis, non-targeted therapy. Studies with a larger sample size and longer follow-up are warranted.

High Preoperative Serum D-dimer Predicts Unfavorable Survival Outcomes for Pancreatic Cancer Patients.

Pancreatic cancer cells release certain tissue factors into the bloodstream. It is well known that pancreatic cancer progresses with thrombus formation. Because we routinely measure serum D-dimer levels in preoperative patients as a screening marker of deep venous thrombosis, we examined its association with high serum D-dimer in our cohort of pancreatic cancer resected cases. We examined 315 patients with pancreatic ductal adenocarcinoma who underwent surgical resection in our department from January 2012 to July 2021. All cases were divided into high D-dimer cases (n=118) and low D-dimer cases (n=197) using the cut-off value of 1.0 μg/ml, an institutional upper limit. Clinicohistological characteristics and postoperative survival outcomes were evaluated. Preoperative high D-dimer cases showed significantly worse progression-free survival (PFS) (p=0.021) and overall survival (OS) (p=0.027) than low D-dimer cases; median PFS was 13.9 months versus 21.4 months, and that of OS was 33.4 months versus 68.0 months. Clinicohistological characteristics of high D-dimer cases were age over 70 years (p<0.001), pathological portal vein invasion (p=0.003), and initially borderline resectable or unresectable cases (p=0.027). Multivariate analysis indicated that preoperative high D-dimer was a significant prognostic factor of PFS (hazard ratio=1.42, p=0.025) and OS (hazard ratio=1.51, p=0.036). Preoperative high serum D-dimer over 1.0 μg/ml was associated with pathological portal vein invasion and could be an unfavorable prognostic marker of PFS and OS after surgery, typically due to distant metastasis.

Association Between Lymphopenia and Survival Outcomes in Esophageal Carcinoma Patients Receiving Combined Immunotherapy and Chemoradiotherapy.

To investigate the association between absolute lymphocyte count (ALC) nadir and survival outcomes in esophageal squamous cell carcinoma (ESCC) patients who received definitive chemoradiotherapy (CRT) combined with anti-PD-1 immunotherapy, as well as to explore clinical characteristics and dosimetric parameters that affect ALC nadir during CRT. Patients with ESCC (n = 602) who underwent definitive CRT were analyzed, of whom 166 received combined anti-PD-1 immunotherapy and CRT. Changes in ALC and survival were compared between patients with and without immunotherapy. Propensity score matching (PSM) was performed to minimize the effects of confounding factors. Low ALC was defined as nadir of <0.33 × 103 cells/μL during CRT (top tertile). Univariate and multivariate logistic regression were used to identify predictors of low ALC nadir. Patients with immunotherapy had significantly higher ALC in the first 3 weeks during CRT and higher ALC nadir than those without. Overall survival was more favorable in patients with immunotherapy both before and after PSM. After a median follow-up of 12.1 months, patients with low ALC during CRT had a worse progression-free survival (PFS) (P = .026). In multivariate analysis, low ALC remained a significant prognostic factor for PFS. Planning target volume (PTV) and heart V5 were revealed to be independent predictors of low ALC. The addition of anti-PD-1 immunotherapy to definitive CRT could mitigate the decline of ALC during radiotherapy and might prolong survival. Low ALC nadir was correlated to worse PFS, larger PTV, and higher heart V5 in patients receiving combined immunotherapy and CRT.

Clinical utility of combined assessments of 4D volumetric perfusion CT, diffusion-weighted MRI and 18F-FDG PET-CT for the prediction of outcomes of head and neck squamous cell carcinoma treated with chemoradiotherapy

BackgroundMultiparametric imaging has been seen as a route to improved prediction of chemoradiotherapy treatment outcomes. Four-dimensional volumetric perfusion CT (4D PCT) is useful for whole-organ perfusion measurement, as it reflects the heterogeneity of the tumor and its perfusion parameters. However, there has been no study using multiparametric imaging including 4D PCT for the prognostic prediction of chemoradiotherapy. The purpose of this study was to determine whether combining assessments of 4D PCT with diffusion-weighted MRI (DWI) and 18F-fluorodeoxyglucose PET-CT could enhance prognostic accuracy in head and neck squamous cell carcinoma (HNSCC) patients treated with chemoradiotherapy.MethodsWe examined 53 patients with HNSCC who underwent 4D PCT, DWI and PET-CT before chemoradiotherapy. The imaging and clinical parameters were assessed the relations to locoregional control (LRC) and progression-free survival (PFS) by logistic regression analyses. A receiver operating characteristic (ROC) analysis was performed to assess the accuracy of the significant parameters identified by the multivariate analysis for the prediction of LRC and PFS. We additionally assessed using the scoring system whether these independent parameters could have a complementary role for the prognostic prediction.ResultsThe median follow-up was 30 months. In multivariate analysis, blood flow (BF; p = 0.02) and blood volume (BV; p = 0.04) were significant prognostic factors for LRC, and BF (p = 0.03) and skewness of the ADC histogram (p = 0.02) were significant prognostic factors for PFS. A significant positive correlation was found between BF and BV (ρ = 0.6, p < 0.001) and between BF and skewness (ρ = 0.46, p < 0.01). The ROC analysis showed that prognostic accuracy for LRC of BF, BV, and combination of BF and BV were 77.8%, 70%, and 92.9%, and that for PFS of BF, skewness, and combination of BF and skewness were 55.6%, 63.2%, and 77.5%, respectively. The scoring system demonstrated that the combination of higher BF and higher BV was significantly associated with better LRC (p = 0.04), and the combination of lower BF and lower skewness was significantly associated with worse PFS (p = 0.004).ConclusionA combination of parameters derived from 4DPCT and ADC histograms may enhance prognostic accuracy in HNSCC patients treated with chemoradiotherapy.

Nomogram Model for Predicting the Prognosis of High-Grade Glioma in Adults Receiving Standard Treatment: A Retrospective Cohort Study

To identify the critical factors associated with the progression-free survival (PFS) and overall survival (OS) of high-grade glioma (HGG) in adults who have received standard treatment and establish a novel graphical nomogram and an online dynamic nomogram. This is a retrospective study of adult HGG patients receiving standard treatment (surgery, postoperative radiotherapy, and temozolomide (TMZ) chemotherapy) at Huashan Hospital, Fudan University between January 2017 and December 2019. We used uni- and multi-variable COX models to identify the significant prognostic factors for PFS and OS. Based on the significant predictors, graphical and online nomograms were established. A total of 246 patients were enrolled in the study based on the inclusion criteria. The average PFS and OS were 22.99 ± 11.43 and 30.51 ± 13.73 months, respectively. According to the multi-variable COX model, age, extent of resection (EOR), and IDH mutation were associated with PFS and OS, while edema index (EI) was relevant to PFS. In addition, patients with IDH and TERT promoter co-mutations had longer PFSs and OSs, and no apparent survival benefit was found in the long-cycle TMZ adjuvant chemotherapy compared with the standard Stupp protocol. Based on these critical factors, a graphical nomogram and online nomogram were developed for predicting PFS and OS, respectively. The calibration curve showed favorable consistency between the predicted and actual survival rates. C-index and time-dependent AUC showed good discrimination abilities. We identified the significant predictors for the PFS and OS of HGG adults receiving standard treatment and established user-friendly nomogram models to assist neurosurgeons in optimizing clinical management and treatment strategies.

Pretreatment C-reactive protein-to-albumin ratio predicts clinical outcomes in patients with peripheral T-cell lymphoma.

Peripheral T-cell lymphoma (PTCL) is an aggressive and heterogenous T-cell lymphoid malignancy. The prognostic value of C-reactive protein-to-albumin ratio (CAR) has never been assessed in PTCL. This study retrospectively reviewed the medical records of 76 patients diagnosed with various subtypes of PTCL. A CAR cutoff value of 0.794 was determined, and clinical outcomes, including response rate, overall survival (OS), and progression-free survival (PFS), were compared between the high (> 0.794) and low (≤ 0.794) CAR groups. After induction therapy, complete response was achieved in 8 (32.0%) and 39 patients (76.5%) in the high and low CAR groups, respectively. During the median follow-up of 57.5months, the high CAR group had significantly worse 5-year PFS and 5-year OS rates. Even with adjustment for the International Prognostic Index (≥ 3), Prognostic Index for PTCL-unspecified (≥ 3), and T cell score (≥ 2), high CAR remained a significant prognostic factor for PFS (hazard ratio [HR]: 4.01, 95% confidence interval [CI] 2.04-7.86, p < 0.001) and OS (HR: 2.97, 95% CI: 1.33-6.64, p = 0.008). CAR may play a complementary role in predicting prognosis in patients with PTCL, considering its simplicity, objectivity, and easy accessibility.

Real-world first-line treatment of patients with BRAFV600E-mutant metastatic colorectal cancer: the CAPSTAN CRC study

BRAFV600E mutations occur in 8%-12% of metastatic colorectal cancer (mCRC) cases and are associated with poor survival. European guidelines recommend combination (doublet or triplet) chemotherapy plus bevacizumab in first line. However, an unmet need remains for more effective treatments for these patients. CAPSTAN CRC is a European, retrospective, multicenter, observational study evaluating real-world treatment practices for patients with BRAFV600E-mutant mCRC treated between 1 January 2016 and 31 January 2020. The primary objective was to describe first-line treatment patterns. Secondary objectives included describing baseline demographics, mutational testing procedures, treatment effectiveness, and safety. In total, 255 patients (median age 66.0 years; 58.4% female) with BRAFV600E-mutant unresectable mCRC from seven countries were included. Most had right-sided tumors (52.5%) and presented with synchronous disease at diagnosis (66.4%). Chemotherapy plus targeted therapy (68.7%) was preferred at first line over chemotherapy alone (31.3%). The main first-line treatments were FOLFOX plus bevacizumab (27.1%) and FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, irinotecan) with/without bevacizumab (27.1%/19.2%). Median duration of first-line treatment was 4.9 months. Overall, 52.5% received second-line treatment. Across all first-line regimens, progression-free survival (PFS) and overall survival were 6.0 [95% confidence interval (CI) 5.3-6.7] months and 12.9 (95% CI 11.6-14.1) months, respectively. Triplet plus targeted therapy was associated with more adverse events (75.0%) compared with triplet chemotherapy alone (50.0%) and doublet chemotherapy alone (36.1%). Multivariate analysis identified low body mass index and presence of three or more metastatic sites as significant prognostic factors for PFS. This study is, to date, the largest real-world analysis of patients with BRAFV600E-mutant mCRC, providing valuable insights into routine first-line treatment practices for these patients. The data highlight the intrinsic aggressiveness of this disease subgroup, confirming results from previous real-world studies and clinical trials, and stressing the urgent need for more effective treatment options in this setting.

The Effect of the Time Interval between Temozolomide and Radiotherapy in Adjuvant High-Grade Glioma Treatment

<h3>Purpose/Objective(s)</h3> The standard of care for high grade glioma (HGG) treatment consists of postoperative radiotherapy and temozolamide (TMZ). The effect of time between TMZ administration and RT on treatment outcomes is not well defined. The purpose of this study was to examine the interval between oral administration of TMZ and RT, and its effect on treatment outcomes in patients with HGG. <h3>Materials/Methods</h3> The clinical data of 277 patients with HGG treated between 2009 – 2021 at four centers were retrospectively analyzed. The following are the inclusion criteria: Pathologically proven grade ≥3 glial tumors, ≥18 years old, and completion of curative RT with concurrent oral 75 mg/m²/day TMZ. Patients who were unable to take oral TMZ, or had previously been treated with TMZ and/or RT were excluded. The TMZ to RT interval (TRI) was calculated from the time of oral TMZ administration to the time of RT fraction. In relation to the TMZ half-life, the interval time was divided into <2 h and ≥2 h groups. Progression free survival (PFS) is calculated as the time between the end of RT and clinical or radiological progression. Overall survival (OS) is calculated from the time of diagnosis to the last follow-up. <h3>Results</h3> The median age was 58 years (range: 19–81). 159 patients (57.4%) were male, while 118 (42.6%) were female. 75.4% of patients had an ECOG performance score (ECOG PS) of 0–1, and 54.5% had gross total resection (GTR). The median fraction and total RT doses were 2 Gy (1.8–3) and 60 Gy (40–60), respectively. The median follow-up was 15.2 months (range: 1.9–75.1) for the entire cohort. Two-year OS and PFS rates were 35% and 15%, respectively. After completion of RT, disease progression occurred in 255 patients (92.1%) at a median of 6.4 months (range, 0.2–64.9). The 2-year OS was 42.8% for patients with a TRI >2 hours and 32% for patients with a time interval of ≤2 hours (p = 0.18). Similarly, there was no statistically significant difference in 2-year PFS between the two groups (12.8% vs. 9%; p = 0.95). Age, ECOG PS, and type of surgery were all significant prognostic factors for OS and PFS in univariate analysis. In multivariate analysis, advanced age [HR = 1.03 (95% CI, 1.01 – 1.04); p<0.001], poor ECOG PS [HR = 2.14 (95% CI, 1.56 – 2.94); p<0.001], and incomplete surgical resection [HR = 1.39 (95% CI, 1.06–1.84); p = 0.02] were independent predictors of poorer OS. Similarly, age [HR = 1.02 (95% CI, 1.01 – 1.03); p = 0.002], ECOG PS [HR = 1.57 (95% CI, 1.17 – 2.09); p = 0.002], and type of surgery [HR = 1.41 (95% CI, 1.10 – 1.80); p = 0.006] were all significant prognostic factors for PFS in multivariate analysis. <h3>Conclusion</h3> We found that advanced age, poor performance status, and incomplete surgical resection were all predictive of poor OS and PFS in this current study. However, we were unable to detect a statistically significant effect of the time interval between oral administration of TMZ and RT. Validation of our findings will require a longer follow-up period and randomized trials.

Prognostic Value of 18F-Fluorodeoxyglucose-Positron Emission Tomography/Magnetic Resonance Imaging in Patients With Hypopharyngeal Squamous Cell Carcinoma.

The aim of the study is to investigate the value of pretreatment integrated positron emission tomography/magnetic resonance imaging (PET/MRI) in predicting the prognosis of patients with hypopharyngeal squamous cell carcinoma (HSCC). Twenty-one untreated patients with HSCC who underwent PET/MRI before treatment were enrolled. We analyzed the value of PET/MRI parameters in predicting the progression-free survival (PFS) and overall survival (OS) of HSCC patients. Kaplan-Meier method and log rank test were used to perform univariate survival analysis, whereas Cox proportional hazard regression models were used to perform multivariate analysis. Of the 21 patients with a median follow-up time of 20.3 months (range, 4.2-37.6 months), 2 (9.5%) had local recurrence, 2 (9.5%) had distant metastases, and 8 (38.1%) died because of cancer. Univariate analysis showed that T stage, clinical stage, total lesion glycolysis (TLG), and metabolic tumor volume (MTV) were significant prognostic factors for PFS (P < 0.05). T stage, clinical stage, TLG, MTV, the mean apparent diffusion coefficient (ADCmean), and the minimal apparent diffusion coefficient (ADCmin) were significant prognostic factors for OS (P < 0.05). The Cox proportional hazard regression model revealed that MTV was an independent prognostic factor for PFS, and TLG was an independent prognostic factor for OS (P < 0.05). Metabolic tumor volume was an independent predictor of PFS in patients with HSCC, while TLG was an independent predictor of OS. T stage, clinical stage, ADCmean, and ADCmin are potential prognostic indicators for HSCC. Positron emission tomography/magnetic resonance imaging can provide effective information for predicting the prognosis for HSCC patients.

Prognostic significance of STAT3 gene expression in patients with glioblastoma tumors: a study from Western India

ObjectiveGlioblastoma Multiforme (GBM), a devastating the most common primary malignant intracranial brain tumors. In India, the incidence of this malignancy is escalating, however, there are very few studies on this tumor entity from Indian population. The present study sought to investigate the prevalence and prognostic significance of Signal Transducer and Activator of Transcription 3 (STAT3) gene expression in GBM patients from Western India.MethodSTAT3 gene expression using real-time PCR was detected in total 55 GBM patients. The impact of STAT3 aberrant expression on progression-free survival (PFS) and overall (OS) was analysed using univariate and multivariate survival analysis. The data were analysed using SPSS statistical software and p value ≤0.05 was considered as significant.ResultsThe aberrant STAT3 expression was found in 85% (47/55) of patients with -1.12 fold change down-regulation in 49% (23/47) and 3.36 fold change up-regulation was noted in 51% (24/47) of patients. In wild type IDH tumors (n=30), down regulation and up regulation of STAT3 was noted in 63% and 27% of patients, respectively, whereas, for IDH mutant GBM tumors (n=25), the incidence of low expression and high expression of STAT3 was noted in 16% and 68% of patients, respectively. Thus, we found that incidence of STAT3 down regulation was significantly high in patients with IDH wild type tumors, whereas, in IDH mutant GBM tumors, the incidence of up-regulated STAT3 was significantly high (P=0.021, χ2=12.81, r=+0.310). In Kaplan-Meier univariate survival analysis, a part from age (P=0.006), tumor location (P=0.025), and KPS score (P=0.002), co-detection of STAT3 up regulation and presence of IDH mutation (P=0.030) remained significant prognostic factors for PFS and OS. In multivariate survival analysis also, co-detection of STAT3 high expression and presence of IDH mutation remained independent prognosticators for PFS (HR=6.45, 95% CI=1.32-31.40, P=0.021) and OS (HR=8.69, 95% CI=1.66-45.51, P=0.010).ConclusionFor GBM tumors, STAT3 up-regulation and presence of IDH mutations together predicts better survival. This reflects unique molecular etiology for GBM patients. Therefore, they would be useful in the future for targeted therapy and for clinicians they would be useful for better patient management. However, study on a larger sample size is required for validation.