Significant Difference In Progression-free Survival Research Articles

Exploring the impact of BRCA1 and BRCA2 mutation type and location on Olaparib maintenance therapy in platinum-sensitive relapsed ovarian Cancer patients: A single center report

ObjectiveIn patients with platinum-sensitive relapsed ovarian cancer (PSROC) harboring pathogenic/likely pathogenic variants (PV) in BRCA1 and BRCA2 genes, olaparib maintenance monotherapy (OMT) is a viable option. Our study aimed to evaluate the impact of different BRCA1/2 PV in survival outcomes and safety of OMT in BRCA1/2-mutated PSROC patients, focusing on the type and location of PV. MethodsWe assessed the outcomes of 100 BRCA1/2-mutated PSROC patients treated at our institute, analyzing progression-free survival (PFS) and overall survival (OS). Germline and tumor BRCA1/2 genotyping was conducted using Illumina's next-generation sequencing (NGS). ResultsPFS and OS were significantly shorter in PSROC patients with PV in BRCA1 compared to those with PV in BRCA2 (PFS:14.0 vs. 38.8 months, p = 0.007, OS: 21.8 vs. 62.0 months, p = 0.011). Notably, there was a significant difference in PFS based on the intragenic location of BRCA1 PV, with shorter PFS in patients with 1st/2nd relapse, harboring PV in BRCA1 RING domain compared to those with PV in the DNA binding domain (DBD) and BRCT domains (12.4 vs. 23.0 months, p = 0.046). No differences in PFS and OS were observed between patients with germline versus somatic BRCA1/2 PV (PFS:14.9 vs.19.3, p = 0.316, OS: not reached vs. 25.8 months; p = 0.224). However, there were significant differences in the reasons for OMT discontinuation between patients with germline and somatic BRCA1/2 PV, primarily due to adverse side effects. ConclusionsIn summary, the type and location of BRCA1 and BRCA2 PV provide additional insight into the expected survival outcomes of olaparib MT in PSROC patients.Trial registration number: ISRCTN42408038, Name of registry: ISRCTN registry, Date of registration: 24/11/2015.

A Translational Study of the ATR Inhibitor Berzosertib as Monotherapy in Four Molecularly Defined Cohorts of Advanced Solid Tumors.

Preclinical studies have identified molecular correlates of sensitivity to ATR inhibition. This translational study was designed to test the ATR inhibitor berzosertib in patients with advanced solid tumors carrying alterations in ATRX, ATM, genes conferring replication stress (RS), or SDH. Patients were recruited to 4 cohorts: T1: ATRX-mutant leiomyosarcoma; T2: ATM-mutant solid tumors; T3: solid tumors with mutations in RS-associated genes; and T4: SDH-deficient GIST. Patients were treated with berzosertib 240 mg/m2 IV twice per week. Pre and on-treatment biopsies were obtained in cohorts T1-T3. Patients with SDH-mutant GIST had the longest median progression-free survival (PFS) (229 days) with stable disease as the best response. Patients in the other cohorts experienced progressive disease within 4 months. There was no significant difference in PFS comparing outcomes in patients with/without mutations in ATM or RS genes. Decreased pS345-CHK1 in on-treatment biopsies indicated target engagement by berzosertib and were accompanied by substantial increases in levels of DNA damage (g-H2AX) and RS (pKAP1) markers in a subset of patients. However, these biomarker changes did not translate to clinical benefit. In contrast, in cohorts T1-T3, increased expression of SFLN11 on treatment correlated with clinical benefit (HR = 0.045; 95%CI 0.005-0.400). Across cohorts, only SDH-mutant GIST patients experienced prolonged disease control. Despite evidence of target engagement, patients enrolled to all other cohorts had short PFS, suggesting rapid adaptation to ATR inhibitor monotherapy. Among these patients, those with tumors expressing SLFN11 during berzosertib exposure derived the most clinical benefit.

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.

Comparative Analyses of the Outcomes Between Lobectomies and Trisegmentectomies/Lingulectomies in the Surgical Management of Clinical Stage I Left Upper Lobe Non-small Cell Lung Cancer.

Lobectomies are the standard surgical intervention for lung cancer; however, recently, surgeons have considered segmentectomies for smaller tumors, with their potential for favorable survival outcomes while preserving lung function. The surgical outcomes of trisegmentectomies/lingulectomies and lobectomies for clinical stage I left upper lobe (LUL) non-small cell lung cancers (NSCLCs) remain undetermined. Thus, our study aimed to assess the differences between the short-term surgical and long-term survival outcomes in patients with clinical stage I LUL NSCLC who underwent trisegmentectomies/lingulectomies and those who underwent lobectomies. Between 2011 and 2021, we retrospectively reviewed the data of 377 patients with clinical stage I NSCLC who had undergone LUL lobectomies or trisegmentectomies/lingulectomies. Patients were categorized into two subcohorts according to tumor size, i.e. 0-2 and 2-4 cm. To ensure preoperative demographic comparability, 1:1 propensity-score matching (PSM) was performed. This study focused on the 2-4cm subcohort. Post-PSM, patients who underwent trisegmentectomies/lingulectomies had quicker operations and shorter postoperative hospital and intensive care unit lengths of stay than those who underwent lobectomies. Post-PSM, no statistically significant differences in progression-free survival (PFS) or overall survival (OS) were observed between the segmentectomy and lobectomy groups in both the0-2 and 2-4cm subcohorts. The multivariate analysis revealed that different surgical methods were not statistically significant factors for either PFS or OS. Trisegmentectomies/lingulectomies are a feasible option for clinical stage I NSCLC, with better perioperative outcomes and similar survival rates when compared with LUL lobectomies.

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.

Choosing the optimal therapy for metastatic renal cell carcinoma: Insights from a real-world comparative study.

The evolution of combination therapies integrating immune checkpoint inhibitors has revolutionized the first-line treatment of metastatic renal cell carcinoma (mRCC). Although these therapies are clinically approved, direct comparisons between dual immune checkpoint inhibitors (IOIO) and immune checkpoint inhibitors combined with tyrosine kinase inhibitors (IOTKI) in clinical trials are lacking. This gap creates uncertainties in selecting the most appropriate treatment based on patient-specific factors. This study employed the inverse probability of treatment weighting (IPTW) method to analyze progression-free survival (PFS) and overall survival (OS) for patients with mRCC receiving IOIO or IOTKI treatment regimens. A total of 171 patients were analyzed after applying inclusion criteria and propensity scoring. The study found no significant differences in PFS and OS between the two treatment modalities in the IPTW cohort. However, subgroup analyses revealed that IOTKI therapy was associated with better PFS and OS for patients without bone metastases and better OS for patients with a body mass index (BMI) over 25. IOIO therapy showed better OS for patients with a BMI below 18.5. Both IOIO and IOTKI therapies were effective. Therapy selection could be better tailored to patient characteristics by including factors such as the presence of bone metastases and BMI. This study enhances understanding of how patient-specific factors interact with different treatment modalities, potentially guiding more personalized treatment decisions in clinical practice for mRCC.

TERT promoter mutations and survival outcomes in adult-type granulosa cell tumors

ObjectivesT0 evaluate survival outcomes among patients with adult-type granulosa cell tumors who have telomerase reverse transcriptase (TERT) promoter mutations.MethodsThis is a retrospective cohort study using the MD Anderson Rare Gynecologic...

Impact of low HER2 expression on response to CDK4/6 inhibitor treatment in advanced HR + /HER2- breast cancer: a multicenter real-world data analysis.

CDK4/6 inhibitors (CDK4/6i) represent the first-line therapy approach of choice for patients with hormone receptor-positive, HER2-negative advanced breast cancer (HR + /HER-ABC). Approximately 50% of HR + /HER2-ABC displays low HER2 expression (HER2 low). Recent data emerging from the DESTINY-Breast04 trial demonstrated practice-changing efficacy of the antibody-drug conjugate trastuzumab deruxtecan (T-DXd) in patients with low HER2 expression. Here, we aimed to analyze the impact of low HER2 expression on CDK4/6i therapy response in a well-characterized multicenter HR + /HER-ABC cohort. Patients diagnosed with HR + /HER2-ABC who were treated with CDK4/6i in clinical routine between November 2016 and December 2020 at four certified German Breast Cancer Centers were retrospectively identified. The cohort was stratified according to graduation of positivity in HER2 immunohistochemistry (IHC; HER2 zero = IHC score 0 and HER2 low = IHC score 1 + , 2 + /fluorescence in situ hybridization negative). Subgroups were analyzed with regard to progression-free survival (PFS) following CDK4/6i initiation. The study cohort comprised n = 448 patients. For n = 311 patients, HER2 status from the metastatic site was available. n = 91 (29.3%) cases were HER2 zero and n = 220 cases (70.7%) were HER2 low. There was no significant difference in PFS between the two groups (PFS: 17months versus 18months, log-rank p = 0.42). Further, we examined the influence of HER2 expression changes between primary and metastatic tissue (n = 171; HER2 gain/HER2 loss/HER2 stable expression) on CDK4/6i treatment response. Again, there was no significant difference between these three groups, respectively (PFS: 16months versus 13months versus 17months, log-rank p = 0.86). In our analysis, HER2 status did not have a significant impact on treatment response to CDK4/6i.

8785 Does Somatostatin Receptor Expression Intensity Impact Prognosis in Non Pituitary Neuroendocrine Tumors Treated with Somatostatin Analogues?

Abstract Disclosure: N. Saleh Jouneghani: None. S. Fazeli: None. S. Chang: None. A. Hosseini: None. R. Marandi: None. A. Siddiqui: None. M. Talley: None. B. Salehian: None. Does Somatostatin Receptor Expression Intensity Impact Prognosis in Non Pituitary Neuroendocrine Tumors Treated with Somatostatin Analogues? Introduction: Non-pituitary neuroendocrine tumors (NETs) show different somatostatin receptor subtype (SSTR) expression, but their role in tumor progression and prognosis is not well known. We hypothesized that NETs with higher expression of SSTR2, SSRT5, or co-expression of SSTR2 and SSTR5 will have better outcome when treated with Somatostatin Analogues (SSA). Method: Retrospectively, patients with non-pituitary neuroendocrine tumors, followed for more than one year between 1985 and 2022, and treated with SSA (Octreotide or Lanreotide) who had available tissue were selected. Tissue immunostaining performed for SSTR2 and SSTR5 with use of monoclonal antibodies. Expression analysis of the SSTR2 and SSTR5 were evaluated by the validated semi-quantitatively method, reported by an intensity score of 0 -3. The progression free survival and overall survival were calculated by Kaplan Meier and compared in different subgroups with SSTR expression intensity. Response evaluation was assessed using RECIST v1.1. Results: Of 279 non-pituitary neuroendocrine tumors, 51 meet the criteria and tissue sent for analysis. The median age at diagnosis was 62; male 49%, with median follow up 7 years, 85% stage IV at diagnosis, most common primary tumor was in gut 54% followed by pancreas 33%. Positive SSRT5 tumors had 93% SSRT2 co-expression. There were no significant differences in progression-free survival (PFS) observed between tumors with low or high SSTR2 intensity expression (P=0.62). The presence or absences of SSRT5 expression did not have any impact on PFS (p=0.57) or overall survival (p=0.3). Conclusion: in the patient with non-pituitary neuroendocrine tumors, higher SSTR2 expression intensity or having SSRT5 co-expression, did not correlate with a better PFS or overall survival in response to SSA, in our study. Further prospective studies are needed to clarify if higher expression intensity of SSRTs correlates with better response to SSAs in NETs. Presentation: 6/1/2024

Impact of instrumentation material on local recurrence: a case-matched series using carbon fiber-PEEK vs. titanium.

Spine metastases are a major burden of oncologic care, contributing to substantial morbidity. A well-established treatment paradigm for patients with metastatic epidural spinal cord compression includes separation surgery followed by stereotactic body radiotherapy (SBRT). Innovations in implant technology have brought about the incorporation of Carbon fiber-reinforced polyetheretherketone (CFR-PEEK) instrumentation for spinal fixation. We present our experience of CFR-PEEK instrumentation, comparing outcomes and complication profiles with a matched cohort of titanium instrumented cases for spine metastatic disease. Oncology patients who underwent spinal fusion for metastatic spine disease from 2012 to 2023 were retrospectively reviewed. Ninety-nine cases with CFR-PEEK fusions were case-control matched with 50 titanium controls (2:1 ratio) based upon primary tumor type and spinal instability neoplastic score (SINS) location. Demographic, clinical, radiographic and progression free survival (PFS) were analyzed. In the study years, 263 patients underwent spinal decompression and fusion, for which 148 patients met predetermined inclusion criteria. Of these, 49 had titanium instrumentation, and 99 had CFR-PEEK. Complication profiles, including hardware failure and infection were similar between the groups. There was no significant difference in PFS between all CFR-PEEK and titanium patients (143 days versus 214 days; p = 0.41). When comparing patients in which recurrence was noted, CFR-PEEK patients had recurrence detected two times earlier than titanium patients (94 days versus 189 days; p = 0.013). In this case matched cohort, CFR-PEEK demonstrated decreased overall PFS suggestive of earlier local recurrence identification. Long-term studies are warranted for better evaluation of the impact on survival and systemic disease progression.

Utilizing Clinical Transformation Criteria for Prognostic Stratification in Follicular Lymphoma Prior to Initial Immunochemotherapy.

Although the prognosis of follicular lymphoma (FL) has improved, some patients experience early disease progression, including progression of disease within 24 months (POD24). Histological transformation is a critical event in FL. However, the heterogeneity of FL tumors makes it challenging to diagnose transformation accurately. We retrospectively applied the clinical transformation criteria used for FL transformation assessments at relapse or disease progression to conduct transformation assessments before the initial immunochemotherapy. Sixty-six FL patients who first received immunochemotherapy between January 2009 and February 2023 at our institution were selected. Twenty-three were clinical-transformation-positive (CLT+). The progression-free survival (PFS) rate of the CLT+ patients was significantly lower than that of the clinical-transformation-negative (CLT-) patients. In the POD24 assessment subgroup, the CLT+ patients had a higher incidence of POD24 than the CLT- patients. There was no significant difference in PFS between the patients treated with CHOP-like regimens and those treated with bendamustine regimens. In the CHOP-like group, the CLT+ patients exhibited significantly lower PFS than the CLT- patients. In the bendamustine group, the clinical transformation did not affect PFS. Clinical transformation criteria may be useful for the prognostic stratification of FL prior to immunochemotherapy. Additionally, they may serve as predictors of POD24.

Immune checkpoint inhibitors with or without radiotherapy in metastatic non‑small cell lung cancer: A meta‑analysis and literature review.

The combination of immune checkpoint inhibitors (ICIs) and radiotherapy has shown promise in the treatment of metastatic non-small cell lung cancer (NSCLC). The present meta-analysis aimed to determine the efficacy and safety of combining radiotherapy (RT) ICIs for the treatment of metastatic NSCLC. PubMed, Google Scholar, the Cochrane Library and Web of Science databases were searched for relevant articles up to February 1, 2023. Post-therapy outcomes such as progression-free survival (PFS), complete response, partial response (PR), progressive disease (PD), stable disease and adverse events (AEs) were analyzed. The meta-analysis was performed using RevMan 5.4 software. A total of seven studies involving 682 patients were included (384 patients who received ICI + RT vs. RT and 298 patients who received ICI + RT vs. ICI alone). No significant difference in PFS was demonstrated between the ICI + RT group and the RT group (heterogeneity: χ2=2.35; df=1; P=0.13; I2=57% and test for overall effect: Z=0.10; P=0.92). Conversely, patients in the ICI alone group had significantly decreased PR rates (heterogeneity: Τ2=0.00; χ2=2.13; df=3; P=0.54; I2=0% and test for overall effect: Z=2.57; P=0.01) compared with patients in the ICI + RT group. The ICI + RT group also had significantly lower rates of PD (heterogeneity: Τ2=0.00; χ2=0.91; df=3; P=0.82; I2=0% and test for overall effect: Z=2.52; P=0.01) compared with the ICI alone group. Safety analysis revealed no significant difference between patients who received ICI + RT and those who received RT in terms of grade 1 or 2 AEs. In conclusion, the combination of ICIs + RT demonstrates promising efficacy and safety for patients with metastatic NSCLC. However, clinical trials that have tested this combination are lacking, which emphasizes the need for further research.

Para-aortic and pelvic lymphadenectomy in locally advanced cervical cancer with pelvic lymph node metastasis

ObjectiveThis study sought to explore the efficiency of para-aortic and pelvic lymphadenectomy in the treatment of locally advanced cervical cancer (LACC) with pelvic lymph node (PLN) metastasis.MethodsA total of 171 LACC patients with imaging-confirmed pelvic lymph node metastasis were included in this study. These patients were divided into two groups: the surgical staging group, comprising 58 patients who had received para-aortic and pelvic lymphadenectomy (surgical staging) along with concurrent chemoradiation therapy (CCRT), and the imaging staging group, comprising 113 patients who had received only CCRT. The two groups’ progression-free survival (PFS), overall survival (OS) and treatment-related complications were compared.ResultsThe surgical staging group started radiotherapy 10.2 days (range 9–12 days) later than the imaging staging group. The overall incidence of lymphatic cysts was 9.30%. In the surgical staging group, para-aortic lymph node metastasis was identified in 34.48% (20/58) of patients, while pathology-negative PLN was observed in 12.07% (7/58). Over a median follow-up period of 52 months, no significant differences in PFS and OS rates were found between the two groups (p > 0.05). Subgroup analysis of patients with lymph node diameters of ≥ 1.5 cm revealed a five-year PFS rate of 75.0% and an OS rate of 80.0% in the surgical staging group, compared to 41.5% and 50.1% in the imaging staging group, respectively, showing statistically significant differences (p = 0.022, HR:0.34 [0.13, 0.90] and p = 0.038, HR: 0.34 [0.12,0.94], respectively for PFS and OS). Additionally, in patients with two or more metastatic lymph nodes, the five-year PFS and OS rates were 69.2% and 73.1% in the surgical staging group, versus 41.0% and 48.4% in the imaging staging group, with these differences also being statistically significant (p = 0.025, HR: 0.41[0.19,0.93] and p = 0.046, HR: 0.42[0.18,0.98], respectively).ConclusionPerforming surgical staging before CCRT is safe and delivers accurate lymph node details crucial for tailoring radiotherapy. This approach merits further investigation, particularly in women with pelvic lymph nodes measuring 1.5 cm or more in diameter or patients with two or more imaging-positive PLNs.Graphical

Prognostic impact of body mass index on metastatic HER2-positive breast cancer survival

Background. The association between body mass index and prognosis in patients with HER2-positive metastatic breast cancer (mBC) is unclear. Purpose – the first purpose of our study was to determine whether BMI is an independent prognostic factor for progression-free survival (PFS) and overall survival (OS) in HER2-positive mBC patients. The second objective was to assess the mutual impact of baseline clinicopathological characteristics on survival outcomes. Materials and Methods. The study group included patients treated at the Sumy Regional Clinical Oncology Center. We considered the underweight patients if their BMI was <18.5 kg/m2, normal weight 18.5–24.9 kg/m2, overweight 25.0–29.9 kg/m2, and obese ≥ 30 kg/m2. The following formula was used for calculations: weight/height2 (kilograms/meter2). Information about the height, weight, and other clinicopathological characteristics of the patient at the time of the start of drug therapy was taken from the primary medical documentation. Pearson’s test and Chi2 test for categorical variables were used to compare baseline clinicopathological characteristics in groups with normal, overweight, and obesity. The Kaplan-Meier method was used to establish the medians of PFS and OS. Cox regression analysis assessed the mutual impact on the survival of various clinicopathological characteristics. The statistical significance threshold was considered P ≤0.05. Results. Seventy-eight patients with HER2-positive mBC were enrolled and categorized according to their BMI in normal weight, overweight, and obese groups. BMI had a different impact on PFS and OS. Median PFS was 14.9, 11.9, and 14.2 months for normal-weight, overweight, and obese patients, respectively. There is no statistically significant difference in PFS between groups (Р = 0.110). Multivariable regression analysis confirmed no impact of BMI on PFS. Nevertheless, metastases in bones and kidneys and the nuclear grade were statistically significant determinants of PFS. Median OS was 26.4, 28.8, and 37.9 months for normal-weight, overweight, and obese patients, respectively. BMI, kidney metastases, and nuclear grade were prognostically significant determinants of OS. Conclusions. BMI is an independent prognostic factor of OS in patients with HER2-positive mBC. Obesity is associated with better OS but does not impact PFS. Metastases in bones and kidneys and the nuclear grade can predict survival outcomes.

TBI/Cy followed by auto-HSCT is a good choice next to allo-HSCT for patients with T-LBL/ALL

The aim of this retrospective study was to evaluate the efficiency and safety of total body irradiation plus cyclophosphamide (TBI/Cy) followed by autogenetic hematopoietic stem cell transplantation (auto-HSCT) in T-LBL/ALL patients that cannot receive allogeneic hematopoietic stem cell transplant (allo-HSCT). Between 2013 and 2023, 24 patients received auto-HSCT following by TBI/Cy, 26 patients underwent allo-HSCT, all patients achieved completed hematopoietic reconstitution after HSCT. The progression free survival (PFS) and overall survival (OS) had no statistically significant differences between the two groups (P = 0.791, HR 1.127, 95%CI 0.456–2.785; P = 0.456, HR 0.685, 95%CI 0.256–1.828). Although the cumulative incidence of relapse was lower for patients who received allo-HSCT than auto-HSCT (P = 0.033, HR 3.707, 95%CI 1.188–11.570, 2-year relapse 11.5% vs. 33.3%), the incidence of non-relapse mortality (NRM) was higher than that in the auto-HSCT group (P = 0.014, HR 0.000, 95%CI -1.000 - -1.000, 2-year NRM, 23.1% vs. 0%). Trough Landmark analysis, the two groups showed a statistically significant difference in 3-year PFS and 4-year OS curves (Figure S2A&B, P = 0.039, HR 0.426, 95%CI 0.163–1.117; P = 0.014, HR 0.317, 95%CI 0.113–0.887). By COX analysis, poor baseline performance status (ECOG-PS ≥ 2) and CNS involvement were risk factors for PFS and OS. In conclusion, TBI/Cy followed by auto-HSCT is a good choice next to allo-HSCT for patients with T-LBL/ALL.

Recurrence pattern of glioblastoma treated with intensity-modulated radiation therapy versus three-dimensional conformal radiation therapy.

To evaluate recurrence patterns of and survival outcomes in glioblastoma treated with intensity-modulated radiation therapy (IMRT) versus three-dimensional conformal radiation therapy (3D-CRT). We retrospectively examined 91 patients with glioblastoma treated with either IMRT (n = 60) or 3D-CRT (n = 31) between January 2013 and December 2019. Magnetic resonance imaging showing tumor recurrence and planning computed tomography scans were fused for analyzing recurrence patterns categorized as in-field, marginal, and out-of-field based on their relation to the initial radiation field. The median overall survival (OS) was 18.9 months, with no significant difference between the groups. The median progression-free survival (PFS) was 9.4 months, with no significant difference between the groups. Patients who underwent gross total resection (GTR) had higher OS and PFS than those who underwent less extensive surgery. Among 78 relapse cases, 67 were of in-field; 5, marginal; and 19, out-of-field recurrence. Among 3D-CRT-treated cases, 24 were of in-field; 1, marginal; and 9, out-of-field recurrence. Among IMRT-treated cases, 43 were of in-field; 4, marginal; and 10, out-of-field recurrence. In partial tumor removal or biopsy cases, out-of-field recurrence was less frequent in the IMRT (16.2%) than in the 3D-CRT (36.3%) group, with marginal significance (p = 0.079). IMRT and 3D-CRT effectively managed glioblastoma with no significant differences in OS and PFS. The survival benefit with GTR underscored the importance of maximal surgical resection. The reduced rate of out-of-field recurrence in IMRT-treated patients with partial resection highlights its potential utility in cases with unfeasible complete tumor removal.

Alpha-fetoprotein and des-gamma-carboxy prothrombin can predict the objective response of patients with hepatocellular carcinoma receiving durvalumab plus tremelimumab therapy.

Durvalumab plus tremelimumab (Durva/Treme) combined immunotherapy is the first-line therapy recommended for unresectable hepatocellular carcinoma (HCC). Since sequential therapy is more effective in improving prognosis, tumor markers have been used as predictive biomarkers for response to systemic therapy. This study aimed to investigate the predictive ability of objective response (OR) by tumor markers for Durva/Treme therapy against HCC. In this multicenter study, 110 patients with HCC who received Durva/Treme therapy were retrospectively enrolled. The OR rate was 15.5%. To aid early decision-making regarding OR, we evaluated the predictors contributing to OR in two steps: before (first step) and 4 weeks after (second step) treatment induction. Changes in tumor markers (alpha-fetoprotein [AFP] and des-gamma-carboxy prothrombin [DCP]) from baseline to 4 weeks after treatment (ΔAFP/ΔDCP) were included as the input factors. In the first step, multivariable analysis identified only the baseline AFP level (odds ratio 3.497, p = 0.029) as a predictor of OR. Patients with AFP ≥ 400 ng/mL had a significantly higher OR rate than those with < 400 ng/mL (28.2 vs. 8.5%, p = 0.011), and there was no significant difference in progression-free survival (PFS) between the two groups. When AFP/DCP response was defined as a ≥10% reduction from baseline, multivariable analysis showed that AFP response (odds ratio 6.023, p = 0.042) and DCP response (odds ratio 11.657, p = 0.006) were both independent predictors of OR in the second step. The PFS of patients with AFP or DCP response was significantly longer than that of patients without AFP or DCP response. The study demonstrated that the use of AFP and DCP can predict the OR of patients with HCC receiving Durva/Treme therapy.

Fertility-sparing treatment with conization versus radical hysterectomy in patients with early-stage cervical cancer: inverse propensity score weighted analysis

ObjectiveTo report 20 years of experience with fertility-sparing surgery for patients with early-stage cervical cancer, comparing the oncological outcomes with outcomes for those who underwent a radical hysterectomy.MethodsPatients with pre-operative...

Baseline eosinophil proportion is a useful predictor of immune-related adverse events following immune checkpoint inhibitor treatment for recurrent metastatic head and neck cancer

Background Immune checkpoint inhibitors (ICIs) occasionally cause immune-related adverse events (irAEs) in various organs. However, predictors of irAEs remain unidentified. Objectives We evaluated the predictors of irAEs and compared the outcomes of ICIs with and without irAEs in patients with recurrent/metastatic head and neck cancers (R/M HNCs). Materials and methods We retrospectively analyzed 157 patients with R/M HNCs who were administered an anti-PD-1 antibody between September 2014 and December 2022. We examined whether various pretreatment factors were associated with irAEs. The overall survival (OS) and progression-free survival (PFS) in patients with and without irAEs were analyzed. Results Overall, 44 patients (28.0%) developed irAEs. The survival curve estimated for patients with and without irAEs showed a significant difference in PFS (p = 0.018), but not in OS (p = 0.208). Multivariate analysis revealed significant differences in relative eosinophil counts (p < 0.001), TP (p = 0.014), and NLR (p = 0.002), which may be independent predictors of irAEs. Conclusion IrAEs may be associated with higher efficacy of ICIs and longer PFS. The relative eosinophil count may be predictors of irAEs and useful in routine medical practice. Using these biomarkers to predict irAEs will help predict ICI effects and manage irAEs.

Effectiveness of combined targeted and hormonal therapies for post-menopausal women with hormone receptor-positive and HER2-negative advanced breast cancer: A systematic review and meta-analysis of RCTs.

we aim to synthesize available evidence on the effectiveness of hormonal plus targeted therapies for post-menopausal women with hormone receptor-positive and HER2-negative advanced breast cancer. We searched the following databases: Medline, PubMed, Cochrane Library, CINAHL, Web of Science, Scopus, and African Journal. Only studies that investigated the effectiveness of hormonal therapy combined with targeted therapy for HR+/HER2- advanced breast cancer treatment were included. The outcomes were progression-free survival (PFS), overall survival (OS) and objective response rate (ORR). A random-effect meta-analysis model was employed. Statistical analysis was performed using Comprehensive Meta-analysis version 3. 24 studies were included in the meta-analysis with an overall sample size of 7635. Median PFS, OS and ORR were found to be significantly increased in the combination group compared to hormonal monotherapy [SMD = 6.072 (95% CI = 3.785-8.360), p < 0.001], [SMD = 1.614 (95% CI = 0.139-3.089), p = 0.032] and [OR = 1.584 (CI 1.134-2.213), p = 0.007] respectively. Subgroup analysis showed a significant difference in PFS and ORR between patients who received "hormonal therapy + CDK4/6 inhibitors" vs hormonal therapy only [SMD = 6.015 (CI 3.069-8.960), p < 0.001], (OR = 1.828 (CI 1.030-3.243), p = 0.039] respectively. Compared with hormonal monotherapy, targeted plus hormonal therapy significantly improves PFS, OS and ORR in postmenopausal women with HR+/HER2- advanced breast cancer.