Prognosis For Progression-free Survival Research Articles

25-Hydroxy vitamin D deficiency is an inferior predictor of peripheral T-cell lymphomas.

The aim of the study was to explore the significance and prognostic value of 25-hydroxy vitamin D (25-(OH) D) deficiency in peripheral T-cell lymphomas (PTCLs). One hundred fifty-six patients of newly diagnosed PTCLs were enrolled in the study. Univariate and multivariate regression analyses were performed to determine independent risk factors for progression-free survival (PFS) and overall survival (OS). Receiver operating characteristic (ROC) curves were plotted, and corresponding areas under the curve (AUC) were calculated to estimate the accuracy of International Prognostic Index (IPI) plus 25-(OH) D deficiency and Prognostic Index for T-cell lymphoma (PIT) plus 25-(OH) D deficiency respectively in PTCL risk stratification. Our results showed that the 25-(OH) D deficiency was an independent inferior prognostic factor for both PFS (P = 0.0019) and OS (P = 0.005) for PTCLs, especially for AITL and PTCL-not otherwise specified (PTCL-NOS). Additionally, adding 25-(OH) D deficiency to PIT indeed has a superior prognostic significance than PIT alone for PFS (P = 0.043) and OS (P = 0.036). Multivariate COX regression analysis revealed that PIT 2‒4, albumin (ALB) ≤ 35g/L, and 25-(OH) D deficiency were regarded as independent risk factors of PFS and OS. Our results showed that 25-(OH) D deficiency was associated with inferior survival outcome of PTCLs, especially for AITL and PTCL-NOS. PIT plus 25-(OH) D deficiency could better indicate the prognosis for PFS and OS of PTCLs than PIT.

Prognostic Significance of Programmed Cell Death Ligand 1 Expression in High-Grade Serous Ovarian Carcinoma: A Systematic Review and Meta-Analysis.

(1) Background: High-grade serous ovarian carcinoma (HGSOC) is an aggressive subtype of ovarian cancer. Recent advances have introduced prognostic markers and targeted therapies. Programmed cell death ligand 1 (PD-L1) has emerged as a potential biomarker for HGSOC, with implications for prognosis and targeted therapy eligibility; (2) Methods: A literature search was conducted on major databases, and extracted data were categorized and pooled. Subgroup analysis was performed for studies with high heterogeneity. (3) Results: Data from 18 eligible studies were categorized and pooled based on PD-L1 scoring methods, survival analysis types, and endpoints. The result showed an association between high PD-L1 expression and a favorable prognosis in progression-free survival (HR = 0.53, 95% CI = 0.35-0.78, p = 0.0015). Subgroup analyses showed similar associations in subgroups of neoadjuvant chemotherapy patients (HR = 0.6, 95% CI = 0.4-0.88, p = 0.009) and European studies (HR = 0.59, 95% CI = 0.42-0.82, p = 0.0017). In addition, subgroup analyses using data from studies using FDA-approved PD-L1 antibodies suggested a significant association between favorable prognosis and high PD-L1 expression in a subgroup including high and low stage data in overall survival data (HR = 0.46, 95% CI = 0.3-0.73, p = 0.0009). (4) Conclusions: This meta-analysis revealed a potential association between high PD-L1 expression and favorable prognosis. However, caution is warranted due to several limitations. Validation via large-scale studies, with mRNA analysis, whole tissue sections, and assessments using FDA-approved antibodies is needed.

Pretreatment 18F‐FDG uptake heterogeneity may predict treatment outcome of combined Trastuzumab and Pertuzumab therapy in patients with metastatic HER2 positive breast cancer

ObjectiveIntra-tumoral heterogeneity of 18F‐fluorodeoxyglucose (18F‐FDG) uptake has been proven to be a surrogate marker for predicting treatment outcome in various tumors. However, the value of intra-tumoral heterogeneity in metastatic Human epidermal growth factor receptor 2(HER2) positive breast cancer (MHBC) remains unknown. The aim of this study was to evaluate 18F‐FDG uptake heterogeneity to predict the treatment outcome of the dual target therapy with Trastuzumab and Pertuzumab(TP) in MHBC.MethodsThirty-two patients with MHBC who underwent 18F-FDG positron emission tomography/computed tomography (PET/CT) scan before TP were enrolled retrospectively. The region of interesting (ROI) of the lesions were drawn, and maximum standard uptake value (SUVmax), mean standard uptake value (SUVmean), total lesion glycolysis (TLG), metabolic tumor volume (MTV) and heterogeneity index (HI) were recorded. Correlation between PET/CT parameters and the treatment outcome was analyzed by Spearman Rank Test. The ability to predict prognosis were determined by time‐dependent survival receiver operating characteristic (ROC) analysis. And the survival analyses were then estimated by Kaplan‐Meier method and compared by log‐rank test.ResultsThe survival analysis showed that HI50% calculated by delineating the lesion with 50%SUVmax as threshold was a significant predictor of patients with MHBC treated by the treatment with TP. Patients with HI50% (≥ 1.571) had a significantly worse prognosis of progression free survival (PFS) (6.87 vs. Not Reach, p = 0.001). The area under curve (AUC), the sensitivity and the specificity were 0.88, 100% and 63.6% for PFS, respectively.Conclusion18F-FDG uptake heterogeneity may be useful for predicting the prognosis of MHBC patients treated by TP.

Effectiveness of D-Rd program in the first line therapy of a 75-year-old female patient with multiple myeloma with high-risk cytogenetics. Clinical observation

Multiple myeloma is a B-cell lymphoproliferative disorder. Morphological substrate of the disorder are plasma cells producing monoclonal immunoglobulin, and the disorder is characterized by heterogeneity of clinical manifestations. Due to the understanding of molecular and biological basics of multiple myeloma pathogenesis, significant success was achieved in treatment of the standard and high-risk cytogenetics groups including full remission. However, not all patients show long-term progression-free survival. Necessity of more accurate evaluation of the extent of antitumor response, prognosis of progression-free survival and recurrence development led to minimal residual disease (MRD) testing. The analysis is based on detection of phenotypically aberrant clonal plasma cells in bone marrow aspirate after drug treatment. Currently, MRD-negative status is a significant prognostic factor. In some studies, high effectiveness of daratumumab in achievement of MRD-negative status in elderly patients with newly diagnosed multiple myeloma was demonstrated.

A deep learning-based system for survival benefit prediction of tyrosine kinase inhibitors and immune checkpoint inhibitors in stage IV non-small cell lung cancer patients: A multicenter, prognostic study.

SummaryBackgroundFor clinical decision making, it is crucial to identify patients with stage IV non-small cell lung cancer (NSCLC) who may benefit from tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). In this study, a deep learning-based system was designed and validated using pre-therapy computed tomography (CT) images to predict the survival benefits of EGFR-TKIs and ICIs in stage IV NSCLC patients.MethodsThis retrospective study collected data from 570 patients with stage IV EGFR-mutant NSCLC treated with EGFR-TKIs at five institutions between 2010 and 2021 (data of 314 patients were from a previously registered study), and 129 patients with stage IV NSCLC treated with ICIs at three institutions between 2017 and 2021 to build the ICI test dataset. Five-fold cross-validation was applied to divide the EGFR-TKI-treated patients from four institutions into training and internal validation datasets randomly in a ratio of 80%:20%, and the data from another institution was used as an external test dataset. An EfficientNetV2-based survival benefit prognosis (ESBP) system was developed with pre-therapy CT images as the input and the probability score as the output to identify which patients would receive additional survival benefit longer than the median PFS. Its prognostic performance was validated on the ICI test dataset. For diagnosing which patient would receive additional survival benefit, the accuracy of ESBP was compared with the estimations of three radiologists and three oncologists with varying degrees of expertise (two, five, and ten years). Improvements in the clinicians’ diagnostic accuracy with ESBP assistance were then quantified.FindingsESBP achieved positive predictive values of 80·40%, 75·40%, and 77·43% for additional EGFR-TKI survival benefit prediction using the probability score of 0·2 as the threshold on the training, internal validation, and external test datasets, respectively. The higher ESBP score (>0·2) indicated a better prognosis for progression-free survival (hazard ratio: 0·36, 95% CI: 0·19–0·68, p<0·0001) in patients on the external test dataset. Patients with scores >0·2 in the ICI test dataset also showed better survival benefit (hazard ratio: 0·33, 95% CI: 0·18–0·55, p<0·0001). This suggests the potential of ESBP to identify the two subgroups of benefiting patients by decoding the commonalities from pre-therapy CT images (stage IV EGFR-mutant NSCLC patients receiving additional survival benefit from EGFR-TKIs and stage IV NSCLC patients receiving additional survival benefit from ICIs). ESBP assistance improved the diagnostic accuracy of the clinicians with two years of experience from 47·91% to 66·32%, and the clinicians with five years of experience from 53·12% to 61·41%.InterpretationThis study developed and externally validated a preoperative CT image-based deep learning model to predict the survival benefits of EGFR-TKI and ICI therapies in stage IV NSCLC patients, which will facilitate optimized and individualized treatment strategies.FundingThis study received funding from the National Natural Science Foundation of China (82001904, 81930053, and 62027901), and Key-Area Research and Development Program of Guangdong Province (2021B0101420005).

Abstract 642: Spatial analysis of tumor infiltrating lymphocytes in histological images using deep learning predicts progression-free survival in colorectal cancer

Abstract Histological distribution and density of tumor infiltrating lymphocytes (TILs) are known to be informative to cancer patients’ outcome. However, due to the heterogeneity and huge size of digitized pathology slides, it has been a challenging problem to quantify TILs-related features in whole slide images (WSI). This study aimed to explore the impact of spatial distribution of TILs quantified by deep learning (DL) approaches based on digitalized WSI stained with hematoxylin and eosin in patients with colorectal cancer (CRC). The cancer and TILs regions are first separately identified by deep learning models in the WSI. The TILs densities at tumor invasive margins are then quantified by image analysis algorithms and used for prognosis of progression-free survival (PFS) in CRC patients. The prognostic impact of spatial distributions of TILs in CRC patients was explored in the Yonsei cohort (n=180) and validated in the TCGA cohort (n=268). Two experienced pathologists manually measured TILs at the most invasive margin as 0-3 by the Klintrup-Mäkinen (KM) grading method and compared to DL approaches. On multivariate analysis, TILs densities within 200µm of the invasive margin (f_im200) was remained as the most significant prognostic factor for PFS (HR 0.004 [95% CI, 0.0001-0.1502], p=.002) in the Yonsei cohort. On multivariate analysis using the TCGA dataset, f_im200 retained prognostic significance for PFS (HR 0.031, [95% CI 0.001-0.645], p=.024). Inter-observer agreement of manual KM grading was insignificant in both cohorts. The survival analysis by pathologists’ manual KM grading showed statistically significant different PFS from the TCGA cohort, but not the Yonsei cohort. In summary, automated quantification of TILs at the invasive margin showed a prognostic utility to predict PFS, and could provide reproducible TILs density measurement in CRC patients. Citation Format: Hongming Xu, Yoon Jin Cha, Jean Clemenceau, Jinhwan Choi, Sung Hak Lee, Jeonghyun Kang, Tae Hyun Hwang. Spatial analysis of tumor infiltrating lymphocytes in histological images using deep learning predicts progression-free survival in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 642.

Augmented alpha-beta PSMA radioligand therapy in metastatic prostate cancer: Analysis of prognostic factors for survival.

e17025 Background: PSMA-targeted radioligand therapy (PRLT) using the alpha-emitter Ac-225 PSMA-617 is effective in metastatic prostate cancer progressing after beta-emitter-based PRLT using Lu-177 PSMA-617, and in the presence of diffuse bone marrow metastases. Xerostomia is a dose-limiting factor in PRLT using Ac-225. Augmented Alpha-Beta PRLT is a concept of concomitantly administering Lu-177 and Ac-225 PSMA in lower activities, as a trade-off between efficacy and the dose-limiting toxicity, i.e., xerostomia. The objective of this study was to compare overall survival (OS), progression-free survival (PFS), and incidence of xerostomia among metastatic prostate cancer patients who received Ac-225 PSMA-617 augmentation in the initial phase of Lu-177 PSMA-617 RLT compared to those who received it in the late phase. Initial phase is defined as first two cycles of PSMA radioligand therapy (PRLT) vs late phase as after two cycles. We also examined prognostic factors associated with OS and PFS. Methods: Kaplan Meier method was used to examine survival curves and log-rank tests were conducted to examine differences in survival by groups. Cox Proportional Hazard (CPH) model was used to examine the impact of bone marrow and visceral metastasis and age on OS and PFS. Progression was defined as an increase of ≥ 25% in prostate-specific antigen (PSA) levels. Results: 68 patients who received Ac-225 PSMA-617 by itself, or Ac-225 PSMA-617 augmentation to Lu-PSMA-617 were included in the analysis. Out of these, 15 received early augmentation, 50 received late augmentation, and 3 received Ac-225 PSMA-617 alone. Of these, 48 experienced cancer progression and 21 died due to cancer progression. Median OS was 47 months and PFS was 11 months. Those who received early augmentation had significantly better PFS (median PFS not reached during study period) compared to those who received late augmentation (median PFS: 9 months) (p = 0.02). Early augmentation was associated with lower likelihood of xerostomia (p = 0.09). CPH model suggested that visceral or bone marrow metastasis were associated with significantly worse prognosis for PFS (p = 0.04). Conclusions: In patients progressing after Lu-177 PSMA radioligand therapy and those with diffuse bone-marrow metastases, an earlier augmentation with Ac-225 PSMA-617 is associated with better PFS and lower side effects such as xerostomia. Having visceral or bone marrow metastasis is a poor prognostic indicator for PFS in augmented alpha-beta PSMA radioligand therapy.

Role of Homologous Recombination Repair (HRR) Genes in Uterine Leiomyosarcomas: A Retrospective Analysis.

Simple SummaryA more in-depth molecular characterization of uterine leiomyosarcomas (uLMS), a rare disease characterized with dismal prognosis, could provide data suitable for the identification of potential target-based drugs. We aimed to define frequencies of gene alterations in uLMS, especially regarding the somatic mutations of BRCA and HRR gene alterations, and identify the impact of these molecular alterations on clinical outcomes. This retrospective analysis of the mutational profile of uLMS showed that the most frequent alterations involved the TP53 gene, and that patients with TP53 alterations experienced a worse prognosis compared to patients with wild-type TP53 genes. Conversely, patient clinical outcomes were similar within patients with BRCA- and HRR-related genes versus non-HRR-related genes. However, although the frequency of patients with BRCA- and HRR-related alterations and mutations was relatively small, this setting could deserve an investigation into drug actionability, and potentially benefit from PARP inhibitors.Uterine leiomyosarcomas (uLMS) is a very rare disease, and patients experience a dismal prognosis even when treated with chemotherapy. Therefore, a more in-depth molecular characterization of this disease could provide suitable data for the identification of potential target-based drugs. This retrospective, single institutional study aimed to define the frequencies of gene alterations in uLMS, especially regarding the somatic mutations of BRCA and Homologous Recombination Repair (HRR) genes, and the impact of molecular alterations on clinical outcomes. The 16-genes Next-Generation Sequencing (NGS) panel, Homologous Recombination Solution TM (HRS, Sophia Genetics, Saint Sulpice, Switzerland), was used for the molecular evaluation of samples. The majority of patients (66/105, 63%) carried at least one sequence alteration, with a prevalence of TP53 involvement followed by RAD51B, BRCA1/2, and FANCL. Patients with TP53 gene alterations experienced a significantly worse prognosis for progression free survival (PFS) and overall survival (OS) versus wild-type patients. Given the number of patients with the BRCA1/2 mutation (N = 12), we included them in the HRR patient group; there was no difference in clinical outcomes with HRR versus non-HRR. The Cox’s multivariate analysis showed that stage and TP53 gene alterations resulted in a significantly worse OS. The integration of gene networking data, such as tumor mutation burdens and cancer driver gene identification, could show a clearer discrimination of gene distribution patterns, and lead to the implementation of therapeutic targets.

Maintenance Intervention Improves Survival in Patients With Metastatic Nasopharyngeal Carcinoma Who Benefit From First-Line Treatment: A Prospective Multicenter Randomized Controlled Clinical Study

The progression-free survival (PFS) of metastatic nasopharyngeal carcinoma after first-line chemotherapy is not ideal, and the role of drug maintenance intervention in improving survival outcomes remains controversial. To investigate the safety and effect of Tegafur(S1) maintenance intervention in patients with metastatic nasopharyngeal carcinoma who benefit from the first-line treatment in a multicenter randomized controlled study, and to identify the related biological prognostic factors and guide the individualized treatment choice.Patients with metastatic nasopharyngeal carcinoma in the Fourth Affiliated Hospital of Guangxi Medical University and other cancer centers who met the inclusion criteria were randomly divided into maintenance therapy group: S1 maintenance therapy until disease progression or intolerance; Observation group: follow-up to disease progression. PFS, overall survival (OS) and adverse reactions of S1 maintenance therapy were compared between the two groups. The correlation between EBV-DNA, human serum amyloid A (SAA) and prognosis was evaluated.Follow-up was conducted to May 2020, with a median follow-up of 19.8 months (6.1-51.3 months), 183 cases were evaluable (88 cases in S1 maintenance treatment group, 95 cases in observation group). Compared with the observation group, the S1 maintenance treatment group significantly increased patients' median PFS (16.2 months vs. 8.7 months, P < 0.001) and median OS (32.1 months vs. 18.2 months, P < 0.001). Reduced the risk of poor prognosis for PFS and OS (PFS: HR 0.305, 95% CI 0.211-0.441, < 0.001; OS: HR 0.363, 95% CI 0.238-0.553, P < 0.001). In the maintenance treatment group, the median S1 treatment lasted for 14 courses (4-58 courses), and the main adverse reactions were grade 1 skin pigmentation, oral mucositis, hand-foot syndrome, nausea, etc. No grade 4 toxic reaction occurred, and it was well tolerated. Compared with observation patients with negative EBV-DNA, observation patients with positive EBV-DNA had a higher risk of poor prognosis for PFS (HR 1.764, 95% CI 1.078-2.887, P = 0.024). The risk of poor prognosis in patients with positive EBV-NDA was significantly reduced by 61.1% (< 0.001) for PFS and 65.5% (P = 0.001) for OS (P = 0.001). Compared with the observation group with stable SAA expression, S1 maintenance therapy significantly improved the prognosis of patients. Patients with continuous decline in SAA had a 61.9% lower risk of poor prognosis in PFS (P < 0.001) and a 60.2% lower risk of poor prognosis in OS (P = 0.007).For patients with metastatic nasopharyngeal carcinoma who benefit from first-line treatment, maintenance therapy of S1 can significantly improve the survival prognosis and is well tolerated. Patients with positive EBV-DNA and continuous decline in SAA may benefit more from maintenance intervention.

Comprehensive assessment of the systemic and local immunity, inflammatory factors and clinical indicators in patients with gastric cancer

Objective.To study the state of cellular immunity and local immunity in patients with gastric adenocarcinoma.Materials and methods.From 2017 to 2018 45 primary patients with gastric adenocarcinoma (25 — with stages I–III, 20 — with stage IV) received surgical / combined treatment or chemotherapy at the Blokhin Scientific Research Center of Oncology, respectively. Peripheral blood and tumor tissue were collected before starting treatment. The percentage of the degree of infiltration of tumor tissue by lymphocytes (CD45 + CD14‑TILs) was assessed by flow cytometry: T‑cells (CD3 + CD19‑TILs), B‑cells (CD3‑CD19 + TILs), NK‑cells (CD3‑CD16 + CD56 + TILs), effector cells CD16 and CD8 and their cytotoxic potential (CD16 + Perforin + TILs, CD16CTPTILs), (CD8 + Perforin + TILs; CD8CTPTILs); subpopulations of regulatory T‑cells — NKT‑cells (CD3 + CD16 + CD56 + TILs), regulatory CD4‑cells (CD4 + CD25 + CD127‑TILs) and CD8 (CD8 + CD11b‑CD28‑TILs) and parameters of systemic immunity.Intratumoral and stromal subpopulations of CD4 + TILs, CD8 + TILs, CD4 + / CD8 + TILs ratios were studied by immunohistochemistry. Also, the cellular composition of peripheral blood was investigated. The prognostic significance of immune cells, inflammation factors (neutrophil‑lymphocyte index, platelet‑lymphocyte index) and clinical characteristics (patient»s age (both by years and by groups: up to 45 years, 46–60 years, over 60 years), disease stage, differentiation (G), Lauren type and MSI status were evaluated for overall survival (OS) and progression‑free survival (PFS).Results.The factor of a favorable prognosis for PFS in patients with local and locally advanced forms of gastric cancer was an increase in the number of CD3 + CD19‑TILs (HR0.865, 95 %CI 0.782–0.957, p = 0.005), and for poor prognosis — an increase in NK‑cells; HR1.382, 95 %CI 1.087–1.758, p = 0.008. There was a negative effect of the relative content of NK‑cells, an increase in the level of neutrophils in the peripheral blood on the OS of patients with metastatic GC (HR1.42, 95 %CI 1.06–1.89, p = 0.017 and HR1.64, 95 %CI 1.12–2.40, p = 0.011). At the same time, an increase in the age of patients, the level of neutrophils and platelets (HR1.106, 95 %CI 1.002–1.199, p = 0.015; HR1.714, 95 %CI 1.063–2.764, p = 0.027 and HR1.017, 95 %CI 1.006–1.029, p = 0.003) reduce PFS in patients with metastatic gastric cancer.Conclusion.Indicators of local immunity, the cellular composition of peripheral blood, characterizing the systemic inflammatory response, as well as indicators of systemic immunity can serve as additional prognostic factors in gastric cancer.

Androgen receptor splice variant 7 detected by immunohistochemical is an independent poor prognostic marker in men receiving adjuvant androgen-deprivation therapy after radical prostatectomy

BackgroundTo evaluate the predictive value of AR-V7 expression detected by immunohistochemical (IHC) in the prognosis of prostate cancer patients receiving adjuvant hormonal therapy (AHT) following radical prostatectomy (RP).MethodsWe retrospectively collected data of 110 patients with prostate cancer receiving RP, followed by AHT, from Tongji hospital. IHC analysis of AR-V7 expression was performed in a retrospective cohort.ResultsIn total, 110 patients were enrolled, of whom 21 patients (19.1%) were AR-V7-positive and 89 patients (80.9%) were AR-V7-negative. No significant differences in baseline characteristics were found between the two groups. AR-V7-positive patients had shorter progression-free survival (PFS) (HR: 4.26; 95% CI, 1.55 to 11.68; P = 0.003), shorter cancer-special survival (CSS) (HR: 22.47; 95% CI, 2.912 to 173.4; P = 0.003) and shorter overall survival (OS) (HR: 6.61; 95% CI, 1.40 to 31.20; P = 0.017) compared to AR-V7-negative patients. In multivariate analysis, AR-V7 is an independent risk factor for shorter PFS (HR, 3.76; 95% CI, 1.63 to 8.70; P = 0.002), shorter CSS (HR: 9.17; 95% CI, 1.48 to 55.56; P = 0.017) and shorter OS (HR: 4.81; 95% CI, 1.28 to 17.86; P = 0.020).ConclusionThe presence of AR-V7 in prostate cancer tissue is independently associated with an unfavorable prognosis for PFS, OS and CSS in patients who received AHT.

Value of tube combined with real-time ultrasound-guided accurate interstitial high-dose-rate brachytherapy for post-operative pelvic side-wall recurrences of cervical cancer.

PurposeTreatment of post-operative pelvic side-wall relapses of cervical cancer has always been a therapeutic challenge for radiation oncologists. Radiation dose boost to recurrent tumor by brachytherapy is necessary, but difficult to achieve. Our treatment center has successfully achieved precise transvaginal insertion of a pelvic side-wall mass, using a metal tube with real-time ultrasound guidance. This study investigates the efficacy and safety of image-guided high-dose-rate (HDR) interstitial brachytherapy (IBT) for patients with post-operative pelvic side-wall relapses.Material and methodsBetween 2018 and 2020, 36 post-operative pelvic side-wall relapses of cervical cancer patients receiving external beam radiotherapy (EBRT) combined with HDR-IBT were analyzed retrospectively. Doses per fraction ranged from 6.0 to 7.0 Gy, whereas cumulative equivalent doses in 2 Gy fractions ranged from 80 to 100 Gy. Effects of prognostic factors on local control (LC) and progression-free survival (PFS) were analyzed, and late toxicity data were evaluated.ResultsA total of thirty-six patients were included, with a median follow-up of 19.3 months. The tumor response was obtained for all patients, with radiological complete remission in 20 (55.6%) patients. Two-years LC and PFS rates were 72.2% and 47.2%, respectively. Grade II rectal toxicity was observed in 5 patients (13.9%). Multivariate analyses for LC and PFS using proportional regression model were performed, in which shape of exophytic tumor was associated with a significantly better prognosis for both LC and PFS (HR = 0.071, 0.128, p = 0.005, 0.002). Clinical target volume (CTV) D90 remained associated with a significantly better prognosis for PFS (HR = 0.056, p = 0.000).ConclusionsA metal tube placed in the vagina, under the guidance of real-time ultrasound in transvaginal IBT for pelvis masses can be accurately achieved. The shape of exophytic tumor and CTV D90 were associated with a significantly better prognosis for PFS, and the shape of exophytic tumor was also associated with a better prognosis for LC. Therefore, radiation dose boost using IBT can improve the prognosis of patients with post-operative pelvic side-wall recurrences of cervical cancer.

Circulating Tumour DNA Is an Independent Prognostic Biomarker for Survival in Metastatic BRAF or NRAS-Mutated Melanoma Patients.

Circulating tumour DNA (ctDNA) can be used to identify gene alterations. The purpose of this study was to determine whether the detection of ctDNA, based on the identification of BRAF and NRAS mutations before systemic treatment initiation, was associated with the prognosis of metastatic melanoma. In total, 68 BRAF or NRAS-mutated stage IV or unresectable stage III metastatic cutaneous melanoma patients were included and tested for the presence of BRAF and NRAS mutations in circulating DNA before treatment initiation, using the Cobas BRAF/NRAS Mutation Test (Roche). The expected mutation was detected in the plasma of 34/68 patients (50% sensitivity). ctDNA detection was associated with AJCC stage, along with the number and nature of metastases. ctDNA was less frequently detected in NRAS-mutated than in BRAF-mutated melanoma (36% and 66%, respectively). At initiation of first-line treatment, ctDNA detection was associated with poor prognosis in Progression Free Survival (PFS) and Overall Survival (OS) in univariate analysis (log-rank: p = 0.002 and p < 0.0001, respectively). In multivariate analysis, ctDNA detection was an independent factor of poor prognosis in OS, after adjustment for AJCC stage, number and nature of metastases and gender (HR = 4.384; 95% CI: (1.308; 14.699); p = 0.017).

Analysis of the prognostic factors of triple-negative breast cancer and the clinical efficacy of postoperative radiotherapy in early cases.

e12502 Background: To explore the prognostic value of pretherapeutic peripheral blood parameters and breast imaging-reporting and data system (BI-RADS) classification of triple-negative breast cancer (TNBC) and the effect of postoperative radiotherapy in early cases. Methods: A total of 278 TNBC patients’ medical records between January 2013 and December 2018 were retrospectively collected, including white blood cells, neutrophils, lymphocytes, platelets, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), serum tumor markers, BI-RADS classification, TNM staging and therapeutic methods. We used the log-rank test and Kaplan-Meier curves to assess the progression-free survival (PFS) of enrolled patients. Multivariate prognostic analysis was performed by the Cox regression model. Results: The median PFS of all 278 patients was 20 months (4-72 months) at the end of follow-up. Operable patients who obtained adjuvant chemotherapy had a better median PFS (20 vs 18.5 months, P= 0.018, HR = 5.943, 95% CI: 1.36-25.92) than those without. Lymph node metastasis (52%) and chest well relapse (28%) were the critical failure forms followed by other metastases (12% lungs, 9.3% bones, 4% liver and 2.7% brain) with p value less than 0.001. Multivariate analysis indicated that platelet counts &gt; 113.5×109/L (p = 0.024), PLR ≤ 111.7 (p = 0.036) and CA15-3 ≤ 8.4 U/mL (p = 0.003) were significantly associated with the favourable prognosis of PFS in TNBC patients. Furthermore, BI-RADS of grade 2-4 had a better median PFS compared with grade of 5-6(20 vs 17.5 months, p = 0.008, HR = 2.154, 95% CI: 1.219-3.805). In subgroup analysis, forty-three early cases with pN1 stage earned additional benefits from postoperative radiotherapy in terms of low risk of distant metastasis and recurrence (p = 0.014). Residual tumor after surgery was another important factor of poor prognosis (p = 0.029). Conclusions: Adjuvant chemotherapy improved median PFS for operable TNBC patients and pretherapeutic platelets, PLR, CA15-3 and BI-RADS were the independent prognostic factors of survival. Lymph node metastasis and chest well relapse were the main patterns of treatment failure. Radiotherapy could reduce the risk of disease progression for postoperative patients with N1 stage.

Differential population screening and efficacy analysis of (125)I implantation after radiofrequency ablation of primary liver cancer

Objective: To investigate the clinical efficacy radiofrequency ablation (RFA) combined with (125)I radioactive seed implantation in treatment of hepatocellular carcinoma HCC with the tumor diameter 3-5 cm. Methods: One hundred patients with HCC diagnosed clinically or pathologically with Barcelona staging of B or C in Lishui Central Hospital from February 2012 to September 2017 were retrospectively analyzed. Of the included 100 cases, 89 were males and 11 were females with the mean age of 18-80 (57±11) years old.According to the treatment modality, the subjects were divided into control group (RFA, n=67) and combined group (RFA+(125)I, n=33). Patients in control group were only received RFA and cases in combined group received RFA plus sequenced with (125)I implantation therapy. The prognosis of progression free survival (PFS) and overall survival (OS) between the two groups were compared through the Kaplan-Meier curve and Log-rank test. Results: The median follow-up time period was 6-55 months in the last follow-up time point of Dec 30, 2017. The median PFS were 4-55 (23.0±4.7) and 1-53 (12.0±1.6) months for combined and control groups respectively with significant statistical difference (P=0.015). The median OS were 6-55 (42.0±7.9) and 2-55 (38.0±2.8) months for combined and control groups with the trend of improvement in combined group, but without statistical difference (P=0.444). Subgroup analysis further indicated that the PFS was significant improved in patients with residual tumor lesions who received the combined treatment (PFS: 18 vs 9 months, P=0.025). However, there was no statistical difference for PFS between the control and combined treatment groups for cases without residual tumor lesions after RAF treatment(P=0.685). Conclusions: PFS was obviously increased in HCC patients(tumor diameter 3-5 cm) who received(125)I implantation after radiofrequency ablation, especially for cases with residual tumor lesions.

Enhancing the Critical Role of Core Needle Biopsy in Breast Cancer

The aim of this literature review is to derive detailed information on the significance of core needle biopsy in the diagnosis and effective treatment of breast cancer, according to current evidence, in an era of targeted therapy dependent on breast cancer stage and subtype. Preoperative diagnosis by core biopsy is rendered obligatory due to its crucial role not only in precise surgical management but also in segregating patients that often present with complete pathologic response (pCR) after neoadjuvant chemotherapy (NAC). Even in the absence of pCR, proper therapeutic management of these patients show significantly better prognosis in progression free survival (PFS) and overall survival (OS).

Significance of Chromogranin A in Diagnosis and Prognosis of Neuroendocrine Tumors

We present the comparative study of plasma chromogranin A (CgA) levels measured in 232 patients with different types of neuroendocrine tumors (NETs) and 66 healthy individuals using enzyme immunoassay Chromogranin A ELISA kit (Dako). CgA levels were significantly higher in patients with all types of NETs than in healthy subjects. CgA secretion were highly variable. The study demonstrate high diagnostic sensitivity of CgA, which was 80.6 % in overall group of NETs with specificity 98.5 %. We confirmed the prognostic significance of CgA, in this case the high basal levels of CgA (above 100 U/l) were significantly associated with less favorable prognosis of progression free survival after different types of treatment. The data confirms high efficiency of CgA as biomarker, which measurement enhances the accuracy of diagnosis and prognosis of NETs.

Clinical and prognostic effects of CDKN2A, CDKN2B and CDH13 promoter methylation in ovarian cancer: a study using meta-analysis and TCGA data

Background: Promoter methylation of tumour suppressor genes (TSGs) CDKN2A, CDKN2B and CDH13 has been reported in ovarian cancer. However, the clinicopathological characteristics and prognostic role of CDKN2A, CDKN2B and CDH13 promoter methylation in ovarian carcinoma remained unclear.Methods: The pooled odds ratio (OR) or hazard ratios (HRs) with their 95% confidence intervals (95% CIs) were calculated in this meta-analysis. The Cancer Genome Atlas data were obtained to confirm the role of CDKN2A, CDKN2B and CDH13 methylation in ovarian cancer.Results: CDKN2A, CDKN2B and CDH13 promoter methylation was higher in ovarian cancer than in normal ovarian tissues. CDH13 promoter methylation was correlated with tumour histology (serous vs. non-serous type: OR = 0.33, p = 0.031). CDKN2A promoter methylation was not linked to overall survival (OS), but it was correlated with a poor prognosis in progression-free survival (HR = 1.55, p = 0.004). TCGA data showed no correlation between CDKN2A, CDKN2B and CDH13 methylation and OS as well as disease-free survival (DFS).Conclusions: CDKN2A, CDKN2B and CDH13 promoter methylation may correlate with the increased risk of ovarian cancer. CDKN2A promoter methylation may be an independent prognostic biomarker for predicting progression-free survival.

Prediction of outcome in anal squamous cell carcinoma using radiomic feature analysis of pre-treatment FDG PET-CT

PurposeIncidence of anal squamous cell carcinoma (ASCC) is increasing, with curative chemoradiotherapy (CRT) as the primary treatment of non-metastatic disease. A significant proportion of patients have locoregional treatment failure (LRF), but distant relapse is uncommon. Accurate prognostication of progression-free survival (PFS) would help personalisation of CRT regimens. The study aim was to evaluate novel imaging pre-treatment features, to prognosticate for PFS in ASCC.MethodsConsecutive patients with ASCC treated with curative intent at a large tertiary referral centre who underwent pre-treatment FDG-PET/CT were included. Radiomic feature extraction was performed using LIFEx software on baseline FDG-PET/CT. Outcome data (PFS) was collated from electronic patient records. Elastic net regularisation and feature selection were used for logistic regression model generation on a randomly selected training cohort and applied to a validation cohort using TRIPOD guidelines. ROC-AUC analysis was used to compare performance of a regression model encompassing standard clinical prognostic factors (age, sex, tumour and nodal stage—model A), a radiomic feature model (model B) and a combined radiomic/clinical model (model C).ResultsA total of 189 patients were included in the study, with 145 in the training cohort and 44 in the validation cohort. Median follow-up was 35.1 and 37. 9 months, respectively for each cohort, with 70.3% and 68.2% reaching this time-point with PFS. GLCM entropy (a measure of randomness of distribution of co-occurring pixel grey-levels), NGLDM busyness (a measure of spatial frequency of changes in intensity between nearby voxels of different grey-level), minimum CT value (lowest HU within the lesion) and SMTV (a standardized version of MTV) were selected for inclusion in the prognostic model, alongside tumour and nodal stage. AUCs for performance of model A (clinical), B (radiomic) and C (radiomic/clinical) were 0.6355, 0.7403, 0.7412 in the training cohort and 0.6024, 0.6595, 0.7381 in the validation cohort.ConclusionRadiomic features extracted from pre-treatment FDG-PET/CT in patients with ASCC may provide better PFS prognosis than conventional staging parameters. With external validation, this might be useful to help personalise CRT regimens in the future.

The Role of 18-Fluoro-2-Deoxy-Glucose Positron Emission Tomography/Computed Tomography as Response and Prognosis Predictive Factor of Concurrent Chemoradiotherapy after Induction Chemotherapy in Head and Neck Squamous Cell Carcinoma: A Prospective Study.

Background and objectives: The importance of induction chemotherapy (ICT) followed by concurrent chemoradiotherapy (CCRT) has been re-established in recent years aiming at fewer metastatic sites and better control of the disease. We prospectively studied the possibility of early prediction of overall survival (OS) and progression-free survival (PFS) after 3 cycles of chemotherapy with doxetacel, cisplatin and 5-fluorouracil using 18-fluoro-2-deoxy-glucose positron emission tomography computed tomography (18F-FDG PET/CT) in patients with head and neck squamous cell cancer. To our knowledge, this is the first such study. Materials and Methods: Thirty-five patients were studied. They underwent an 18F-FDG PET/CT examination twice: a day before ICT and 10–14 days after the last cycle of ICT. Tumor-standardized uptake value (SUVmax) and hypermetabolic tumor volume were measured on both scans. The mean age of patients was 56.5 years. Complete responses to CCRT PFS and OS were calculated. Results: Our results showed that a decrease of ≥30% in the SUVmax value after ICT was a prognostic factor of tumor response to PFS and OS (p = 0.026 and p = 0.021). The groups of patients with a SUVmax between 10 and 14.5 in the primary tumor on a pre-ICT 18F-FDG PET/CT scan had statistically shorter PFS and OS (p = 0.001, p = 0.006) when compared with other groups of patients with SUVmax less than 10 or SUVmax more than 14.5. A decrease of less than 55% of hypermetabolic tumor volume of the primary tumor was significantly related to poor prognosis in PFS and OS (p = 0.033, p = 0.017). Conclusions: SUVmax and hypermetabolic tumor volume measured on 18F-FDG PET/CT after ICT might be valuable prognostic tools for predicting OS and PFS and, thus, for the selection of patients with head and neck cancer who will benefit from CCRT.