Disease-free Survival In Group Research Articles

CD7 Chimeric Antigen Receptor T-Cell Therapy Bridging to Allogeneic Hematopoietic Stem Cell Transplantation Remarkably Improved Long-Term Disease-Free Survival in Refractory/Relapsed T-Cell Acute Lymphoblastic Leukemia/Lymphoma

Introduction: The prognosis of refractory/relapsed T-cell acute lymphoblastic leukemia/lymphoma (r/r T-ALL/LBL) is poor, and salvaged allogeneic hematopoietic stem cell transplantation (allo-HSCT) can only result in 20%-30% disease-free survival (DFS). Our previous clinical trials have shown that the patients with r/r T-ALL have achieved 90% complete remission (CR) with CD7 chimeric antigen receptor T cell (CART) therapy (Pan J. et al. JCO 2021), then quick received allo-HSCT to obtain 57% of 1-year DFS in 12 patients (Li ZH. et al. Transplantation and Cellular Therapy 2022). Objectives : In current study, the long-term outcomes of allo-HSCT in r/r T-ALL/LBL after CD7 CART therapy in larger cohort are investigated, and compared with that chemotherapy only before allo-HSCT simultaneously. The risk factors for prognosis after allo-HSCT in this setting are also analyzed. Methods: Between February 2018 and January 2023, total 90 patients with r/r T-ALL/LBL who underwent allo-HSCT in our hospital were included. The median age was 14 (2-65) years old. Somatic and germline gene mutations were detected by sequencing pre-transplant. Thirty-two (35.6%) patients were sensitive to chemotherapy and achieved CR before transplant (group A), and 58 (64.4%) cases were resistant to chemotherapy and in non-remission (NR) pre-HSCT. Forty-one of 58 patients in NR received CD7 CART before allo-HSCT (group B) and the rest 17 patients in NR underwent salvaged transplant (group C). Donor types included haploidential (60, 66.7%), unrelated (16, 17.8%) and identical sibling (14, 15.6%). Myeloablative conditioning regimens with either total body irradiation (TBI)/fludarabine (51, 56.7%) based or busulfan/fludarabine (39, 43.3%) based were applied. Antithymocyte globulin was used for haploidentical and unrelated transplants. Cyclosporine, mycophenolate mofetil and short-term methotrexate were employed for graft-versus-host disease (GVHD) prophylaxis. Results: All patients achieved durable engraftment. No significant difference was found in the incidences of acute GVHD (aGVHD), chronic GVHD (cGVHD) and infections in 3 groups (p=0.612, p=0.091, p=0.649). With a median follow-up of 25.5 (19.6-32) months, 2-year overall survival (OS) in group B was similar to that in group A (54.4% vs. 69.9%, p=0.33) and much higher than that in group C (35.3%, p=0.0065), and 2-year DFS in group B was similar to that in group A (51.0% vs. 61.1%, p=0.24) and much higher than that in group C (17.6%, p=0.0029). No statistical difference was seen on transplant-related mortality (TRM) (17.3% vs. 9.8% vs. 11.8%, p=0.65) among group B, A, C. Two-year cumulative incidence of relapse in group B (31.7%) was similar to group A (29.0%), and much lower than that in group C (70.5%). The risk for relapse and death decreased remarkably in group B (p=0.0047) and group A (p=0.0003) compared with that in group C. NR before transplant (p=0.0062), aGVHD (p=0.013) and viral infections (p=0.047) were risk factors for relapse-related death, but TBI-based conditioning (p=0.01) was positive impact factor on OS. The most common somatic gene mutations were NOTCH 1(55.7%), JAK 3 (18.0%), TP53 (16.4%), JAK1 (14.8%) and N R AS(14.8%). The most common germline gene mutations were EP300 (10.3%), ATM (8.6%), F7 (8.6%), KIT (8.6%) and N CF2 (8%). The patients with somatic TP53 or MED12 mutation had significantly higher risk for relapse and death (p=0.0018, p=0.0068). Germline gene mutations had no significant influence on prognosis post-transplant. Multivariate analysis had shown that CD7 CART (p=0.037), TBI-based conditioning (p=0.002) and cGVHD (p=0.004) were independent positive impact factors on OS, but aGVHD (p=0.034) and TP53 mutation (p=0.002) were independent negative impact factors for OS. Meanwhile, CD7 CART (p=0.005) and TBI-based conditioning (p=0.024) had positive impact on DFS, but TP53 mutation (p=0.02) also had negative impact on DFS. Conclusion s : Our study has demonstrated that CD7 CART followed by allo-HSCT has remarkably improved long-term DFS for chemotherapy-resistant T-ALL/LBL, and achieved comparable results in safety and efficacy with chemotherapy-sensitive disease post-transplant. Our study has also shown the profiles of somatic and germline gene mutations in r/r T-ALL/LBL, and identified some positive and negative impact factors for prognosis after transplant in this setting.

Long-Term Oncologic Outcomes in Robot-Assisted and Video-Assisted Lobectomies for Non-Small Cell Lung Cancer.

This study compares long-term outcomes in patients undergoing video-assisted thoracic surgery (VATS) and robotic-assisted thoracic surgery (RATS) lobectomy for non-small cell lung cancer (NSCLC); all consecutive patients who underwent RATS or VATS lobectomy for NSCLC between July 2015 and December 2021 in our center were enrolled in a single-center prospective study. The primary outcomes were overall survival (OS), disease-free survival (DFS), and recurrence rate. The secondary outcomes were complication rate, length of hospitalization (LOS), duration of chest tubes (LOD), and number of lymph node stations harvested. A total of 619 patients treated with RATS (n = 403) or VATS (n = 216) were included in the study. There was no significant difference in OS between the RATS and VATS groups (3-year OS: 75.9% vs. 82.3%; 5-year OS: 70.5% vs. 68.5%; p = 0.637). There was a statistically significant difference in DFS between the RATS and VATS groups (3-year DFS: 92.4% vs. 81.2%; 5-year DFS: 90.3% vs. 77.6%; p < 0.001). Subgroup analysis according to the pathological stage also demonstrated a significant difference between RATS and VATS groups in DFS in stage I (3-year DFS: 94.4% vs. 88.9%; 5-year DFS: 91.8% vs. 85.2%; p = 0.037) and stage III disease (3-year DFS: 82.4% vs. 51.1%; 5-year DFS: 82.4% vs. 37.7%; p = 0.024). Moreover, in multivariable Cox regression analysis, the surgical approach was significantly associated with DFS, with an HR of 0.46 (95% CI 0.27-0.78, p = 0.004) for RATS compared to VATS. VATS lobectomy was associated with a significantly higher recurrence rate compared to RATS (21.8% vs. 6.2%; p < 0.001). LOS and LOD, as well as complication rate and in-hospital and 30-day mortality, were similar among the groups. RATS lobectomy was associated with a higher number of lymph node stations harvested compared to VATS (7 [IQR:2] vs. 5 [IQR:2]; p < 0.001). In conclusion, in our series, RATS lobectomy for lung cancer led to a significantly higher DFS and significantly lower recurrence rate compared to the VATS approach. RATS may allow more extensive nodal dissection, and this could translate into reduced recurrence.

Prediction model on disease recurrence for low risk resected stage I lung adenocarcinoma.

Although stage I non-small cell lung carcinoma (NSCLC) typically carries a good prognosis following complete resection, early disease recurrence can occur. An accurate survival prediction model would help refine a follow-up strategy and personalize future adjuvant therapy. We developed a post-operative prediction model based on readily available clinical information for patients with stage I adenocarcinoma. We retrospectively studied the disease-free survival (DFS) of 408 patients with pathologically confirmed low-risk stage I adenocarcinoma of lung who underwent curative resection from 2013 to 2017. A tree-based method was employed to partition the cohort into subgroups with distinct DFS outcome and stepwise risk ratio. These covariates were included in multivariate analysis to build a scoring system to predict disease recurrence. The model was subsequently validated using a 2011-2012 cohort. Non-smoker status, stage IA disease, epidermal-growth factor receptor mutants and female gender were associated with better DFS. Multivariate analysis identified smoking status, disease stage and gender as factors necessary for the scoring system and yielded 3 distinct risk groups for DFS [99.4 (95% CI 78.3-125.3), 62.9 (95% CI 48.2-82.0), 33.7 (95% CI 24.6-46.1) months, p < 0.005]. External validation yielded an area under the curve by receiver operating characteristic analysis of 0.863 (95% CI 0.755-0.972). The model could categorize post-operative patients using readily available clinical information, and may help personalize a follow-up strategy and future adjuvant therapy.

A prognostic score from a multicentric retrospective analysis of patients affected by sarcoma with metachronous lung metastases undergoing metastasectomy.

Despite the lack of evidence-based on prospective randomized studies, surgery has become the cornerstone of the treatment in patients with pulmonary oligometastatic sarcomas. Our study aimed to construct a composite prognostic score for metachronous oligometastatic sarcoma patients. A retrospective analysis was performed on data patients who underwent radical surgery for metachronous metastases in sixresearch institutes from January 2010 to December 2018. The log-hazard ratio (HR) obtained from the Cox model was used to derive weighting factors for a continuous prognostic index designed to identify differential outcome risks. A total of 251 patients were enrolled in the study. In the multivariate analysis, a longer disease-free interval (DFI) and a lower neutrophil-to-lymphocytes ratio (NLR) were predictive of a better overall survival (OS) and disease-free survival (DFS). A prognostic score was developed based on DFI and NLR data, identifying 2 risk class groups for DFS (3-years DFS 20.2% for the high-risk group [HRG]and 46.4% for the low-risk group [LRG] [<0.0001]) and 3 risk groups for OS (3 years OS 53.9% for the HRG vs. 76.9% for the intermediate-risk group and 100% of the LRG (p < 0.0001)). The proposed prognostic score effectively predicts outcomes for patients with lung metachronous oligo-metastases from the surgically treated sarcoma.

Preoperative Radiochemotherapy in Rectal Cancer: Is There an Impact of Oxaliplatin on Pathologic Complete Response and Survival Rates under "Real World" Conditions?

This study aimed to evaluate the benefit of additional administration of oxaliplatin during fluorouracil-based neoadjuvant radiochemotherapy (nRCT) in terms of pathologic complete remission (pCR), disease-free survival (DFS), and overall survival (OS) in patients with advanced rectal cancer. Between 2006 and 2021, 669 patients (pts) were diagnosed with locally advanced rectal cancer, of whom a total of 414 pts with nRCT were identified and included in the study. A total of 283 pts were treated by nRCT using concurrent chemotherapy with fluorouracil or capecitabine; 131 pts were treated using a combination of fluorouracil or capecitabine and oxaliplatin. Propensity score matching analyses (PSM) with 114 pts in each group were used to balance the patients' characteristics. OS, DFS, pCR-rate, and potential prognostic factors were compared between the two groups. The median follow-up time was 59.5 weeks in the fluorouracil-group and 43 weeks in the fluorouracil/oxaliplatin group (p = 0.003). After PSM, the pCR-rate (including sustained clinical complete remission) was 27% (31/114 pts) in the fluorouracil/oxaliplatin group and 16% (18/114 pts) in the fluorouracil-group (p = 0.033). There was no difference between these two groups for both 10-year OS and DFS neither before nor after PSM, respectively (OS: 72.6% vs. 55.4%, p = 0.066, and 67.8% vs. 55.1%, p = 0.703, and DFS: 44.8% vs. 46.8%, p = 0.134, and 44.7% vs. 42.3%, p = 0.184). Multivariate analysis identified regression grading according to Dworak grade 4 (HR: 0.659; CI: 0.471-0.921; p = 0.015) and age over 60 years (HR: 2.231; CI: 1.245-4.001; p = 0.007) as independent predictors for OS. In conclusion, the addition of oxaliplatin to fluorouracil during nRCT significantly improved pCR-rate without having an impact on survival.

Omission of axillary lymph node dissection in patients with ypN+ breast cancer after neoadjuvant chemotherapy: A retrospective multicenter study (KROG 21-06)

BackgroundWe evaluated the impact of omitting axillary lymph node dissection (ALND) on oncological outcomes in breast cancer patients with residual nodal disease after neoadjuvant chemotherapy (NAC). MethodsThe medical records of patients who underwent NAC followed by surgical resection and had residual nodal disease were retrospectively reviewed. In total, 1273 patients from 12 institutions were included; all underwent postoperative radiotherapy. Axillary surgery consisted of ALND in 1103 patients (86.6%) and sentinel lymph node biopsy (SLNBx) alone in 170 (13.4%). Univariate and multivariate analyses of disease-free survival (DFS) and overall survival (OS) were performed before and after propensity score matching (PSM). ResultsThe median follow-up was 75.3 months (range, 2.5–182.7). Axillary recurrence rates were 4.8% in the ALND group (n = 53) and 4.7% in the SLNBx group (n = 8). Before PSM, univariate analysis indicated that the 5-year OS rate was inferior in the ALND group compared to the SLNBx group (86.6% vs. 93.3%, respectively; P = 0.002); multivariate analysis did not show a difference between groups (P = 0.325). After PSM, 258 and 136 patients were included in the ALND and SLNBx groups, respectively. There were no significant differences between the ALND and SLNBx groups in DFS (5-year rate, 75.8% vs. 76.9%, respectively; P = 0.406) or OS (5-year rate, 88.7% vs. 93.1%, respectively; P = 0.083). ConclusionsSLNBx alone did not compromise oncological outcomes in patients with residual nodal disease after NAC. The omission of ALND might be a possible option for axillary management in patients treated with NAC and postoperative radiotherapy.

Effect and safety of pegylated recombinant human G-CSF on hematopoietic reconstitution after autologous hematopoietic stem cell transplantation in lymphoma patients

Objective: Efficacy and safety analysis of pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) in promoting hematopoietic recovery after autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with lymphoma. Methods: A total of 149 patients after auto-HSCT in Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were enrolled in this study from April 2016 to December 2021. There were 75 cases in the PEG-rhG-CSF group who were given a single subcutaneous dose of 100 µg/kg on the first day and +8 d, while 74 cases in the rhG-CSF group were given a dose of 5-10 µg·kg(-1)·d(-1) by subcutaneous injection from +1d continuing to an absolute value of neutrophil (ANC) of more than 1.5×10(9)/L. Results: ①The time of grade 3/4 agranulocytosis and neutrophil implantation in the PEG-rhG-CSF group were significantly different from that in rhG-CSF group (P=0.010, 0.030, 0.007) . There were no significant differences in the platelet implantation time, anemia incidence and duration, and platelet and red blood cell infusion within 1 month after transplantation between groups. ②The agranulocytosis with fever incidence in PEG-rhG-CSF group was similar to that in rhG-CSF group (84.0% vs 82.4% , P=0.798) , but the duration was shorter in the PEG-rhG-CSF group (4.0 d vs 5.5 d, P=0.005) . ③The incidence of infection in the PEG-rhG-CSF and the rhG-CSF groups were 22.7% (17/75) and 31.1% (23/74) , respectively (P=0.247) , and the bloodstream infection incidence were 5.3% (4/75) and 9.5% (7/74) , respectively (P=0.336) . ④The PEG-rhG-CSF group and rhG-CSF group's mean length of hospital stay were 31.5 (23-43) days and 37 (25-75) days, respectively (P<0.001) . ⑤The PEG-rhG-CSF group and rhG-CSF group's disease-free survival rates were (96.4±2.5) % and (94.7±2.6) % (P=0.638) , respectively, and the OS rates were 100.0% and (98.6±1.3) % (P=0.312) , respectively. Conclusion: PEG-rhG-CSF application after auto-HSCT in patients with lymphoma can promote hematopoietic granulocyte reconstruction and shorten hospital stay, but has no significant effect on the incidence of infection, disease-free survival, and overall survival after transplantation.

Entire vs. Medial Supraclavicular Nodal Irradiation for Patients with High-Risk Node-Positive Breast Cancer

<h3>Purpose/Objective(s)</h3> We aimed to examine whether elective inclusion of the posterolateral supraclavicular node (SCL) region to the standard medial SCL target volume improves survival outcomes in patients with high-risk node-positive breast cancer undergoing regional nodal irradiation (RNI). <h3>Materials/Methods</h3> We retrospectively reviewed 544 consecutive women with high-risk breast cancer treated with postoperative chest wall/breast and RNI in our center from 1/2015-12/2016. High-risk features were defined as clinical or pathological stage N2-3b disease. Patients were classified into standard medial supraclavicular nodal irradiation (M-SCLI) group and the entire supraclavicular nodal irradiation (E-SCLI) group, which included both the medial and posterolateral SCL region. Disease-free survival (DFS) and overall survival (OS) curves were analyzed by the Kaplan-Meier method and compared using the log-rank test. Propensity-score matching (PSM) and multivariate cox regression analysis were used to evaluate the effect of SCL irradiation target volume on survival outcomes. <h3>Results</h3> The median follow-up time is 64.2 months (range, 6.2-82.6). In the entire cohort, the 5-year DFS rates were 78.5% in the M-SCLI group and 78.8% in the E-SCLI group(P=0.772), and the 5-year OS rates were 92.2% and 90.0% (P=0.210), respectively. Similarly, in the matched cohort, there was no significant difference between the M-SCLI and E-SCLI groups for 5-year DFS (78.2% vs. 77.7%, P=0.892) and OS (92.1% vs. 87.6%, P=0.071). Multivariate analysis demonstrated that E-SCLI was not independently prognostic for DFS (HR 0.80; 95%CI, 0.51 to 1.27; P=0.350) and OS (HR, 1.52; 95%CI, 0.79 to 2.94; P=0.212). The rate of SCL recurrence was low in both groups. <h3>Conclusion</h3> E-SCLI does not appear to be associated with improved DFS and OS in high-risk node-positive breast cancer. This study suggests that M-SCLI should remain standard for most node-positive breast cancer patients (≤N3b disease).

300. RETROSPECTIVE STUDY FOR EVALUATING IMPACT OF NEOADJUVANT THERAPY USING CDDP +5-FU TOWARD ELDERLY ESOPHAGEAL CANCER PATIENTS

Abstract A number of elderly esophageal cancer patients who have eligibility for radical esophagectomy are increasing. However, we have no clearly evidence of treating strategy for these population because mostly high evidential clinical studies doesn’t include over 75-year-old patients. In this study, we retrospectively assessed efficacy of neoadjuvant chemotherapy using CDDP +5-FU in over 75-year-old patient in our hospital. We extracted total 105 over 75-year-old esophageal cancer patients who underwent radical esophagectomy from 2007 to 2020 in our hospital. We classified them Group A (surgery alone) and Group B (neo-FP(±RT) + surgery) and analyzed perioperative surgical risk, surgical outcomes, and adverse events or effectiveness for neoadjuvant therapy. Furthermore, long-term survival was assessed by using matched cohort from propensity score matching. Preoperative risk score calculated by E-pass scoring system was significantly higher in group A while surgical score was similar between two groups. Among group B, 86% of patients were underwent neoadjuvant chemotherapy (NAC) and its completion rate was 78.9%. Number of the patients occurred adverse events during NAC were 8/7/12/3 in the G1/2/3/4 respectively. Postoperative complications decided by Clavien-Dindo classification weren’t seen significant difference between two groups. Postoperative in hospital days were significantly shorter in group A. Survival analysis showed significantly worse overall survival and disease-free survival in group A in both all cohort and matched cohort. The level of preoperative risk score was different between two different treatment strategies. Although this study has several limitations including low number population, difference of preoperative risk, and short follow up period, neoadjuvant therapy using FP may safety and effective treatment for elderly esophageal cancer patients.

Analysis of non-sentinel lymph node status on 10-year overall survival among patients with breast cancer and sentinel lymph node metastasis.

e12584 Background: To investigate retrospectively the effect of non-sentinel lymph node status (non-SLN) on 10-year overall survival (OS) and non-SLN metastasis risk factors in patients with breast cancer and sentinel lymph node (SLN) metastasis. Methods: A large population (n = 15510) underwent SLN dissection in Cancer Hospital, Chinese Academy of Medical Sciences from 2011 to 2022. In total, 3033 (19.6%) cases had at least one SLN metastasis, which underwent axillary lymph node (ALN) dissection. The clinicopathological characteristics and their relationship with non-SLN status were analyzed. Among patients from 2011-2012(n = 132), the effect of non-SLN status on 10-year OS and disease-free survival (DFS) with SLN metastasis were also analyzed. Results: In 3033 patients with SLN metastasis, the mean age was (50.42±10.59) years. The average number of SLN metastasis in each patient was 1.75±1.21, the average number of SLN detected was 4.89±2.03 and the average number of ALN removed was 22.36±8.88. The number of SLN metastasis≥2 and positive lympho-vascular invasion were risk factors of non-SLN metastasis ( P&lt; 0.05), but not the age, T stage and histological grade. In 132 patients from 2011-2012, a median follow-up of 9.1 years (interquartile range, 7.3-9.5 years), the non-SLN metastasis occurred in 60 cases (45.5%), DFS 70.8%, OS 85.9%; non-SLN non-metastasis occurred in 72 cases (54.5%), DFS 85.6%, OS 90.4%. There was no significant difference between two groups in DFS(χ² = 0.61, P = 0.43) and OS (χ² = 0.06, P = 0.81). Conclusions: The number of SLN metastasis≥2 and positive lympho-vascular invasion were risk factors of non-SLN metastasis. There were no significant differences between non-SLN metastasis group and non-metastasis group in DFS and OS.

Clinical Significance of Surgical Resection Timing from Endoscopic Stenting for Left-Sided Large-Bowel Obstruction in Colorectal Cancer.

The optimal interval between self-expanding metallic stent (SEMS) insertion and surgery remains controversial in malignant left-sided large-bowel obstruction (MLLO), especially with respect to oncologic aspects. The aim of this study is to examine whether the time interval to surgery is related to oncologic outcomes. Prospectively collected database of MLLO between January 2005 and December 2017 were reviewed. They were divided according to established cut-off value of 14days for the time interval to surgery. The two groups (early and late groups) were compared with respect to disease-free survival (DFS) and overall survival (OS). Additional subgroup analysis was performed using the established cut-off values for patients with stage II and III tumors. A total of 149 patients underwent surgery after SEMS insertion. There were no significant differences between the early and late groups in the 5-year DFS (78.0% vs 72.4%; P = 0.513) and the OS (74.2% vs 75.7%; P = 0.864) rates in all MLLO. Subgroup analysis showed that there were significant differences between the two groups for DFS and OS in stage II MLLO. The multivariate Cox regression analysis in stage II MLLO demonstrated that the time to surgery was a prognostic factor for DFS (HR, 2.051; 95% CI, 1.528-42.136; P = 0.014) and for OS (HR, 4.947; 95% CI, 1.520-16.107; P = 0.008). The time to surgery was demonstrated not to be a significant prognostic factor in all MLLO. However, it was a prognostic factor for patients with stage II MLLO.

Could Surgery Improve Survival in Patients with Advanced Endometrial Cancer?

Background: Patients with endometrial cancer are mostly diagnosed at an early stage. But unfortunately 10% to 15% of endometrial cancer patients will present with advanced-stage disease, and hence poorer prognosis. When disease is primarily intraperitoneal, cytoreduction to reduced to no visible disease remaining. Aim: Of the work is to detect the survival rate benefits of primary surgery in patients with advanced endometrial cancer at gynecologic oncology unit in El Shatby Maternity University Hospital. Methods and Materials: Retrospective study was conducted on 102 patients diagnosed to have advanced endometrial cancer FIGO (stage III/IV) in a duration of 4 years between 2016 and 2020 and had undergone cytoreductive surgery. The patients were further subdivided into two groups: group 1 who underwent optimal cytoreduction with residual disease less than or equal 1 cm visible lesion, and group 2 who had residual disease more than 1 cm visible lesion and they were followed to check the survival benefits. Results: The mean of disease free survival in group: 1) patients was 2 years which was significantly longer than those in group; 2) those who had residual disease > 1 cm, p I endometrial cancer had significantly longer (DFS) than those diagnosed to have type II endometrial cancer, p = 0.046. Conclusion: Primary complete cytoreductive (upfront) surgery when possible has a favorable impact on overall survival in patients with advanced endometrial cancer.

The Use of Machine Learning to Create a Risk Score to Predict Survival in Patients with Hepatocellular Carcinoma: A TCGA Cohort Analysis.

Introduction Hepatocellular carcinoma (HCC) accounts for approximately 90% of primary liver malignancies and is currently the fourth most common cause of cancer-related death worldwide. Due to varying underlying etiologies, the prognosis of HCC differs greatly among patients. It is important to develop ways to help stratify patients upon initial diagnosis to provide optimal treatment modalities and follow-up plans. The current study uses Artificial Neural Network (ANN) and Classification Tree Analysis (CTA) to create a gene signature score that can help predict survival in patients with HCC. Methods The Cancer Genome Atlas (TCGA-LIHC) was analyzed for differentially expressed genes. Clinicopathological data were obtained from cBioPortal. ANN analysis of the 75 most significant genes predicting disease-free survival (DFS) was performed. Next, CTA results were used for creation of the scoring system. Cox regression was performed to identify the prognostic value of the scoring system. Results 363 patients diagnosed with HCC were analyzed in this study. ANN provided 15 genes with normalized importance >50%. CTA resulted in a set of three genes (NRM, STAG3, and SNHG20). Patients were then divided in to 4 groups based on the CTA tree cutoff values. The Kaplan–Meier analysis showed significantly reduced DFS in groups 1, 2, and 3 (median DFS: 29.7 months, 16.1 months, and 11.7 months, p < 0.01) compared to group 0 (median not reached). Similar results were observed when overall survival (OS) was analyzed. On multivariate Cox regression, higher scores were associated with significantly shorter DFS (1 point: HR 2.57 (1.38–4.80), 2 points: 3.91 (2.11–7.24), and 3 points: 5.09 (2.70–9.58), p < 0.01). Conclusion Long-term outcomes of patients with HCC can be predicted using a simplified scoring system based on tumor mRNA gene expression levels. This tool could assist clinicians and researchers in identifying patients at increased risks for recurrence to tailor specific treatment and follow-up strategies for individual patients.

A Combined Nomogram Model to Predict Disease-free Survival in Triple-Negative Breast Cancer Patients With Neoadjuvant Chemotherapy.

Background: To investigate whether the radiomics signature (Rad-score) of DCE-MRI images obtained in triple-negative breast cancer (TNBC) patients before neoadjuvant chemotherapy (NAC) is associated with disease-free survival (DFS). Develop and validate an intuitive nomogram based on radiomics signatures, MRI findings, and clinicopathological variables to predict DFS. Methods: Patients (n = 150) from two hospitals who received NAC from August 2011 to May 2017 were diagnosed with TNBC by pathological biopsy, and follow-up through May 2020 was retrospectively analysed. Patients from one hospital (n = 109) were used as the training group, and patients from the other hospital (n = 41) were used as the validation group. ROIs were drawn on 1.5 T MRI T1W enhancement images of the whole volume of the tumour obtained with a 3D slicer. Radiomics signatures predicting DFS were identified, optimal cut-off value for Rad-score was determined, and the associations between DFS and radiomics signatures, MRI findings, and clinicopathological variables were analysed. A nomogram was developed and validated for individualized DFS estimation. Results: The median follow-up time was 53.5 months, and 45 of 150 (30.0%) patients experienced recurrence and metastasis. The optimum cut-off value of the Rad-score was 0.2528, which stratified patients into high- and low-risk groups for DFS in the training group (p<0.001) and was validated in the external validation group. Multivariate analysis identified three independent indicators: multifocal/centric disease status, pCR status, and Rad-score. A nomogram based on these factors showed discriminatory ability, the C-index of the model was 0.834 (95% CI, 0.761–0.907) and 0.868 (95% CI, 0.787–949) in the training and the validation groups, respectively, which is better than clinicoradiological nomogram(training group: C-index = 0.726, 95% CI = 0.709–0.743; validation group: C-index = 0.774,95% CI = 0.743–0.805). Conclusion: The Rad-score derived from preoperative MRI features is an independent biomarker for DFS prediction in patients with TNBC to NAC, and the combined radiomics nomogram improved individualized DFS estimation.

Laparoscopic versus open resection for rectal cancer: An individual patient data meta analysis of randomized controlled trials

Background and aimsThe role of laparoscopic rectal cancer resection remains controversial. Thus, we aimed to conduct a one-stage meta-analysis with reconstructed patient-level data using randomized trial data to compare long-term oncologic efficacy of laparoscopic and open surgical resection for rectal cancer. MethodsMedline, EMBASE and Scopus were searched for articles comparing laparoscopic with open surgery for rectal cancer. Primary outcome was disease free survival (DFS) while secondary outcome was overall survival (OS). One-stage meta-analysis was conducted using patient-level survival data reconstructed from Kaplan-Meier curves with Web Plot Digitizer. Shared-frailty and stratified Cox models were fitted to compare survival endpoints. ResultsSeven randomized trials involving 1767 laparoscopic and 1293 open resections for rectal cancer were included. There were no significant differences between both groups for DFS and OS with respective hazard ratio estimates of 0.91 (95% CI: 0.78–1.06, p = 0.241) and 0.86 (95% CI:0.73–1.02, p = 0.090). Sensitivity analysis for non-metastatic patients and patients with mid and lower rectal cancer showed no significant differences in OS and DFS between both surgical approaches. In the laparoscopic arm, improved DFS was noted for stage II (HR: 0.73, 95% CI:0.54–0.98, p = 0.036) and stage III rectal cancers (HR: 0.74, 95% CI:0.55–0.99, p = 0.041). ConclusionsThis meta-analysis concludes that laparoscopic rectal cancer resection does not compromise long-term oncologic outcomes compared with open surgery with potential survival benefits for a minimal access approach in patients with stage II and III rectal cancer.

Long-term oncologic outcomes of transanal TME compared with transabdominal TME for rectal cancer: a systematic review and meta-analysis

BackgroundTransanal total mesorectal excision (TaTME) appears to have favorable surgical and pathological outcomes. However, the evidence on survival outcomes remains unclear. We performed a meta-analysis to compare long-term oncologic outcomes of TaTME with transabdominal TME for rectal cancer.MethodsPubMed, EMBASE, and the Cochrane Library were searched. Data were pooled, and overall effect size was calculated using random-effects models. Outcome measures were overall survival (OS), disease-free survival (DFS), and local and distant recurrence.ResultsWe included 11 nonrandomized studies that examined 2,143 patients for the meta-analysis. There were no significant differences between the two groups in OS, DFS, and local and distant recurrence with a RR of 0.65 (95% CI 0.39–1.09, I2 = 0%), 0.79 (95% CI 0.57–1.10, I2 = 0%), 1.14 (95% CI 0.44–2.91, I2 = 66%), and 0.75 (95% CI 0.40–1.41, I2 = 0%), respectively.ConclusionIn terms of long-term oncologic outcomes, TaTME may be an alternative to transabdominal TME in patients with rectal cancer. Well-designed randomized trials are warranted to further verify these results.

Laparoscopic Versus Open Resection for Rectal Cancer: A Meta-Analysis of Reconstructed Individual Data on 3060 Patients Treated in Randomized Controlled Trials

Background and Aims: The role of laparoscopic rectal cancer resection remains controversial. Previous meta-analyses of survival outcomes have utilized a standard meta-analytical approach less amenable to the incorporation of flexible and robust survival models. Thus, we aimed to conduct a one-stage meta-analysis with reconstructed patient-level data using randomized trial data to compare long-term oncologic efficacy of laparoscopic and open surgical resection for rectal cancer. Methods: Medline, EMBASE and Scopus were searched for articles comparing laparoscopic with open surgery for rectal cancer. Primary outcome was disease free survival (DFS) while secondary outcome was overall survival (OS). One-stage meta-analysis was conducted using patient-level survival data reconstructed from Kaplan-Meier curves with Web Plot Digitizer. Shared-frailty and stratified Cox models were fitted to compare survival endpoints. Results: Seven randomized trials, with a median follow-up of six years, involving 1,767 laparoscopic and 1,293 open resections for rectal cancer in 3,060 patients were included. There were no significant differences between both groups for DFS and OS with respective hazard ratio estimates of 0.91 (95% CI: 0.78 – 1.06, p =0.241) and 0.86 (95% CI: 0.73 - 1.02, p = 0.090). Sensitivity analysis for non-metastatic patients and patients with mid and lower rectal cancer showed no significant differences in OS and DFS between both surgical approaches. In the laparoscopic arm, improved DFS was noted for stage II (HR: 0.73, 95% CI: 0.54 - 0.98, p = 0.036) and stage III rectal cancers (HR: 0.74, 95% CI: 0.55 - 0.99, p =0.041). Conclusions: This meta-analysis concludes that laparoscopic rectal cancer resection does not compromise long-term oncologic outcomes compared with open surgery with potential survival benefits for a minimal access approach in patients with stage II and III rectal cancer. Funding: No funding was required for this work. Declaration of Interest: None to declare.

Using Genomics Feature Selection Method in Radiomics Pipeline Improves Prognostication Performance in Locally Advanced Esophageal Squamous Cell Carcinoma-A Pilot Study.

Simple SummaryPrognosis for patients with locally advanced esophageal squamous cell carcinoma (ESCC) remains poor mainly due to late diagnosis and limited curative treatment options. Neoadjuvant chemoradiotherapy (nCRT) plus surgery is considered the standard of care for patients with locally advanced ESCC. Currently, predicting prognosis remains a challenging task. Quantitative imaging radiomics analysis has shown promising results, but these methods are traditionally data-intensive, requiring a large sample size, and are not necessarily based on the underlying biology. Feature selection based on genomics is proposed in this work, leveraging differentially expressed genes to reduce the number of radiomic features allowing for the creation of a CT-based radiomic model using the genomics-based feature selection method. The established radiomic signature was prognostic for patients’ long-term survival. The radiomic nomogram could provide a valuable prediction for individualized long-term survival.Purpose: To evaluate the prognostic value of baseline and restaging CT-based radiomics with features associated with gene expression in esophageal squamous cell carcinoma (ESCC) patients receiving neoadjuvant chemoradiation (nCRT) plus surgery. Methods: We enrolled 106 ESCC patients receiving nCRT from two institutions. Gene expression profiles of 28 patients in the training set were used to detect differentially expressed (DE) genes between patients with and without relapse. Radiomic features that were correlated to DE genes were selected, followed by additional machine learning selection. A radiomic nomogram for disease-free survival (DFS) prediction incorporating the radiomic signature and prognostic clinical characteristics was established for DFS estimation and validated. Results: The radiomic signature with DE genes feature selection achieved better performance for DFS prediction than without. The nomogram incorporating the radiomic signature and lymph nodal status significantly stratified patients into high and low-risk groups for DFS (p < 0.001). The areas under the curve (AUCs) for predicting 5-year DFS were 0.912 in the training set, 0.852 in the internal test set, 0.769 in the external test set. Conclusions: Genomics association was useful for radiomic feature selection. The established radiomic signature was prognostic for DFS. The radiomic nomogram could provide a valuable prediction for individualized long-term survival.

Simultaneous surgery for synchronous liver metastases of colorectal cancer: analysis of survival and negative prognosis factors

Aim. To improve the surgical treatment results among patients with synchronous liver metastasis of colorectal cancer. Materials and methods. From 2012 to 2019, the analysis of the results of treatment of 60 patients with colorectal cancer and synchronous metastatic liver disease was carried out. The study sample was divided into 2 groups of patients. The group 1 consisted of 30 patients who got simultaneous resection of liver metastases and primary colorectal cancer. The group 2 consisted of other 30 patients who got stage resections: surgery for the primary tumor at the first stage, and liver surgery for metastases at the second.Results. The median operative time was 340 ± 21.1 minutes in the group 1. In the group 2 it was 255 ± 21.1 minutes and only the liver resection stage was assessed. The median blood loss in patients of the group 1 was 520,0 [200,0;800,1] ml, in the group 2 it was 500,0 [175,0;1300,0] ml. In general, we identified 5 cases of complications. In the postoperative period, 4 patients died. The average follow-up period is 23 months. One-year survival in group 1 was 92.6%, in group 2 – 100%, three-year – 85.2% and 89.6%. One-year disease-free survival in group 1 is 70%, in group 2 – 83.3%, three-year disease-free survival – 43.3% and 36.7%.Overall and disease-free survival rates didn’t differ significantly between the two treatment strategies. We detected significant effect on the disease-free and overall survival of regional lymph nodes metastasis (both p &lt; 0.05).Conclusion. The long-term and immediate results of simultaneous surgery of synchronous liver metastasis of colorectal cancer are comparable to the results of the staged method of treatment. It indicates the safety and effectiveness of simultaneous procedure.

A propensity score-matched comparison of recurrence outcomes after immediate implant vs autologous flap reconstruction in patients receiving neoadjuvant chemotherapy for breast cancer.

We compared oncologic outcomes between breast cancer patients who underwent immediate implant-based breast reconstruction (IBBR) and those who underwent autologous flap reconstruction (AFR) after neoadjuvant chemotherapy (NACT). The study group comprised 536 patients with primary breast cancer who underwent NACT followed by immediate IBBR or AFR. After propensity score matching, 138 patients in the IBBR group and 276 patients in the AFR group were selected for comparisons of locoregional recurrence-free survival (LRRFS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and breast cancer-specific survival (BCSS). No significant differences were observed between the matched groups in locoregional recurrence rates (IBBR vs. AFR: 12.3% vs. 12%; P = 0.915) and distant metastasis (13% vs. 17%; P = 0.293). There was also no significant difference between the groups in LRRFS (P = 0.956), DFS (P = 0.606), DMFS (P = 0.283), or BCSS (P = 0.121). The 5- and 10-year LRRFS rates were 87.6% and 85.9% in the IBBR group, and 87.7% and 86.1% in the AFR group; the 5- and 10-year DFS rates were 79% and 77.5% in the IBBR group, and 77% and 75% in the AFR group; the 5- and 10-year DMFS rates were 85.9% and 85.9% in the IBBR group, and 83.2% and 81.8% in the AFR group; and the 5- and 10-year BCSS rates were 97.8% and 91.3% in the IBBR group, and 91.8% and 86% in the AFR group, respectively. In this propensity score-matched analysis of oncologic outcomes in breast cancer patients who underwent immediate reconstruction after NACT, no significant differences were observed between the IBBR and AFR groups.