Favorable Factor For Overall Survival Research Articles

Results of Stereotactic Body Radiotherapy With CyberKnife-M6 for Primary and Metastatic Lung Cancer.

The aim of the study was to evaluate the efficacy of stereotactic body radiotherapy (SBRT) using the CyberKnife-M6 (CK-M6) with lung optimized treatment (LOT) module in patients with primary lung cancer and lung metastases. Forty-two lesions from 35 patients were treated between 2019 and 2022. Four-dimensional computed tomography images were obtained when the patients were in a free breathing modality. Tracking modality was selected prospectively according to the visibility of the target. The median prescribed dose was 48 Gy in four fractions (fx) (28 - 55 Gy/1- 7 fx). The median age was 68 years (47 - 82 years), and 43% of cases were adenocarcinoma. The median lesion size was 15 mm (6 - 36 mm). Complete, partial and stable responses were obtained as 26%, 62%, and 9.5% at a median of 2 months (1 - 6 months), and 35.5%, 47.5% and 5% at the 12th month evaluation, respectively. Grade 3 and higher toxicity was not observed in any case. The mean and 2-year overall survival (OS) was 31.5 months and 54%, and the local recurrence-free survival (LRFS) was 29.6 months and 51%, respectively. In univariate analysis, target lesion type, complete response (CR), and higher esophagus maximum dose were favorable factors for OS and LRFS (P < 0.05). The CR at 12th month evaluation remained significant in multivariate analysis in terms of OS (hazard ratio = 8.602, 95% confidence interval: 1.05 - 70.01; P = 0.044). A mean LRFS of 29.6 months and OS of 31.5 months were obtained in patients with primary and metastatic lung cancer. With a median treatment time of 25 min, motion-managed strategy with CK-M6-LOT-based SBRT is an effective, safe, and comfortable treatment method for lung cancer.

Prognostic factors in 448 newly diagnosed multiple myeloma receiving bortezomib-based induction: impact of ASCT, transplant refusal and high-risk MM

In Hong Kong, newly diagnosed multiple myeloma (NDMM) receives bortezomib-based triplet induction. Upfront autologous stem cell transplant (ASCT) is offered to transplant eligible (TE) patients (NDMM ≤ 65 years of age), unless medically unfit (TE-unfit) or refused (TE-refused). Data was retrieved for 448 patients to assess outcomes. For the entire cohort, multivariate analysis showed that male gender (p = 0.006), international staging system (ISS) 3 (p = 0.003), high lactate dehydrogenase (LDH) (p = 7.6 × 10−7) were adverse predictors for overall survival (OS), while complete response/ near complete response (CR/nCR) post-induction (p = 2.7 × 10−5) and ASCT (p = 4.8 × 10−4) were favorable factors for OS. In TE group, upfront ASCT was conducted in 252 (76.1%). Failure to undergo ASCT in TE patients rendered an inferior OS (TE-unfit p = 1.06 × 10−8, TE-refused p = 0.002) and event free survival (EFS) (TE-unfit p = 0.00013, TE-refused p = 0.002). Among TE patients with ASCT, multivariate analysis showed that age ≥ 60 (p = 8.9 × 10−4), ISS 3 (p = 0.019) and high LDH (p = 2.6 × 10−4) were adverse factors for OS. In those with high-risk features (HR cytogenetics, ISS 3, R-ISS 3), ASCT appeared to mitigate their adverse impact. Our data reaffirmed the importance of ASCT. The poor survival inherent with refusal of ASCT should be recognized by clinicians. Finally, improved outcome with ASCT in those with high-risk features warrant further studies.

Comparison of Hematopoietic Stem Cell Transplantation and Repeated Immunosuppressive Therapy As Second-Line Treatment for Relapsed/Refractory Severe Aplastic Anemia

The optimal treatment for patients with severe aplastic anemia (SAA) who fail or have relapse after an initial course of immunosuppressive therapy (IST) has not been established. We conducted a retrospective study to compare the effectiveness of allogeneic hematopoietic stem cell transplantation (allo-HSCT) (n = 36) with repeated IST (n = 33) as salvage therapy for relapsed/refractory SAA between 2007 and 2022. In the repeated IST group, patients were treated with antithymocyte globulin (ATG) (n = 16) or high-dose cyclophosphamide (HD-CTX) (n = 17). The overall response rate was 42.4% at 6 months, and 60.6% at 12 months. In the HSCT group, 6 were matched sibling donor (MSD), 7 were matched unrelated donor (MUD), and 23 were haploidentical donor (HID). All patients achieved neutrophil engraftment and no primary graft failure was observed. The rate of platelet engraftment was 88.9%, with a median time of 16 days. The cumulative incidences of grade II-IV, III-IV acute GVHD was 36.1% ± 0.7%, 13.9% ± 0.3% at day +100, and chronic GVHD was 36.2% ± 0.7% at 5 years. Compared with IST, HSCT recipients showed much higher hematologic recovery rate at 3-, 6- and 12-months post treatment (63.9%, 83.3% and 86.1%, respectively, P &amp;lt; 0.001). The estimated 5-year overall survival (OS) (79.8% ± 6.8% vs. 80.0% ± 7.3%, p = 0.957) were similar; however, the estimated 5-year failure-free survival (FFS) was significantly better in the HSCT group (79.8% ± 6.8% vs. 55.2% ± 9.2%, p = 0.049). In multivariate analysis, age ≤ 35 years at salvage HSCT was the only favorable factor for OS and FFS ( p = 0.019, 95% CI 0.019-0.706). These results suggest that HSCT and repeated IST are both effective for refractory/relapsed SAA in the salvage setting. Considering the superior FFS in the HSCT cohort, especially in younger patients (age ≤ 35 years), we recommend HSCT instead of a second IST for these patients.

The efficacy of radical hepatectomy versus stereotactic body radiotherapy for primary hepatocellular carcinoma: A propensity score matching analysis.

4130 Background: Recent international guidelines have included stereotactic body radiotherapy (SBRT) which outstanding tumor control as a treatment option for hepatocellular carcinoma (HCC) in several settings. However, data evaluating surgery and SBRT are limited, and results published were controversial. The retrospective study aims to compare the efficacy of hepatectomy and SBRT for HCC. Methods: The study population started with patients in databases of primary HCC, treated with curative hepatectomy or SBRT, regardless of tumor number, tumor size, cirrhosis and portal vein thrombosis. Patients with prior cancer treatment other than transarterial chemoembolization were excluded. In order to reduce the potential confounding effect of treatment and selection bias, 3-to-1 propensity score models were constructed based on each patient’s estimated propensity score. The variables significant for overall survival were considered for the match, including age, sex, Child-Pugh score, ECOG performance status score, maximum diameter, BCLC stage, prothrombin time, total bilirubin, albumin, and white blood cell. Overall survival and progression-free survival were compared. Results: A total of 174 patients, 154 in hepatectomy group and 20 in SBRT group, were analyzed. 125 men and 29 women, mean 56.2 years of age, in hepatectomy group. 12 men and 8 women, mean 70.5 years of age, in SBRT group. ECOG was a significant favorable factor for overall survival. Maximum diameter, portal vein embolization, aspartate transferase and albumin was significant favorable factors for disease-free survival of patients with primary hepatocellular carcinomas. Before PSM, patients in the hepatectomy group tended to be younger, had better performance status, less cirrhosis, less tumor number and had better hepatic function than those in the SBRT group ( P &lt; .05). The 3-year overall survival rate and median progression-free survival time for the surgical resection and SBRT groups were 77.9% vs 35.4 (P = .003) and 30 vs 20 month (P = .486), respectively. After PSM, 80 patients, 60 in hepatectomy group and 20 in SBRT group, were analyzed. The 3-year overall survival rate and median progression-free survival time for the surgical resection and SBRT groups were 71.9% vs 56.6 (P = .92) and 17 vs 26 month (P = .656), respectively. The patients of hepatectomy group had less cirrhosis, better liver function and less tumor number than those in 20 with SBRT. Conclusions: For primary HCC, regardless of tumor size and tumor number, stereotactic body radiotherapy can provide similar result on overall survival and tumor control compared to hepatectomy. Stereotactic body radiotherapy can also be less invasive and provide less inpatient time. So stereotactic body radiotherapy can be a effective treatment for patients with primary HCC.

High intramuscular adipose tissue content was a favorable prognostic factor in patients with advanced gastric cancer treated with nivolumab monotherapy.

Nivolumab extends the overall survival (OS) of patients with advanced gastric cancer (AGC). Intramuscular adipose tissue (IMAT) is associated with the prognosis of patients with various cancers. We investigated the effect of IMAT on OS in patients with AGC treated with nivolumab. We enrolled patients with AGC treated with nivolumab (n=58, 67years old, men/women 40/18). The subjects were classified into long-term or short-term survival groups according to the median value. The IMAT was evaluated using computed tomography scans at the umbilical level. The decision tree algorithm was employed to reveal the profile associated with prognosis. In decision tree analysis, immune-related adverse events (irAEs) were the first divergence variable, and prolonged survival was observed in 100% of patients with irAEs (profile 1). However, long survival was observed in 38% of patients with no irAEs. Among these patients, IMAT was identified as the second divergence variable, and long survival was observed in 63% of patients with high IMAT (profile 2). In patients with low IMAT, only 21% showed prolonged survival (profile 3). Median OS was 717days (95% confidence interval [CI], 223 to not reached) in profile 1, 245days (95% CI, 126 to 252) in profile 2, and 132days (95% CI, 69 to 163) in profile 3. Immune-related adverse events and high IMAT were favorable factors for OS in patients with AGC treated with nivolumab. Thus, along with irAEs, skeletal muscle quality is important in managing patients with AGC treated with nivolumab.

Clinical Study of Cytomegalovirus Infection after Allogeneic Hematopoietic Stem Cell Transplantation

To explore the risk factors of cytomegalovirus (CMV) and refractory CMV infection (RCI) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and their influences on survival. A total of 246 patients who received allo-HSCT from 2015 to 2020 were divided into CMV group (n=67) and non-CMV group (n=179) according to whether they had CMV infection. Patients with CMV infection were further divided into RCI group (n=18) and non-RCI group (n=49) according to whether they had RCI. The risk factors of CMV infection and RCI were analyzed, and the diagnostic significance of Logistics regression model was verified by ROC curve. The differences of overall survival (OS) and progression-free survival (PFS) between groups and the risk factors affecting OS were analyzed. For patients with CMV infection, the median time of the first CMV infection was 48(7-183) days after allo-HSCT, and the median duration was 21 (7-158) days. Older age, EB viremia and gradeⅡ-Ⅳacute graft-versus-host disease (aGVHD) significantly increased the risk of CMV infection (P=0.032, <0.001 and 0.037, respectively). Risk factors for RCI were EB viremia and the peak value of CMV-DNA at diagnosis≥1×104 copies/ml (P=0.039 and 0.006, respectively). White blood cell (WBC)≥4×109/L at 14 days after transplantation was a protective factor for CMV infection and RCI (P=0.013 and 0.014, respectively). The OS rate in CMV group was significantly lower than that in non-CMV group (P=0.033), and also significantly lower in RCI group than that in non-RCI group (P=0.043). Hematopoietic reconstruction was a favorable factor for OS (P<0.001), whereas CMV-DNA≥1.0×104 copies/ml within 60 days after transplantation was a risk factor for OS (P=0.005). The late recovery of WBC and the combination of EB viremia after transplantation are common risk factors for CMV infection and RCI. CMV-DNA load of 1×104 copies/ml is an important threshold, higher than which is associated with higher RCI and lower OS risk.

Circulating HPV16 DNA in Blood Plasma as Prognosticator and Early Indicator of Cancer Recurrence in Radio-Chemotherapy for Anal Cancer.

Implementation of anal squamous cell carcinoma (ASCC) treatment modifications requires reliable patient risk stratification. The circulating tumor-related human papillomavirus type 16 (ctHPV16) may play a role in predicting survival or assessing treatment response. The study included 62 ASCC patients treated with chemoradiotherapy. A threshold of 2.5 was used to determine the maximum standardized uptake value (SUVmax). The ctHPV16 viral load (VL) was quantified by qPCR. In the multivariate Cox analysis, lower SUVmax (p = 0.047) and ctHPV16-positive (p = 0.054) proved to be independent prognostic factors for favorable overall survival (OS). In the subgroup with the higher SUVmax, ctHPV16 and nodal (N) status were independent prognostic factors with p = 0.022 for ctHPV16 and p = 0.053 for N. The best survival rate (95%) presented ctHPV16-positive/N-negative patients. High ctHPV16 VL tended to be slightly specific for patients younger than 63 years (p = 0.152). The decrease in ctHPV16 VL to undetectable level after the end of treatment correlated with the overall clinical response. A prognostic stratification by SUVmax, ctHPV16 and N-positive status allows consideration of more aggressive treatment in high-risk patients (those with high SUVmax, ctHPV16-negative, and N-positive) or de-intensification of therapy in low-risk patients (those with low SUVmax, ctHPV16-positive and N-negative). However, prospective clinical trials on a large group are needed.

Atezolizumab Monotherapy for Non-small Cell Lung Cancer Patients: An Observational Study in Ibaraki Group (ATTENTION-IBARAKI).

Atezolizumab is a monoclonal antibody that targets programmed death-ligand 1 (PD-L1) expressed on cancer cells derived from various organs and antigen-presenting cells and is currently commonly used in combination with chemotherapy. We conducted a study to clarify the current status of response to atezolizumab monotherapy in clinical practice and clarify the factors that contribute to long-term response and survival. We conducted a retrospective review of patients with advanced non-small cell lung cancer (NSCLC) treated with atezolizumab monotherapy from April 2018 to March 2023 at 11 Hospitals. The 147 patients evaluated had a progression-free survival (PFS) of 3.0 months and an overall survival of 7.0 months. Immune-related adverse events of any grade were observed in 13 patients (8.8%), grade 3 or higher in nine patients (6.1%), and grade 5 with pulmonary toxicity in one patient (0.7%). Favorable factors related to PFS were 'types of NSCLC other than adenocarcinoma'. Favorable factors for overall survival were 'performance status 0-1' and 'treatment lines up to 3'. There were 16 patients (10.9%) with PFS >1 year. No characteristic clinical findings were found in these 16 patients compared to the remaining 131 patients. Efficacy and immune-related adverse events of NSCLC patients associated with atezolizumab monotherapy were comparable to those of previous clinical trial results. Knowledge of characteristics of patients who are most likely to benefit from atezolizumab monotherapy is a crucial step towards implementing appropriate prescribing.

Laparoscopic isolated liver segmentectomy 8 for malignant tumors: techniques and comparison of surgical results with the open approach using a propensity score-matched study.

Anatomic isolated liver segmentectomy 8 (ILSeg8) for malignancies remains technically challenging. The feasibility, safety, and oncologic validity of laparoscopic ILSeg8 are undefined, and thus were evaluated in comparison with the open approach. This study enrolled 35 open and 29 laparoscopic ILSeg8 cases of hepatocellular carcinoma (n = 47), metastatic liver tumors (n = 16), and intrahepatic cholangiocarcinoma (n = 1) at our institution. The surgical techniques were based on the pre-hepatectomy extrahepatic Glissonian pedicle control, followed by cranial-to-caudal parenchymal dissection from the hepatic vein root side. The short- and long-term outcomes after ILSeg8 were retrospectively evaluated and compared between the open and laparoscopic approaches using 1:1 propensity score matching (PSM). Both before and after PSM, the laparoscopic ILSeg8 group had significantly less blood loss, lower postoperative serum bilirubin level, and a shorter postoperative hospital stay than the open group. The overall survival rates were comparable between the laparoscopic and open groups before (P = 0.017) and after (P = 0.043) PSM, with the similar recurrence-free survival rates between the groups. In a multivariable analysis of the cohort before PSM (n = 64), the laparoscopic approach was identified to be an independent factor for favorable overall survival (hazard ratio = 0.20, P = 0.039). Laparoscopic ILSeg8 using the extrahepatic Glissonian approach and hepatic vein root at first parenchymal dissection was feasible, safe, and oncologically acceptable. In ILSeg8 for malignancy, the laparoscopic approach potentially confers short-term advantages over the open approach with comparable long-term outcomes in select patients.

Severe aplastic anemia patients with infection who received an allogeneic hematopoietic stem cell transplantation had a better chance: Long-term outcomes of a multicenter study.

Background and aimsHow to select the treatment is a challenge for the management of acquired patients with infections. This study aimed at comparing the outcomes of SAA with infections who had an allogeneic hematopoietic stem cell transplantation (allo-HSCT)with that of patients who had an infection and received non-HSCT therapy.MethodsWe retrospectively compared the outcomes of patients with acquired SAA and infections who had an allo-HSCT (n = 141) with that of patients who had an infection and received non-HSCT therapy (n = 186) between July 2004 and January 2020.ResultsThe treatment-related mortality (TRM) of grade 1-2 infections in the HSCT and non-HSCT groups was 24.99% and 13.68%, respectively (P = 0.206), while the TRM of grade 3-4 infections was lower in the HSCT group than that observed in the non-HSCT group (18.54% vs. 33.33%, P = 0.036). At 6 months post-treatment, 91.30% patients in the HSCT group and 8.78% patients in the non-HSCT group had achieved a normal blood profile (P < 0.0001). The time required to discontinue transfusions of red blood cells and platelets in the non-HSCT group was longer than in the HSCT group (P < 0.0001). Estimated overall survival (OS) at 6 years was similar in the two groups (75.5% ± 3.9% vs. 76.3% ± 3.1%, P = 0.996), while the estimated failure-free survival (FFS) at 6 years was 75.2% ± 3.8% in the HSCT group and 48.9% ± 3.7% in the non-HSCT group (P < 0.0001). Multivariate analysis showed that younger age, lower grade of infection (grade 1-2), and SAA (vs. very SAA) were favorable factors for OS (P < 0.05), and that the choice of HSCT and younger age were favorable factors for FFS (P < 0.0001).ConclusionThese results suggest that allo-HSCT has a better chance of a successful outcome than non-HSCT in SAA patients with an infection.

Tumor-infiltrating neutrophils and peripheral neutrophil-to-lymphocyte ratio conversely predicted the prognosis of patients with non-small cell lung cancer

Increasing evidence indicates that neutrophil-associated prognostic markers, such as, tumor-associated neutrophils (TANs), neutrophil-to-T cell ratio (NTR) and neutrophil-to-lymphocyte ratio (NLR), are strongly correlated with the survival of patients with non-small cell lung cancer (NSCLC). However, either the association or the difference in their predictive efficacies remains unknown. To this aim, we investigated the influence of intratumoural TANs and peripheral NLR on the clinical outcome of NSCLC patients using tumor tissues, peripheral blood indexes, and clinicopathological data of 133 patients diagnosed with NSCLC. Additionally, Kendall correlation analysis was performed to identify the association between TANs and NLR. Our results revealed that intratumoural TANs were effective prognostic factors for favorable overall survival (OS), but were not associated with disease-free survival (DFS) in the subgroup analysis of 84 postoperative patients and progression-free survival (PFS) in 49 non-resectable NSCLC patients. Elevated NTR also indicated favorable prognosis, with high intratumoural NTR being correlated with prolonged OS and high stromal NTR being correlated with prolonged DFS. In contrast, peripheral NLR predicted dismal OS and DFS of patients receiving curative surgery. Furthermore, neither intratumoural nor stromal TANs were found to be associated with NLR, indicating that they were independent inflammatory indexes in predicting the prognosis of NSCLC. In conclusion, we discovered that TANs and NLR independently and oppositely predicted the clinical outcome of NSCLC patients, providing new sights on the role of neutrophil in tumor biology and survival prediction.

Favorable Outcome with Conditioning Regimen of Flu/Bu4/Mel in Acute Myeloid Leukemia Patients in Remission Undergoing Cord Blood Transplantation

Cord blood transplantation (CBT) is a curative therapeutic option for patients with acute myeloid leukemia (AML) who do not have an HLA-matched donor. The decline in early nonrelapse mortality (NRM) after CBT has significantly improved overall survival (OS) during the past 20 years because of advances in CBT practices, including more careful patient selection, use of safer conditioning regimens, better cord blood unit selection, and improved supportive care. A previous study reported a conditioning regimen comprising fludarabine, busulfan, and melphalan (Flu/Bu4/Mel) developed for patients undergoing CBT in non-complete remission (CR) myeloid malignancies that showed durable engraftment and remission with acceptable nonrelapse mortality (NRM), leading to excellent survival outcomes. However, no prior study has focused on the role of Flu/Bu4/Mel in CBT conditioning and compared it with conventional myeloablative conditioning (MAC) for AML patients in CR. We aimed to investigate the efficacy and safety of Flu/Bu4/Mel compared with cyclophosphamide and total body irradiation (CY/TBI)-based MAC for AML patients in CR who underwent CBT. Patients were selected from the Japanese nationwide transplantation registry according to the following inclusion criteria: (1) patients with AML aged ≥16 years, (2) first single-unit CBT, and (3) CR at the time of transplantation. Of 477 eligible patients, 148 (31.0%) received CY/TBI, 223 (46.8%) received high-dose cytarabine (HDCA)/CY/TBI, and 106 (22.2%) received Flu/Bu4/Mel. The probability of OS at 3 years was 64.8% (95% confidence interval [CI], 56.0% to 72.3%) in the CY/TBI group, 65.1% (95% CI, 57.8% to 71.4%) in the HDCA/CY/TBI group, and 65.5% (95% CI, 53.7% to 74.9%) in the Flu/Bu4/Mel group (P=.71); the cumulative incidence of relapse at 3 years was 22.0% (95% CI, 15.2% to 29.5%), 17.2% (95% CI, 12.2% to 22.9%), and 18.0% (95% CI, 11.2% to 26.2%), respectively (P=.40); and the cumulative incidence of NRM at 3 years was 17.2% (95% CI, 11.5% to 24.0%), 20.7% (95% CI, 15.4% to 26.7%), and 18.6% (95% CI, 11.4% to 27.2%), respectively (P=.95). Multivariate analysis identified Flu/Bu4/Mel as a favorable factor for OS; however, it was not significantly favorable for relapse and NRM in the CY/TBI, HDCA/CY/TBI, and Flu/Bu4/Mel groups (hazard ratio [HR], .50 [95% CI, .29-.88], P=.015; .67 [95% CI, .31-1.46], P=.31; and .55 [95% CI, .26-1.18], respectively; P=.12). Flu/Bu4/Mel was a favorable factor for neutrophil engraftment (HR, 1.51; 95% CI, 1.08 to 2.12; P=.016). Multivariate analysis showed that Flu/Bu4/Mel had a favorable prognostic impact on OS and neutrophil engraftment despite the non-TBI regimen. Our findings suggest that Flu/Bu4/Mel may sustain the antileukemia effect with decreasing NRM and could be a favorable CBT conditioning regimen for patients with AML in CR.

Myoepithelial carcinoma of major salivary glands: Analysis of population-based clinicopathologic and prognostic features

BackgroundThis study aimed to investigate the effect of demographic characteristics and disease stage on the survival outcomes of patients with myoepithelial carcinoma (MECA) of the salivary glands, and to assess the role of radiotherapy in these patients. MethodsThe Epidemiology, Surveillance and End Results database was queried from 2000 to 2018 to identify patients with MECA. Data pertaining to the tumor stage, size, histological grade, and demographic characteristics were analyzed. The relationship between clinicopathological features and overall survival (OS) was assessed using statistical analyses. ResultsIn total, 290 patients (137 men and 153 women) were identified. The parotid gland was the most common tumor location (76.6% patients). Approximately half of the patients had locally advanced tumors, and 14.5 and 6.6% had lymph node and distant organ involvement, respectively. The median OS was 142 months, while the survival rates at 120 months and 180 months were 53% and 39%, respectively. In the cohort, 160 patients (55.2%) underwent surgery alone, while 130 patients (44.8%) underwent surgery combined with radiotherapy. Multivariate Cox analysis revealed that histopathological grade, stage, T3 stage (hazard ratio [HR]: 2.47, P = 0.039), T4 stage (HR: 3.33, P = 0.011), N2 stage (HR: 6.59, P = 0.002), and M1 stage (HR: 2.72, 95%confidence interval [CI]: 1.03–7.19; P = 0.044) were associated with poor prognosis. Radiotherapy (HR: 0.58, P = 0.042) was a favorable factor for OS, and it reduced the mortality risk by 42%. ConclusionsHistological grade, stage, and radiotherapy are independent risk factors for OS. The decision to administer chemotherapy for MECA should be made with caution. Adjuvant radiotherapy is recommended in high-risk patients.

Optimal management of lenvatinib therapy for patients with unresectable hepatocellular carcinoma by balancing the therapeutic effect with the relative dose intensity.

We aimed to assess the optimal management of first or later-line lenvatinib therapy (LEN) for patients with unresectable hepatocellular carcinoma (uHCC), by clarifying the difference of degree between relative dose intensity (RDI) to achieve objective response (OR) and disease control (DC) by aiming at stable disease (SD), taking dose modifications into consideration. One hundred uHCC patients who received LEN in first- or later-line settings, between April 2018 and December 2020 in our hospital were analyzed retrospectively. The factors associated with overall survival (OS), time to progression (TTP), OR and DC were assessed. The optimal cut-off values of RDI 4weeks after initiation of LEN (RDI during cycle 1) and total RDI (RDI during all cycles) to predict achievement of OR and DC by aiming at SD were determined by receiver operator curve analysis. Achievement of OR and SD were favorable factors for OS (HR, 0.080 and 0.20) and TTP (HR, 0.052 and 0.073), with progressive disease defined as the reference. RDI ≥ 0.8 during cycle 1 and RDI ≥ 0.4 during cycle 1 contributed to achievement of OR (odds ratio, 3.28) and DC (odds ratio, 4.85), respectively. Experience of dose interruption was associated with a favorable TTP (HR, 0.58). The therapeutic line of LEN did not contribute to OS, TTP or best response. To achieve OR and SD for a favorable outcome of first- or later-line LEN, high and moderate early-phase RDI are required, respectively. The degree of RDI during LEN and tolerance need compatible by dose modifications.

Thrombomodulin expression impacts the recurrence and long-term survival in pancreatic cancer.

BackgroundPancreatic cancer is one of the most aggressive digestive cancers. The tumor expression of thrombomodulin (TM) is correlated with favorable prognosis in several types of cancer. However, this correlation has not been confirmed in hepato‐pancreato‐biliary cancer. The aim of this study was to evaluate the prognostic value of TM expression in resected pancreatic ductal adenocarcinoma.MethodsThe data of patients who underwent pancreatic resection for pancreatic invasive ductal adenocarcinoma were obtained from a prospectively maintained database. A total of 131 patients were included. Paraffin sections of tumor tissues were stained immunohistochemically using TM antibody. The patients were divided into two groups: the TM‐positive or TM‐negative group.ResultsThe specimens were TM‐positive in 72 cases. TM expression was a significant factor of favorable prognosis in univariate analysis for disease‐free (DFS) and overall survival (OS). The median OS in the TM‐positive patients was 32.9 mo, which was better than the 20.0 mo in TM‐negative patients (P =.006). TM positivity retained its significance on multivariate analysis for DFS (hazard ratio [HR] 0.651, 95% confidence interval [CI] 0.433–0.979, P =.039) and OS (HR 0.569, 95% CI 0.376–0.862, P =.008).ConclusionsThe tumor expression of TM is a favorable factor for OS in resected pancreatic invasive ductal adenocarcinoma.

Efficacy of nivolumab versus molecular-targeted therapy as second-line therapy for metastatic renal cell carcinoma: Real-world data from two Japanese institutions.

To compare the efficacy of nivolumab with that of molecular-targeted therapy as a second-line therapy for metastatic renal cell carcinoma using real-world data. We retrospectively evaluated patients who received nivolumab or molecular-targeted therapy after the failure of first-line molecular-targeted therapy between January 2008 and December 2019 at two Japanese institutions. Progression-free survival and overall survival after the initiation of second-line therapy were calculated using the Kaplan-Meier method and compared using the log-rank test. Objective response rate was assessed based on the Response Evaluation Criteria in Solid Tumors version 1.1. Among 159 patients, 43 (27%) and 116 (73%) patients received nivolumab and molecular-targeted therapy as second-line therapy, respectively. During follow up (median 11.1months), 129 (81%) and 98 (62%) patients had disease progression and died, respectively. Progression-free survival was comparable between the two treatments (median 5.06 vs 5.95months, P=0.881), whereas overall survival was significantly longer with nivolumab than with molecular-targeted therapy (not reached vs 13.0months, P=0.0008). Multivariate analysis further showed that nivolumab therapy was an independent favorable factor for overall survival (hazard ratio 0.33, P=0.0007). In 151 patients with eligible radiographic data, the objective response rate was significantly higher in nivolumab than in molecular-targeted therapy (n=14/41 [34%] vs n=20/110 [18%], P=0.0485). Real-world data analysis suggests superior efficacy of nivolumab over molecular-targeted therapy as second-line therapy for metastatic renal cell carcinoma.

Allogeneic Hematopoietic Stem Cell Transplantation Overcomes the Poor Prognosis in MLL-Rearranged Solid Tumor Therapy Related-Acute Myeloid Leukemia

BACKGROUND: MLL rearrangement is very common in solid tumor therapy-related acute myeloid leukemia (t-AML). This study investigated the prognosis of MLL t-AML. METHODS: Patients with solid tumor t-AML and MLL de novo AML were enrolled in this retrospective study. The patients were divided into 3 groups: non-MLL t-AML(n=41), MLL t-AML(n=18) and MLL de novo AML(n=98). RESULTS: Of the 157 patients enrolled, 150 patients underwent anti-leukemia therapy. The complete remission (CR) rate was 83.3%, 85.5% and 86.2%(P=0.251), respectively, in MLL t-AML, non-MLL t-AML and MLL AML groups. The 3-years overall survival (OS) was 37.5%, 21.5% and 20.4% (P=0.046). The 3-years leukemia-free survival (LFS) was 28.0%, 32.2% and 22.7% (P=0.031), and the incidence of relapse was 30.0%, 50.4% and 53.5% (P=0.382), respectively, in the three groups. Multivariate analysis revealed that MLL t-AML was a risk factor while allo-HSCT a protective factor for relapse, LFS, and OS (P=0.005, P&amp;lt;0.001 and P&amp;lt;0.001) (P&amp;lt;0.001, P&amp;lt;0.001 and P=0.002, respectively). The 3-years OS was 0%, 17.9% and 0%(P=0.038), LFS was 0%, 23.1% and 0%(P=0.017), and relapse was 100%, 53.1% and 74.4% (P=0.001), respectively among three groups in patients undergoing chemotherapy alone, while OS was 64.3%, 52.7% and 40.7% (P=0.713), LFS was 60.0%, 48.8% and 37.0% (P=0.934), and relapse was 25.0%, 47.4% and 47.5% (P=0.872), respectively, among these group in the patients undergoing allo-HSCT. Intriguingly, MLL t-AML was no longer risk factor for relapse and LFS (P=0.882 and P=0.484, respectively), while it became a favorable factor for OS (P=0.011) in the patients undergoing allo-HSCT CONCLUSIONS: MLL t-AML had poor prognosis compared with non-MLL t-AML and MLL de novo AML,, but allo-HSCT might overcome the poor prognosis of MLL t-AML. Disclosures Liu: Nanfang Hospital, Southern Medical University: Research Funding.

Colorectal cancer under 20\xa0years old: a retrospective analysis from three tertiary hospitals

PurposeColorectal cancer (CRC) rarely occurs in children and adolescents. This study aimed to perform a retrospective analysis and disclose more detailed information about CRC in patients under 20 years old.MethodsMedical records of CRCs in patients under 20 years old referred to three tertiary hospitals in China from September 2000 to July 2019 were retrospectively reviewed. Clinicopathological characteristics, treatment processes and laboratory findings were summarized and treatment outcomes and prognostic factors were analyzed.ResultsA total of 33,394 CRC medical records were analyzed, and we identified seventy (0.21%) CRCs in patients under 20. The most common primary tumor location was the left hemicolon (35.7%). The prominent pathological types were mucinous adenocarcinoma (22.9%) and signet ring cell carcinoma (22.9%). Nearly half (47.1%) of the patients presented with distant metastasis at diagnosis. The fractions of patients with deficient mismatch repair (dMMR) protein expression and microsatellite instability-high (MSI-H) were 23.8% (5/21) and 71.4% (5/7), respectively. Forty-four patients underwent radical surgery. Fifty-five patients received chemotherapy and six patients received radiotherapy. One dMMR/MSI-H rectal cancer patient received immunotherapy and achieved a clinically complete response. The median overall survival (OS) time was 80 months. The 3-year and 5-year OS rates were 61.8% and 57.2%, respectively. An absence of distant metastasis was a favorable factor for OS. For stage II/III CRCs, classic adenocarcinoma and radical surgery were favorable factors for OS. For stage IV CRCs, primary location at the colon was a favorable factor for OS.ConclusionChild and adolescent CRC patients are likely to have distant metastasis, undifferentiated, left hemicolon location, and a dMMR/MSI-H phenotype at diagnosis. Additional efforts are needed to improve their survival outcomes.

Adverse Factors of Treatment Response and Overall Survival in Pediatric and Adult Patients with Pineoblastoma.

ObjectiveIntracranial pineoblastomas are rare neoplasms with poor prognosis. The aim of this study was to describe the independent prognostic factors and treatment strategies for overall survival in pediatric and adult patients.MethodsSixty-four patients were surgically treated between January 2012 and December 2018.ResultsThe series included 37 (57.8%) males and 27 (42.2%) females. Gross total resection was achieved in 41 (64.1%) cases, and the 1-, 3-, and 5-year rates of overall survival were 86.3, 52.3, and 36.6%, respectively. In the pediatric group (n=42), 28 patients (66.7%) were male, with the median, and the mean age was 4 and 6.2±4.7 years, respectively. After a median follow-up of 25.0 months, twenty-six patients (61.9%) died, and the 1-, 3-, and 5-year rates of overall survival were 84.9, 46.4, and 26.7%, respectively. Postoperative radiotherapy (p=0.058) and postoperative chemotherapy (p=0.183) had a positive influence on the increased overall survival. Meanwhile, postoperative radiotherapy combined with chemotherapy following surgery had a positive impact on overall survival (p=0.174, Log rank). In the adult group, the mean overall survival was 67.3±9.3 months (range, 0.8–95.3 months), and the 1-, 3-, and 5-year rates of overall survival were 89.5, 64.4, and 64.4%, respectively. In this group, no statistical association was observed between clinical factors and outcomes. However, patients who received postoperative radiotherapy (60.7 vs 57.6 month, mean survival; p=0.510, Log rank) or chemotherapy (63.0 vs 59.9 month, mean survival; p=0.404, Log rank) had better survival rates compared with those who declined.ConclusionIn the pediatric group, surgery with postoperative radiotherapy and chemotherapy was a favorable factor for overall survival. In the adult group, a positive trend in overall survival was found when patients received radiation and/or chemotherapy following surgery.

Identification of biomarkers for personalized peptide vaccination in 2,588 cancer patients.

Peptide-based cancer vaccines have failed to provide sufficient clinical benefits in order to be approved in clinical trials since the 1990s. To understand the mechanisms underlying this failure, the present study investigated biomarkers associated with the lower overall survival (OS) among 2,588 patients receiving personalized peptide vaccination (PPV). Survival data were obtained from a database of 2,588 cancer patients including 399 patients with lung, 354 with prostate and 344 with colon cancer. They entered into phase II clinical trials of PPV in which 2 to 4 of 31 warehouse peptides were selected for vaccination on an individual patient basis based on human leukocyte antigen (HLA) class IA-types and pre-existing peptide-specific IgG levels. Higher pre-vaccination neutrophil, monocyte and platelet counts, and lower pre-vaccination lymphocyte and red blood cell counts were inversely associated with OS, with higher sensitivities in the proportions of neutrophils and lymphocytes, respectively. The most potent unfavorable and favorable factors for OS were the median percentage of neutrophils (>64.8%) or percentage of lymphocytes (>25.1%) with correlation coefficients (R2) of 0.98 and 0.92, respectively. Higher pre-vaccination levels of c-reactive protein and other inflammatory soluble factors were inversely associated with OS. Pre-vaccination peptide-specific immunity levels had no effect on OS, although lower immune boosting levels were inversely associated with OS. None of the 31 peptides was inversely associated with OS, although a few peptides were positively associated with it. On the whole, the findings of the present study suggested that pre-vaccination inflammatory signatures, but not those of post-vaccination immune induction, were associated with lower clinical benefits of PPV.