Disease-free Survival Rates Of Patients Research Articles

Clear surgical margins as a prognostic indicator for disease recurrence, with no impact on survival rates in patients with myxofibrosarcoma

Myxofibrosarcoma presents an infiltrating growth pattern that results in a high tendency for local recurrence. Clear margin resection is challenging because of microscopic infiltration. The purpose of the present study was to analyze the overall and disease-free survival rates of patients with myxofibrosarcoma and the prognostic factors that determine both survival and disease recurrence. Among the 111 patients included in our study, the 5-year overall survival rate was 65.5%. An age of more than 65 years (hazard ratio [HR] 1.9 [95% confidence interval (CI) 1.4–5.6]; p < 0.001), a tumor size of more than 5 cm (HR 2.8 [95% CI 0.9–8.1]; p = 0.049) and the G3 tumor grade (HR 14.1 [95% CI 2.1–105.0]; p < 0.001) negatively affected overall survival. The 5-year recurrence-free survival rate was 49.4%. R1/R2-type resection (HR 2.4 [95% CI 1.0–5.6]; p = 0.048) had a detrimental effect on tumor recurrence. Clear margins had a positive impact on recurrence-free survival, but did not significantly affect overall patient survival, suggesting that other factors may play a more significant role in determining patient outcomes. A surgical margin of 2 mm was not sufficient to significantly influence the incidence of recurrence. Consequently, a wider surgical margin may be necessary to reduce the risk of myxofibrosarcoma recurrence.

Sublobectomy and lymph node sampling are adequate for patients with invasive lung adenocarcinoma presenting as pure ground glass nodules.

In this study, we aimed to investigate the prognosis of invasive lung adenocarcinoma that manifests as pure ground glass nodules (pGGNs) and confirm the effectiveness of sublobectomy and lymph node sampling in patients with pGGN-featured invasive adenocarcinoma (IAC). We retrospectively enrolled 139 patients with pGGN-featured IAC, who underwent complete resection in two medical institutions between January 2011 and May 2022. Stratification analysis was conducted to ensure balanced baseline characteristics among the patients. The 5-year overall survival (OS) and disease-free survival (DFS) rates were compared between the groups using Kaplan-Meier survival curves and log-rank test. The 5-year OS and DFS rates for patients with IAC presenting as pGGNs after surgery were 96.5% and 100%, respectively. No lymph node metastasis or recurrence was observed in any of the enrolled patients. There was no statistically significant difference in the 5-year OS between patients who underwent lobectomy or sublobectomy, along with lymph node resection or sampling. IAC presented as pGGNs exhibited low-grade malignancy and had a relatively good prognosis. Therefore, these patients may be treated with sublobectomy and lymph node sampling.

Site-Specific Differences of Eligibility for Adjuvant Immunotherapy Among Urothelial Carcinoma Patients Treated With Radical Surgery: Results From a Multicenter Cohort Study

BackgroundThe CheckMate274 trial has reported enhanced disease-free survival rates in patients with stage pT3–4/ypT2–4 or pN+ urothelial carcinoma (UC) undergoing adjuvant nivolumab therapy. This study compares prognostic differences between urothelial carcinoma of the bladder (UCB) and upper tract urothelial carcinoma (UTUC). MethodsWe retrospectively analyzed data from 719 patients with UC who underwent radical surgery, stratifying to patients at stage pT3–4 and/or pN+ without neoadjuvant chemotherapy (NAC) or at ypT2–4 and/or ypN+ with NAC (potential candidates for adjuvant immunotherapy), and to those who were not candidates for adjuvant immunotherapy. We used Kaplan–Meier curves to assess oncological outcomes, particularly nonurothelial tract recurrence-free survival (NUTRFS), cancer-specific survival (CSS), and overall survival (OS). Risk factors were identified by Cox regression analysis. ResultsKaplan–Meier curves showed significantly lower NUTRFS, CSS, and OS for potential adjuvant immunotherapy candidates than for noncandidates in each UCB and UTUC group. NUTRFS, CSS, and OS did not differ significantly between adjuvant immunotherapy candidates with UBC or UTUC. Trends were similar among patients ineligible for adjuvant immunotherapy. Pathological T stage (pT3–4 or ypT2–4), pathological N stage, and lymphovascular invasion (LVI) were independent predictors of oncological outcomes on multivariate analysis. ConclusionThe criteria for adjuvant immunotherapy candidates from the CheckMate 274 trial can also effectively stratify UC patients after radical surgery. Substantial clinical significance is attached to LVI status as well as to pathological T and N status, suggesting that LVI status should be considered when selecting suitable candidates for adjuvant immunotherapy.

The Value of Anterolateral Thigh Free Flap for the Reconstruction of Malignant Melanoma of the Sole of the Foot.

Wide excision of malignant melanoma on the foot usually results in an extensive function-destroying defect, and the reconstruction of foot defects remains challenging for reconstructive surgeons. We propose using anterolateral thigh perforator (ALT) free flaps for the reconstruction of widespread defects caused by malignant melanoma in the sole. This retrospective study included 34 patients who underwent reconstruction of sole defects caused by malignant melanoma resection with 35 ALT perforator free flaps between August 2005 and July 2021. In total, 18 male patients and 16 female patients were included (mean age at surgery, 65.4 years). The mean size of the flaps was 100.4 cm 2 . Thirty-three of the 35 flaps survived. Hematoma, seroma, and chronic ulceration were not identified in any cases. All patients achieved independent ambulation within the follow-up period, except 1 patient with gait discomfort. The 5-year overall and disease-free survival rates of patients were 64.4% and 56.6%, respectively. The ALT flap is a versatile surgical option that should be considered for reconstruction of the sole after malignant melanoma resection, considering its various surgical advantages and the functional aspects of independent ambulation, the aesthetic aspects of wearing conventional footwear, and the anatomical aspects of the sole.

Combined inflammatory parameters and tertiary lymphoid structure predict prognosis in patients with resectable non-small cell lung cancer treated with neoadjuvant chemoimmunotherapy.

Neoadjuvant chemoimmunotherapy shows great potential for patients with non-small cell lung cancer (NSCLC), but no clear prognostic markers have been identified. This study investigates the correlation between inflammatory parameters and the expression of tertiary lymphoid structures (TLS) and the predictive ability of inflammatory parameters combined with TLS for disease-free survival (DFS) in patients with resectable NSCLC receiving neoadjuvant chemotherapy. We retrospectively analyzed the clinical data and hematological parameters of 117 patients with NSCLC who underwent neoadjuvant chemoimmunotherapy and radical surgery. TLS were evaluated by observing H&E stained and immunohistochemically stained tissue sections. Univariate chi-square and multifactor logistic analyses were used to determine the correlation between hematological parameters and TLS. The Kaplan-Meier method, univariate and multivariate Cox regression analysis and constructed nomogram models were used to assess the prognostic value of the investigated parameters on DFS. Receiver operating characteristic (ROC) curves analyses were used to compare the performances of the three models. After logistic analysis, it was found that platelet-to-lymphocyte ratio (PLR) ≤288.78 (odds ratio OR=0.122, P=0.009) was an independent predictor of high TLS expression. The Cox regression analyses showed that Histology (HR=0.205, P=0.002), systemic immune inflammation index (SII) (HR=2.758, P=0.042) and TLS (HR=0.057, P<0.05) were independent prognostic factors in patients with NSCLC. The combined SII-TLS model was better than the single-indicator model in assessing the 1-year and 18-months DFS rates in patients with NSCLC. Our study showed that PLR was an independent predictor of TLS and that both TLS and SII predicted prognosis in patients with neoadjuvant chemoimmunotherapy-resectable NSCLC; however, combining SII and TLS to assess DFS was more accurate than using either parameter alone.

Efficacy analysis of surgical combined with postoperative adjuvant therapy for T3 gallbladder carcinoma: a multicenter retrospective study

Objective: To explore the clinical value of adjuvant therapy in patients with T3 gallbladder cancer (GBC) who have undergone R0 resection. Methods: Clinical and pathological data from 415 patients with T3 GBC who underwent surgical treatment in 7 tertiary centers in China from January 2013 to December 2018 were collected,including 251 males and 164 females,aged (61±11)years (range: 26 to 88 years). Depending on whether to receive adjuvant therapy after radical resection,the patients were divided into the radical resection group alone (group A,n=358) and the radical resection combined with the postoperative adjuvant therapy group (group B,n=57). The general data of the two groups were matched 1∶1 by propensity score matching method,and the caliper value was 0.02.Clinicopathological characteristics,overall survival and disease-free survival of the two groups were compared.The Cox regression model was used for multivariate analysis,and patients with at least one or more independent risk factors were classified as high-risk clinicopathological subtypes. Subgroup analysis was performed to assess the clinical value of adjuvant therapy after radical resection in patients with high-risk clinicopathological subtypes. Results: After the matching,there were 42 patients in each of the two groups. The incidence of gallbladder cancer and the number of dissected lymph nodes in group B after cholecystectomy were higher than those in group A (χ2=9.224,2.570,both P<0.05). There were no significant differences in overall survival rate and disease-free survival rate between the two groups before and after matching (all P>0.05). The results of the univariate and multivariate analysis showed that CA19-9>39 U/ml,nerve invasion,tumor location (liver side or bilateral),TNM stage ⅢB to ⅣB ,poorly differentiated tumor were independent prognostic factors of overall survival and disease-free survival of patients with T3 stage gallbladder cancer (all P<0.05).Three hundred and twenty-nine patients(79.3%) had high-risk clinicopathological subtypes,and the median survival time after curative resection with and without adjuvant therapy was 17 months and 34 months respectively,and the 3-year and 5-year overall survival rates were respectively 40.0%,21.3% and 46.0%,46.0% (χ2=4.042,P=0.044);the median disease-free survival time was 9 months and 13 months,and the 3-year and 5-year disease-free survival rates were 23.4%,13.6% and 30.2%,18.2% (χ2=0.992,P=0.319). Conclusions: Postoperative adjuvant therapy following radical surgery did not yield significant improvements in the overall survival and disease-free survival rates of patients diagnosed with T3 gallbladder cancer. However, it demonstrated a significant extension in the overall survival rate for patients presenting high-risk clinicopathological subtypes.

Contralateral Low-to-Intermediate Suspicion Nodule Is Not a Contraindication for Lobectomy in Patients with Papillary Thyroid Carcinoma.

Background: The optimal extent of surgery for unilateral papillary thyroid carcinoma (PTC) with contralateral nodules remains unclear. This study evaluated the long-term outcomes in a large cohort of patients with unilateral PTC and contralateral low-to-intermediate suspicious nodules who underwent lobectomy. Methods: This retrospective cohort study included patients with unilateral PTC who underwent lobectomy between January 2016 and December 2017 at Asan Medical Center in Korea. Patients were divided into two groups, those with and without contralateral nodules at the time of lobectomy: the Present group and the Absent group. All contralateral nodules observed at the time of surgery and during follow-up were evaluated. Results: The study cohort consisted of 1761 patients (1879 nodules), including 700 (39.8%) with and 1061 (60.2%) without contralateral nodules. The median size of the contralateral nodules was 0.5 cm. After a median follow-up of 59 months, the median growth of the contralateral nodules in the Present group was 0.1 cm (range, -3.4 to 4.7 cm). Of the contralateral nodules present at the time of lobectomy, 54.7% remained unchanged, decreased in size, or disappeared; whereas 14.8% increased ≥0.3 cm. Of the 700 patients with contralateral nodules, 20 (2.9%) were diagnosed with contralateral PTC. The 5-year contralateral PTC disease-free survival rates in patients with and without contralateral nodules were 98.2% and 99.3% (p = 0.003), respectively, whereas the 5-year recurrence-free survival rates did not differ significantly in these two groups. Of the 39 patients who underwent completion thyroidectomy, 2 (5.1%) experienced permanent hypocalcemia. Conclusions: Lobectomy may be a safe and feasible initial treatment option for patients with unilateral low-risk PTC and contralateral low-to-intermediate suspicious nodules.

The mechanism of LSM2 in the progression of live hepatocellular carcinoma was analyzed based on bioinformatics.

Comprehensive analysis of the expression and probable function of LSM2 in Live hepatocellular carcinoma (LIHC), and validation via in vitro experiments. Integrated use of database resources to examine the differential expression, survival prognosis, clinicopathological characteristics, and functional enrichment of LSM2 in LIHC. The expression level of LSM2 in LIHC tissues and adjacent tissues was proven via immunohistochemical staining. The biological function of LSM2 in LIHC was detected by cell proliferation, cell cloning, cell scratch, cell migration, and invasion experiments in vitro. TIMER 2.0 and GEPIA indicated that LSM2 was highly expressed in cancers and was strongly associated with survival rates in LIHC, cholangiocarcinoma, breast cancer, and renal clear cell carcinoma. LSM2 was highly expressed in LIHC, which was closely associated to the clinicopathological characteristics of patients, and the overall survival rate and disease-free survival rate of patients with high expression of LSM2 were lower than those with low expression of LSM2. Functional enrichment results revealed that LSM2 was involved to ribosome formation, DNA replication, cell cycle, metabolic processes, JAK-STAT signaling pathways, and FoxO signaling pathways. Knockdown of LSM2 inhibited the proliferation, migration, and invasion of LIHC cells in vitro experiments. LSM2 was highly expressed in LIHC and was related to a poor prognosis. Knockdown of LSM2 could inhibit the proliferation, migration, and invasion of LIHC cells.

Prognostic stratification of endometrial cancers with high microsatellite instability or no specific molecular profile.

To identify high-risk disease in clinicopathologic low-risk endometrial cancer (EC) with high microsatellite instability (MSI-H) or no specific molecular profile (NSMP) and therapeutic insensitivity in clinicopathologic high-risk MSI-H/NSMP EC. We searched The Cancer Genome Atlas for DNA sequencing, RNA expression, and surveillance data regarding MSI-H/NSMP EC. We used a molecular classification system of E2F1 and CCNA2 expression and sequence variations in POLE, PPP2R1A, or FBXW7 (ECPPF) to prognostically stratify MSI-H/NSMP ECs. Clinical outcomes were annotated after integrating ECPPF and sequence variations in homologous recombination (HR) genes. Data were available for 239 patients with EC, which included 58 MSI-H and 89 NSMP cases. ECPPF effectively stratified MSI-H/NSMP EC into distinct molecular groups with prognostic implications: molecular low risk (MLR), with low CCNA2 and E2F1 expression, and molecular high risk (MHR), with high CCNA2 and E2F1 expression and/or PPP2R1A and/or FBXW7 variants. The 3-year disease-free survival (DFS) rate was 43.8% in the MHR group with clinicopathologic low-risk indicators and 93.9% in the MLR group (P<.001). In the MHR group, wild-type HR genes were present in 28% of cases but in 81% of documented recurrences. The 3-year DFS rate in patients with MSI-H/NSMP EC with clinicopathologic high-risk indicators was significantly higher in the MLR (94.1%) and MHR/HR variant gene (88.9%) groups than in the MHR/HR wild-type gene group (50.3%, P<.001). ECPPF may resolve prognostic challenges for MSI-H/NSMP EC by identifying occult high-risk disease in EC with clinicopathologic low-risk indicators and therapeutic insensitivity in EC with clinicopathologic high-risk indicators.

Validation of a Disease-Free Survival Prediction Model Using UBE2C and Clinical Indicators in Breast Cancer Patients.

To explore the validation of a disease-free survival (DFS) model for predicting disease progression based on the combination of ubiquitin-conjugating enzyme E2 C (UBE2C) levels and clinical indicators in breast cancer patients. We enrolled 121 patients with breast cancer, collected their baseline characteristics and follow-up data, and analyzed the UBE2C levels in tumor tissues. We studied the relationship between UBE2C expression in tumor tissues and disease progression events of patients. We used the Kaplan-Meier method for identifying the disease-free survival rate of patients, and the multivariate Cox regression analysis to study the risk factors affecting the prognosis of patients. We sought to develop and validate a model for predicting disease progression. We found that the level of expression of UBE2C could effectively distinguish the prognosis of patients. In the Receiver Operating Characteristic (ROC) curve analysis, the Area under the ROC Curve (AUC) = 0.826 (0.714-0.938) indicating that high levels of UBE2C was a high-risk factor for poor prognosis. After evaluating different models using the ROC curve, Concordance index (C-index), calibration curve, Net Reclassification Index (NRI), Integrated Discrimination Improvement Index (IDI), and other methods, we finally developed a model for the expression of Tumor-Node (TN) staging using Ki-67 and UBE2C, which had an AUC=0.870, 95% CI of 0.786-0.953. The traditional TN model had an AUC=0.717, and 95% CI of 0.581-0.853. Decision Curve Analysis (DCA) and Clinical Impact Curve (CIC) analysis indicated that the model had good clinical benefits and it was relatively simple to use. We found that high levels of UBE2C was a high-risk factor for poor prognosis. The use of UBE2C in addition to other breast cancer-related indicators effectively predicted the possible disease progression, thus providing a reliable basis for clinical decision-making.

The role of neoadjuvant polychemotherapy in the treatment of patients with stage IIB cervical cancer

Introduction and Aim: More than 85% of cervical cancer (CC) cases are reported in developing countries where access to screening is limited. With localized forms of CC, it is possible to achieve good treatment results using radical procedures compared to locally widespread processes. Methods: This is a retrospective study of 68 patients with stage IIB CC hospitalized from 2013–2022. During the initial treatment and after a full clinical examination, all patients were diagnosed with stage IIB CC, a parametrial and vaginal involvement. Results: Forty-six patients (74%) received two courses of chemotherapy, 14 patients (23%) received three courses, and 2 patients (3%) received four courses. The tumor became resectable after two courses in 46 patients, after 3–4 courses all patients moved on to the next surgical stage. Of the early postoperative complications, 9 patients (14.5%) had bladder atony, which was resolved by the conservative method. Conclusion: Thus, there is a certain category of patients with CC, where it is possible to make the tumor into a resectable form, and this will increase the percentage of the surgical component of treatment, which in turn could increase the 5-year disease-free survival rates of patients with stage IIB CC.

Multiplication of tumor maximum diameter and number as a new surgical indicator for Barcelona Clinic Liver Cancer intermediate-stage hepatocellular carcinoma.

Recent advances in treatment modalities have been made, limiting the indication of hepatic resection in the treatment strategy for hepatocellular carcinoma (HCC) patients. This retrospective study investigated the significance of multiplication of tumor maximum diameter and number (MDN) as a surgical indicator for Barcelona Clinic Liver Cancer intermediate-stage HCC. A total of 49 patients with Barcelona Clinic Liver Cancer intermediate-stage HCC who underwent curative hepatic resection between 2000 and 2020 were enrolled in this study. Prognostic factors of overall survival and disease-free survival, including the product of MDN, were analyzed. Patients with MDN >12 experienced significantly worse prognosis compared with those with MDN ≤12 (p=0.0395), and 5-year overall survival rates after hepatic resection were 60.0% and 23.4%, respectively. Furthermore, the disease-free survival rate of patients with MDN >12 was significantly worse compared with those with MDN ≤12 (p=0.0049), and all patients with MDN >12 experienced recurrence within 3years after hepatic resection. In the multivariate analysis, MDN >12 was identified as the only independent prognostic factor of both overall survival and disease-free survival. In addition, patients with MDN >12 suffered from uncontrollable recurrence by locoregional treatment, such as more than four intrahepatic and extrahepatic recurrences, after hepatic resection. MDN index might be a new surgical indicator for Barcelona Clinic Liver Cancer intermediate-stage HCC, and influence clinical decision-making for individual treatment strategies.

Assessment of the effectiveness of surgical resections following tyrosine kinase inhibitor therapy in patients with EGFR-mutated stage III–IV lung adenocarcinoma

Objective. To assess the overall and disease-free survival rates in patients with EGFR-mutated lung adenocarcinoma, who underwent surgery after achieving the objective response to tyrosine kinase inhibitor (TKI) therapy.Material and Methods. The overall and disease-free survival rates were analyzed in 18 patients with EGFR-positive lung adenocarcinoma, which was inoperable at presentation due to locally advanced disease or the evidence of distant metastasis. In accordance with the clinical standards, patients were recommended for TKI therapy. Surgical resection was performed after achieving the objective tumor response to TKI therapy. The control group included 23 patients with EGFR mutation-positive lung adenocarcinoma, who did not undergo surgery after receiving TKI therapy.Results. The study revealed a statistically significant effect of surgical resection on the overall survival (OS) in patients with EGFR mutation-positive stage III–IV lung adenocarcinoma after response to TKI therapy (p=0.004). However, there was no statistically significant effect on the disease-free survival (DFS) (p=0.40). There was a tendency to increase in the median OS in patients of the study group (46 months) compared to that in patients of the control group (26 months). Surgery in the study group was characterized with some technical difficulties associated with severe fibrosis. However, this did not affect the duration of surgery and the volume of blood loss.Conclusion. Tumor resection in patients with EGFR mutation-positive stage III–IV lung adenocarcinoma is feasible and safe, but requires highly qualified team surgeons in well-equipped medical centers. Our study revealed that the combination of EGFR-TKI and tumor resection provided better PFS and OS than EGFR-TKI alone. However, further studies are required.

Prognostic factors in resected pulmonary carcinoid tumors: A retrospective study with 10 years of follow‑up.

The objective of the present study was to characterize the difference in 10-year carcinoid-specific survival (CSS) and disease-free survival (DFS) among patients with resected pulmonary typical carcinoid (TC) and atypical carcinoid (AC). Patients diagnosed with pulmonary carcinoid tumors (PCT) between January 1, 1997, and December 31, 2016, were identified. All patients underwent video-assisted thoracoscopic surgery or thoracotomy with thoracic lymphadenectomy. Cumulative CSS was estimated using the Kaplan-Meier model. The analysis of hazard ratios (HRs) and 95% confidence intervals (CIs) was performed using univariate and multivariate Cox proportional hazards models. A total of 404 patients with PCT were included in the present study. The 10-year CSS and DFS rates of patients with AC were significantly worse than those of patients with TC (49.1 vs. 86.8% and 52.2 vs. 92.6%, respectively; P<0.001). In the CSS multivariate analysis, older age and lymph node involvement (HR, 2.45; P=0.022) were associated with worse survival in AC, while age, male sex, M1 stage, cigarette smoking and inadequate N2 lymphadenectomy were associate with worse survival in TC. In the recurrence multivariate analysis, N1-3 stage (HR, 2.62; 95% CI, 1.16-5.95; P=0.018) and inadequate N2 lymphadenectomy (HR, 2.13; 95% CI, 1.04-4.39; P=0.041) were associated with an increase in recurrence in AC, while male sex (HR, 3.72; 95% CI, 1.33-10.42; P=0.010) and M1 stage (HR, 14.93; 95% CI, 4.77-46.77; P<0.001) were associated with an increase in recurrence in TC. In conclusion, patients with AC tumors had significantly worse CSS and DFS rates compared with patients with TC. The degree of nodal involvement in AC was a prognostic marker, in contrast to that in TC. Inadequate lymphadenectomy increased the risk of recurrence in AC and mortality in TC, although surgical approaches did not have a significant impact. The present study therefore emphasizes the importance of mediastinal nodal dissection in patients with PCTs.

Expression of Programmed Death-1 Ligand in Renal Cell Carcinoma and Its Relationship with Pathologic Findings and Disease-Free Survival

Background: Renal cell carcinoma (RCC) is an invasive malignancy of kidney origin. The programmed death-1 ligand (PD-L1) with its receptor (PD-1) on T-cells can inactivate antitumor response and possibly lead to poor outcomes in patients with RCC. Methods: Our study assessed the expression of PD-L1 by immunohistochemical staining on 86 radical or partial nephrectomy samples with RCC diagnoses with diverse types, tumor grades, and stages. Tumor specimens were collected from the pathology archive of 2014 - 2017 in Sina Hospital, Tehran, Iran. Results: Out of 86 studied RCC samples, 68 cases (79.1%) were clear cell types. PD-L1 expression was observed more in non-clear cell carcinoma samples than in clear cell carcinoma (P = 0.008). PD-L1 expression had significant relationships with nuclear grade and tumor necrosis (P = 0.025 and 0.010, respectively). However, PD-L1 expression was not correlated with tumor size, lymphovascular invasion, and sarcomatoid differentiation. The disease-free survival rate in patients with PD-L1 expression was significantly less than in patients with PD-L1 negative staining (P = 0.032). Conclusions: According to our findings, PD-L1 could be regarded as an important biomarker with worse prognosis and aggressive clinicopathologic findings in patients with RCC.

PARPi treatment enhances radiotherapy-induced ferroptosis and antitumor immune responses via the cGAS signaling pathway in colorectal cancer

In cancer cells, poly (ADP-ribose) polymerase (PARP)-1 and PARP2 initiate and regulate DNA repair pathways to protect against DNA damage and cell death caused by radiotherapy or chemotherapy. Radiotherapy and PARP inhibitors (PARPis) have been combined in clinical trials, but their action mechanisms remain unclear. Here, we show that activated by ionizing radiation (IR) generated dsDNA, cyclic GMP-AMP synthase (cGAS) signaling promoted regulated cell death, specifically ferroptosis, via the activating transcription factor 3 (ATF3)–solute carrier family 7 member 11 axis and the antitumor immune response via the interferon-β-CD8+ T cell pathway. Niraparib, a widely used PARPi, augmented cGAS-mediated ferroptosis and immune activation. In colorectal cancer models, cGAS knockdown (KD) compromised IR-induced ferroptosis via downregulation of ATF3 (key ferroptosis regulator) expression. cGAS depletion reversed IR-induced infiltration of CD8+ T or CD8+GZMB+ T cells in the cGAS KD group. Survival analysis of paired tumor samples before and after standard radiotherapy revealed that high expression levels of cGAS, ATF3, and PTGS2 and high density of CD8+ T cells resulted in a significantly high disease-free survival rate in patients with rectal cancer. Therefore, PARPi treatment increases the cytoplasmic accumulation of dsDNA caused by IR, triggering the cGAS signaling-mediated tumor control in cancer cell lines and mouse xenograft models.

Effect of ruxolitinib combined with glucocorticoid on cytomegalovirus activation in acute graft-versus-host disease

Objective: To observe the effect of ruxolitinib combined with glucocorticoid on cytomegalovirus (CMV) activation in patients with acute graft-versus-host disease (aGVHD) . Methods: The clinical data of 195 patients who underwent allogeneic hematopoietic stem cell transplantation in the Department of Hematology of the First Medical Center of the People's Liberation Army General Hospital from August 2018 to September 2020 were retrospectively analyzed. According to the severity of aGVHD, the patients were divided into the non-GVHD group, aGVHD grade Ⅰ group, aGVHD grade Ⅱ-Ⅳ group, and aGVHD grade Ⅲ/Ⅳ group. In addition, they were classified into two subgroups according to the first-line treatment regimen for aGVHD: combined regimen group (ruxolitinib combined with glucocorticoid) and classical regimen group (glucocorticoid alone) . The cumulative incidence of CMV activation, the duration of CMV activation, and the duration of CMV negativity in each subgroup at 90 and 180 days after transplantation were analyzed. The overall survival and disease-free survival rates of patients in both regimens were compared. Results: Sixty-four (32.8%) patients in the group did not develop aGVHD. The numbers of patients with grade Ⅰ, Ⅱ-Ⅳ, and Ⅲ/Ⅳ aGVHD were 30 (15.4%) , 101 (51.8%) , and 14 (7.2%) , respectively. Compared with patients in the classical regimen, no significant difference was observed in the cumulative incidence of CMV activation, duration of CMV activation, and duration of CMV negativity in patients with grade Ⅰ-Ⅳ aGVHD in the combined regimen at 90 and 180 days after transplantation (P>0.05) . Further analysis of patients with grade Ⅱ-Ⅳ and Ⅲ/Ⅳ aGVHD showed that the cumulative incidence of CMV activation, duration of CMV activation, and duration of CMV negativity did not show significant difference between the two treatment regimens (P>0.05) . In addition, there was no significant difference in the overall survival and disease-free survival rates of patients in both regimens (P>0.05) . Conclusion: Ruxolitinib combined with glucocorticoid as the first-line therapy for aGVHD did not increase the risk of CMV activation.

Efficacy of the No. 10 lymphadenectomy with spleen preservation on patients with gastric cancer and/or esophagogastric junction adenocarcinoma who underwent total gastrectomy: a systematic review and meta-analysis.

BackgroundSurgery with total gastrectomy and D2 lymph node dissection (LND) has been recommended as the standard treatment for patients with advanced upper and middle gastric carcinoma and/or Siewert type II/III adenocarcinoma of the esophagogastric junction (AEG). However, whether the No. 10 lymph node (No. 10 LN, also known as splenic hilar LN) should be dissected in total gastrectomy remains controversial. We aimed to evaluate whether the No. 10 LND with spleen preservation has survival benefit for patients with gastric cancer and/or AEG who underwent the total gastrectomy.MethodsThe PubMed, Embase, the Cochrane Library, ClinicalTrials.gov and American Society of Clinical Oncology.org (ASCO.org) were electronically searched to identify eligible studies. The primary outcome was the survival rate, and secondary outcomes included the disease-free survival (DFS) rate and side effects. The Review Manager 5.3.5 software was used for the meta-analysis. The odds ratio (OR) and mean difference with 95% confidence interval (CI) were calculated. The statistical heterogeneity was assessed using chi-square (χ2) and I2 tests.ResultsEight studies enrolling a total of 4,131 patients were eligible for our review. The meta-analysis results demonstrated that the No. 10 LND group was significantly better than the non-No. 10 LND group in terms of the 3- (OR =0.71, 95% CI: 0.62–0.81, P<0.00001) and the 5-year (OR =0.66, 95% CI: 0.58–0.75, P<0.00001) survival rates but not in the 1-year survival rate (OR =0.91, 95% CI: 0.75–1.11, P=0.36). The DFS rates in the No. 10 LND group were significantly increased after 1 (OR =0.76, 95% CI: 0.61–0.93, P=0.008), 3 (OR =0.69, 95% CI: 0.60–0.81, P<0.00001), and 5 (OR =0.66, 95% CI: 0.56–0.76, P<0.00001) years compared with those in the non-No. 10 LND group.DiscussionEvidence shows that the No. 10 LND with spleen preservation can improve the survival and the DFS rates for patients with gastric cancer and/or Siewert type II/III AEG who underwent the total gastrectomy. High-quality prospective trials are expected.

Clinical Safety and Effectiveness of Robotic-Assisted Surgery in Patients with Rectal Cancer: Real-World Experience over 8 Years of Multiple Institutions with High-Volume Robotic-Assisted Surgery.

Simple SummaryThe aim of this retrospective observational study was to evaluate perioperative and short-term oncological outcomes of robotic-assisted rectal surgery (RRS) in hospitals with a high-volume of robotic-assisted surgeries. This study enrolled patients with rectal adenocarcinoma undergoing RRS from three high-volume institutions from December 2011 to June 2020. Compared with other studies, our results revealed the equivalent or superior perioperative and short-term oncological outcomes. Hence, RRS is an effective, safe, and feasible technique for patients with rectal cancers in high-volume hospitals.The perioperative and short-term oncological outcomes of robotic-assisted rectal surgery (RRS) are unclear. This retrospective observational study enrolled patients with rectal adenocarcinoma undergoing RRS from three high-volume institutions in Taiwan. Of the 605 enrolled patients, 301 (49.75%), 176 (29.09%), and 116 (19.17%) had lower, middle, and upper rectal cancers, respectively. Low anterior resection (377, 62.31%) was the most frequent surgical procedure. Intraoperative blood transfusion was performed in 10 patients (2%). The surgery was converted to an open one for one patient (0.2%), and ten (1.7%) patients underwent reoperation. The overall complication rate was 14.5%, including 3% from anastomosis leakage. No deaths occurred during surgery and within 30 days postoperatively. The positive rates of distal resection margin and circumferential resection margin were observed in 21 (3.5%) and 30 (5.0%) patients, respectively. The 5-year overall and disease-free survival rates for patients with stage I–III rectal cancer were 91.1% and 86.3%, respectively. This is the first multi-institutional study in Taiwan with 605 patients from three high-volume hospitals. The overall surgical and oncological outcomes were equivalent or superior to those estimated in other studies. Hence, RRS is an effective and safe technique for rectal resection in high-volume hospitals.

Tumor-infiltrating ICOS+ Effector Regulatory T-Cells in Oral Squamous Cell Carcinoma as a Promising Biomarker for Prognosis and 'Hot' Tumor.

Tumor immunity in the tumor microenvironment is activated in patients with feasible clinical responses to immune checkpoint inhibitors. The immunological profile of tumor-infiltrating lymphocytes (TILs) obtained from patients with oral squamous cell carcinoma (OSCC) was examined in relation to their prognosis. Surface antigens, including immune checkpoint molecules, on TILs from 31 patients with primary OSCC were analyzed by flow cytometry. The activation status of TILs was examined through a heatmap analysis and unsupervised clustering classified patients into groups with activated or inactivated TILs. A supervised machine-learning algorithm for single-cell analyses in relation to prognosis was run using the Cluster Identification, Characterization, and Regression (CITRUS) program. None of surface antigens were related to prognosis. The CITRUS program revealed a relationship between CD45RA-CD4+ CD25high inducible T-cell co-stimulator (ICOS)+ TILs and recurrence, and also identified a similar fraction significantly specific to the group with activated TILs. The disease-free survival rate for patients with ≥95% ICOS+ TILs was significantly lower than that for those with <95% ICOS+ TILs. Furthermore, a review of clinicopathological factors related to prognosis identified the percentage of ICOS+ TILs to be an independent prognostic factor for patients with OSCC. CD25highICOS+ regulatory T-cells in TILs have potential as a biomarker for predicting recurrence after surgical treatment and clinical responses to immune checkpoint inhibitors in patients with OSCC.