Significant Prognostic Factor For Disease-free Survival Research Articles

Clinical characteristics and prognostic factors of male breast cancer in China.

This study aimed to explore the clinical characteristics of male breast cancer (MBC) patients and the factors influencing their prognosis. We conducted a retrospective case series analysis of 117 MBC cases who were treated at Zhejiang Cancer Hospital from 2009 to 2022. Cox proportional hazard model was used to identify prognostic factors of MBC. Nomogram was constructed based on these factors, which was further evaluated by C-index and calibration curves. A total of 115 MBC cases were finally included in our analyses, with median diagnosis age of 59 years. Of these cases, 80.0% were estrogen receptor (ER) positive, 79.2% were progesterone receptor (PR) positive, 48.7% were human epidermal growth factor receptor 2 (HER2) negative, and 42.6% had Ki67 levels higher than 15%. 108 (93.9%) cases underwent radical mastectomy, while only 3 (2.6%) received breast-conserving surgery. The Logrank test suggested that lymphocyte-to-monocyte ratio (LMR) was negatively associated with both overall survival (OS) and disease-free survival (DFS) of MBC, while platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) were only positively associated with OS (all P-values < 0.05). Multivariate regression analysis showed that age (HR 1.08, 95% CI 1.03-1.13) was significant prognostic factors for OS. Meanwhile, age (HR 1.06, 95% CI 1.02-1.10), histological differentiation grade (poorly differentiated/undifferentiated vs. well-differentiated: HR 2.55, 95% CI 1.05-6.17), and TNM stage (IV vs. I: HR 31.59, 95% CI 6.01-165.93) were also significant prognostic factors for DFS. Nomograms were developed for DFS, with C-indexes of 0.782, indicating good predictive performance. Increased age, bigger tumor size, higher TNM stage, and lower histological differentiation grade were associated with poor MBC prognosis, and LMR, PLR, and NLR might be potential predictors for MBC prognosis.

Prognostic factors in atypical carcinoid tumors

Objectives: Carcinoid tumors are rare neuroendocrine neoplasms of the lung. Although typical and atypical carcinoids have different clinical courses, most studies in the literature evaluate them together. Therefore, we aimed to investigate prognostic factors in patients with atypical carcinoids, excluding typical carcinoids. Methods: We included 32 patients with atypical carcinoids according to WHO 2021 criteria admitted to Uludag University Hospital. We retrospectively extracted the clinicopathological characteristics from electronic medical records. The log-rank tests were used to determine the prognostic factors on survival. Results: Median age was 57 (24-71) years. Pathological stages were as follows: stage I in 41%, II in 9%, III in 34%, and IV in 16%. Median Ki-67 index was 11% (1-50). Median follow-up time was 46.2 (0.7-184.2) months. 12-month and 48-month disease-free survival (DFS) rates were 92.3% and 79.2%, respectively. 12-month and 48-month overall survival (OS) rates were 93.8% and 86.2, respectively. Receiver operating characteristic curve analysis determined the Ki-67 cut-off as 12.5%. The log-rank test indicated that Ki-67 and stage were statistically significant prognostic factors for DFS and OS. The patients with a Ki-67 index lower than 12.5% had longer DFS and OS (p = 0.007 and p = 0.020, respectively). Conclusions: The Ki-67 index and 8th TNM staging have prognostic value on DFS and OS in patients with atypical carcinoids. Large-scale studies are needed to define the optimal cut-off value of Ki-67.

Prognostic Factors of Non-epithelial Ovarian Cancer in a Tertiary Hospital in Indonesia

Introduction: Non-epithelial is a rare type of ovarian cancer but the most common ovarian neoplasm in reproductive age. This study analyzed the correlation of clinical characteristics to disease-free survival (DFS) and 3-year survival in non-epithelial ovarian cancer. Methods: A cohort analysis of medical records of 30 patients with non-epithelial ovarian cancer from 2016 to 2017 at Dr. Soetomo General Academic Hospital. Survival analysis was performed using Kaplan–Meier test, log-rank test, and Cox regression to determine the correlation of characteristics including age, stage, tumor size, tumor residue, histopathology type and chemotherapy status as prognostic factors for recurrence and mortality. Results: DFS was significantly affected by stage (p=0.049), tumor residue (p&lt;0.0001), and chemotherapy (p=0.005). Stage I, no residual disease, and adequate chemotherapy had the highest DFS and mean DFS rates (94.1% and 35.6 months; 95.5% and 35.7 months; 75% and 31.94 months, respectively). Highest recurrence rates were found in patients with unstaged disease (hazard ratio [HR]=10.08), residue &gt;0 cm (HR=23.13), and inadequate chemotherapy (HR=6.55). Three-year survival was significantly affected by stage (p=0.001), tumor residue (p&lt;0.0001), and chemotherapy (p&lt;0.0001). Stage I, no residual disease, and adequate chemotherapy had the highest 3-year survival rate and mean survival time (94.1% and 35.47 months; 95.5% and 35.7 months; 87.5% and 33 months). The highest mortality were found in patients with unstaged disease (HR=19.99), residue &gt;0 cm (HR=11.33), and inadequate chemotherapy (HR=11.71). Conclusion: Stage, tumor residue, and chemotherapy status in patients with non-epithelial ovarian cancer are significant prognostic factors for DFS and 3-year survival.

The usefulness of red blood cell distribution width and its ratio with platelet count in breast cancer after surgery and adjuvant treatment: a retrospective study.

To date, red blood cell distribution width (RDW) and RDW-to-platelet count ratio (RPR) have been investigated for their association with cancer. This study aimed to investigate the prognostic value of RDW and RPR in breast cancer before and after treatment. We retrospectively enrolled 395 patients with breast cancer, who were diagnosed between December 2009 and December 2015 and analyzed the association between RDW, RPR, and long-term prognosis. We also compared the RDW and RPR values with the pathologic parameters of breast cancer. The cutoff values for before-treatment RDW, RPR value, after-treatment RDW, and RPR were determined using receiver operating characteristic (ROC) curve analysis by identifying the highest Youden index. In the before-treatment state, no significant disease-free survival (DFS) or overall survival (OS) was found in the RPR and RDW values. However, we found that elevated after-treatment RPR and RDW were significant prognostic factors for DFS, with hazard ratios (HRs) of 2.233 [95% confidence interval (CI): 1.073-4.649; P=0.032] and 2.067 (95% CI: 1.085-3.937; P=0.027). Kaplan-Meier analysis indicated that the after-treatment RPR and RDW groups had poor OS (HR =30.461; 95% CI: 5.138-180.575; P<0.001) compared with the lower after-treatment RPR and RDW groups. In particular, when the RPR and RDW were in the lower group before the treatment and became elevated after the treatment, it showed a remarkably significant result for OS, with HR 132.6 (95% CI: 3.689-4,767.341; P=0.007) and 10.119 (95% CI: 1.853-55.249; P=0.008). Thus, after-treatment RPR and RDW could have prognostic value for breast cancer after surgery and adjuvant treatment.

Total Neoadjuvant Therapy for Rectal Cancer in the CAO/ARO/AIO-12 Randomized Phase 2 Trial: Early Surrogate Endpoints Revisited.

Simple SummaryMultimodal treatment of rectal cancer is undergoing dynamic change. In phase II/III multimodal rectal cancer trials, long-term survival remains the most objective endpoint for reporting treatment efficacy, but long follow-up is required, and there is a risk that the study results will lose scientific significance over time. To address these limitations, early surrogate endpoints are increasingly used to identify treatment efficacy at an earlier timepoint. We here report the prognostic role of pCR (pathological complete response), TRG (tumor regression grade) and NAR score (neoadjuvant rectal score) for DFS (disease-free survival) in the CAO/ARO/AIO-12 trial. Surrogate markers were significant prognostic factors for DFS, but the higher pCR rate und improved TRG in trial Arm B did not lead to improved survival compared to Arm A. Therefore, early surrogate marker correlated with clinical outcome in the CAO/ARO/AIO-12 trial, but the early differences in pCR and TRG did not translate into a survival benefit.Background: Early efficacy outcome measures in rectal cancer after total neoadjuvant treatment are increasingly investigated. We examined the prognostic role of pathological complete response (pCR), tumor regression grading (TRG) and neoadjuvant rectal (NAR) score for disease-free survival (DFS) in patients with rectal carcinoma treated within the CAO/ARO/AIO-12 randomized phase 2 trial. Methods: Distribution of pCR, TRG and NAR score was analyzed using the Pearson’s chi-squared test. Univariable analyses were performed using the log-rank test, stratified by treatment arm. Discrimination ability of non-pCR for DFS was assessed by analyzing the ROC curve as a function of time. Results: Of the 311 patients enrolled, 306 patients were evaluable (Arm A:156, Arm B:150). After a median follow-up of 43 months, the 3-year DFS was 73% in both groups (HR, 0.95, 95% CI, 0.63–1.45, p = 0.82). pCR tended to be higher in Arm B (17% vs. 25%, p = 0.086). In both treatment arms, pCR, TRG and NAR were significant prognostic factors for DFS, whereas survival in subgroups defined by pCR, TRG or NAR did not significantly differ between the treatment arms. The discrimination ability of non-pCR for DFS remained constant over time (C-Index 0.58) but was slightly better in Arm B (0.61 vs. 0.56). Conclusion: Although pCR, TRG and NAR were strong prognostic factors for DFS in the CAO/ARO/AIO-12 trial, their value in selecting one TNT approach over another could not be confirmed. Hence, the conclusion of a long-term survival benefit of one treatment arm based on early surrogate endpoints should be stated with caution.

The prognostic and predictive value of mismatch repair status in patients with locally advanced rectal cancer following neoadjuvant therapy

BackgroundWe examined the predictive value of mismatch repair (MMR) status in relation to responses to neoadjuvant therapy and the prognosis of locally advanced rectal cancer patients.MethodsA total of 854 consecutive patients with locally advanced rectal cancer with MMR status who underwent neoadjuvant therapy followed by curative surgery between January 2013 and December 2018 were included this retrospective study. MMR status was determined by an analysis of MMR protein expression by immunohistochemistry (IHC). Propensity score matching was performed to reduce imbalances in baseline characteristics. The categorical variables were compared using the Chi-square test or Fisher’s exact test. Local recurrence-free survival (LRFS) and disease-free survival (DFS) curves were estimated using the Kaplan-Meier method.ResultsDeficient MMR (dMMR) was detected in 63 of the 854 (7.4%) patients. Patients with dMMR had a lower proportion of tumor regression grade (TRG) of 0–1 compared with proficient MMR (pMMR) (28.6% vs. 43.7%; P=0.027). After propensity score matching at 1:4 for patients who received chemotherapy alone, proportion of TRG of 0–1 was observed to be significantly lower in dMMR than pMMR patients (9.1 vs. 30.3%%; P=0.013). For patients who received chemoradiation, after matching, no significant difference in the proportion of TRG 0–1 and the pathological complete response (pCR) rate was observed. The multivariable analysis revealed that patients whose tumors had dMMR had significantly longer DFS than those whose tumors had pMMR [hazards ratio (HR) =0.38, 95% confidence interval (CI): 0.18–0.81, P=0.013]. In the subgroup analysis, dMMR was only a statistically significant prognostic factor for DFS in patients with ypStage II/III (HR =0.38, 95% CI: 0.17–0.86; P=0.020).ConclusionsWe found that patients with dMMR responded worse to chemotherapy alone than patients with pMMR, in terms of TRG. Also, dMMR is a good prognostic marker for DFS in patients with ypStage II/III after neoadjuvant therapy.

The prognostic value of the lymph node ratio in patients with distal cholangiocarcinoma after curative intended surgery: A single-center retrospective study.

Backgrounds/AimsThe goal of the present study was to evaluate the prognostic value of lymph node ratio (LNR) in distal cholangiocarcinoma (DCC) after curative intended surgery.MethodsClinicopathological data of 162 DCC patients who underwent radical intended surgery between 2012 and 2020 were analyzed retrospectively. Prognostic factors related to overall survival (OS) and disease-free survival (DFS) were evaluated.ResultsMedian OS time and DFS time were 41 and 29 months, and 5-year OS rate and DFS rate were 44.7% and 38.1%, respectively. In the univariate analysis, significant prognostic factors for OS were histologic differentiation, American Joint Committee on Cancer (AJCC) stage, positive lymph node count, LNR, R1 resection, and perineural invasion. Preoperative carcinoembryonic antigen, carbohydrate antigen 19-9, infiltrative type, histologic differentiation, AJCC stage, positive lymph node count, LNR, R1 resection, perineural invasion, and lymph-vascular invasion were significant prognostic factors for DFS in the univariate analysis. In the multivariate analysis, histologic differentiation, R1 resection, and LNR were the independent prognostic factors for both OS and DFS. The LNR ≥ 0.2 group had a significantly poor prognosis in terms of OS (hazard ratio, 3.915; p = 0.002) and DFS (hazard ratio, 5.840; p < 0.001).ConclusionsLNR has significant value as a prognostic factor of DCC related to OS and DFS. LNR has the potential to be used as a modified staging system with furthermore studies.

Evaluation of prognostic factors after primary chemoradiotherapy of anal cancer: A multicenter study of the German Cancer Consortium-Radiation Oncology Group (DKTK-ROG)

Background and purposePrognosis after chemoradiotherapy (CRT) for anal squamous cell carcinoma (ASCC) shows marked differences among patients according to TNM subgroups, however individualized risk assessment tools to better stratify patients for treatment (de-) escalation or intensified follow-up are lacking in ASCC. Materials and methodsPatients’ data from eight sites of the German Cancer Consortium - Radiation Oncology Group (DKTK-ROG), comprising a total of 605 patients with ASCC, treated with standard definitive CRT with 5-FU/Mitomycin C or Capecitabine/Mitomycin C between 2004–2018, were used to evaluate prognostic factors based on Cox regression models for disease-free survival (DFS). Evaluated variables included age, gender, Karnofsky performance score (KPS), HIV-status, T-category, lymph node status and laboratory parameters. Multivariate cox models were separately constructed for the whole cohort and the subset of patients with early-stage (cT1-2 N0M0) tumors. ResultsAfter a median follow-up of 46 months, 3-year DFS for patients with early-stage ASCC was 84.9%, and 67.1% for patients with locally-advanced disease (HR 2.4, p < 0.001). T-category (HR vs. T1: T2 2.02; T3 2.11; T4 3.03), N-category (HR versus N0: 1.8 for N1-3), age (HR 1.02 per year), and KPS (HR 0.8 per step) were significant predictors for DFS in multivariate analysis in the entire cohort. The model performed with a C-index of 0.68. In cT1-2N0 patients, T-category (HR 2.14), HIV status (HR 2.57), age (1.026 per year), KPS (HR 0.7 per step) and elevated platelets (HR 1.3 per 100/nl) were associated with worse DFS (C-index of 0.7). ConclusionClassical clinicopathologic parameters like T-category, N-category, age and KPS remain to be significant prognostic factors for DFS in patients treated with contemporary CRT for ASCC. HIV and platelets were significantly associated with worse DFS in patients with early stage ASCC.

Long-term Outcomes of Liver Transplantation versus Resection for Hepatocellular Carcinoma: A Single-Center Experience

Introduction: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer deaths worldwide. Liver transplantation (LT) and liver resection (LR) are mainstay treatments for HCC. We compared the clinicopathologic features and long-term prognosis between patients receiving LT and LR for HCC. Methods: All patients who underwent LT or LR from 2010-2020 for HCC at a US transplant center were included. A total of 321 patients (137 LR, 184 LT) were enrolled. Overall survival (OS) and disease-free survival (DFS) were compared between LT and LR according to Milan criteria. Univariate and multivariable analyses including clinicopathologic factors were performed for both groups. Results: Significant differences in clinicopathologic factors existed between LT and LR groups; LT patients were more likely to be male, Caucasian, have higher MELD, cirrhosis, and be within Milan criteria. The OS rates at 1/5/7 years for LT and LR groups were 94.0%/77.5%/71.1% vs 79.3%/48.3%/38.5%, respectively (p <0.001). The DFS rates at 1/5/7 years for LT and LR groups were 98.2%/84.6%/84.6% vs. 71.9%/42.5%/24.8%, respectively (p <0.001). For patients beyond Milan criteria, LT group showed significantly better OS rate compared to LR group (p=0.002). Regarding DFS rates, LT groups showed significantly better survival compared to LR both within and beyond Milan criteria (p <0.001). In multivariable analysis, Milan criteria was the only significant prognostic factor for DFS in both groups (HR 31.29 LT, p=0.039; HR 4.516 LR, p=0.020). Conclusions: Liver transplantation is associated with better long-term clinical outcomes than liver resection for the treatment of HCC.

Clinicopathological Characteristics and Disease-Free Survival in Patients with Hürthle Cell Carcinoma: A Multicenter Cohort Study in South Korea.

Background Hürthle cell carcinoma (HCC), a type of thyroid carcinoma, is rare in South Korea, and few studies have investigated its prognosis.Methods This long-term multicenter retrospective cohort study evaluated the clinicopathological features and clinical outcomes in patients with HCC who underwent thyroid surgery between 1996 and 2009.Results The mean age of the 97 patients included in the study was 50.3 years, and 26.8% were male. The mean size of the primary tumor was 3.2±1.8 cm, and three (3.1%) patients had distant metastasis at initial diagnosis. Ultrasonographic findings were available for 73 patients; the number of nodules with low-, intermediate-, and high suspicion was 28 (38.4%), 27 (37.0%), and 18 (24.7%), respectively, based on the Korean-Thyroid Imaging Reporting and Data System. Preoperatively, follicular neoplasm (FN) or suspicion for FN accounted for 65.2% of the cases according to the Bethesda category, and 13% had malignancy or suspicious for malignancy. During a median follow-up of 8.5 years, eight (8.2%) patients had persistent/recurrent disease, and none died of HCC. Older age, gross extrathyroidal extension (ETE), and widely invasive types of tumors were significantly associated with distant metastasis (all P<0.01). Gross ETE (hazard ratio [HR], 27.7; 95% confidence interval [CI], 2.2 to 346.4; P=0.01) and widely invasive classification (HR, 6.5; 95% CI, 1.1 to 39.4; P=0.04) were independent risk factors for poor disease-free survival (DFS).Conclusion The long-term prognosis of HCC is relatively favorable in South Korea from this study, although this is not a nation-wide data, and gross ETE and widely invasive cancer are significant prognostic factors for DFS. The diagnosis of HCC by ultrasonography and cytopathology remains challenging.

Prognostic Factors for Survival in Transverse Colon Cancers.

Transverse colon cancer (TCC) is a rare condition that accounts for 10% of all colon cancers. TCC was accepted more likely right-sided colon cancers. We aimed to investigate whether TCC differs from other colon tumors by using clinical, pathological, and molecular prognostic factors known to be important in colon cancer and if it differs in its own anatomical structure. We evaluated local and locally advanced TCC patients between 2007 and 2020years for demographics data, symptoms, treatment status, and histopathological and molecular features. Overall, 107 TCC patients were included in this study. According to the molecular data analysis of 44, 35, and 23 patients for MSI, RAS, and BRAF status, respectively, 7 (15.9%) were MSI-H, 13 (37.1%) were RAS mutant, and 11 (47.8%) had BRAF V600E mutation. The median follow-up time was 31.5months. Median disease-free survival (DFS) was 5.19months, and median OS was 88.3months for the whole study population. The tumor stage was the most significant prognostic factor for DFS and OS. Although BRAF mutation was not a significant marker for DFS, it was an independent prognostic marker for OS (HR 3.90 95% CI 1.42-10.7). There were no statistically significant differences between proximal two-thirds and distal one-third tumor location. TCC has molecular features and prognostic factors more likely RCC and no differences between proximal and distal sub-parts. BRAF V600E mutation status is an independent predictor of survival even in the early stages of TCC.

Stool elastase as an independent prognostic factor in patients with pancreatic head cancer

In pancreatic cancer, pancreatic exocrine insufficiency (PEI) is found in 44.5%, is more common in pancreatic head cancer. Patients with PEI have an increased risk of malnutrition, which in turn increases morbidity and mortality. The aim of this study was to analyze the prognosis according to the PEI measured by Stool elastase (SE) level in patients with pancreatic head cancer. Patients who underwent pancreaticoduodenectomy due to pancreatic cancer at Seoul National University Hospital from 2011 to 2015 were included. Among these patients, the patients who had the preoperative SE level were analyzed. Groups were classified based on 100 µg/g, which can be defined as severe PEI. Total 143 patients were included. Median preoperative stool elastase level was 67.2 µg/g. 84 patients (58.7%) were in the low SE group and 59 patients (41.3%) were in the high SE group. There were no significant difference in R0 resection rate, final pathologic stages and adjuvant treatment between the two groups. The two groups had significantly different overall survival (OS) and disease-free survival (DFS), and low SE group had a worse prognosis (median OS: 17 versus 25 months, p = 0.035, median DFS: 8 versus 14 months, p = 0.006). On multivariate analysis, stool elastase ≥ 100 µg/g (hazard ratio (HR): 1.487, p = 0.048), and no lymph node metastasis (HR: 1.852, p = 0.005) were found to be independent prognostic factors for better OS. And those were also significant prognostic factor for DFS. PEI measured by SE level is an independent prognostic factor for patients with pancreatic head cancer who undergoing pancreaticoduodenectomy. In these patients, management of severe PEI such as nutritional support is expected to be required.

Prognostic Factors Affecting Disease-Free Survival and Overall Survival in T4 Colon Cancer.

PurposeIt is known that as the T stage of a carcinoma progresses, the prognosis becomes poorer. However, there are few studies about factors that affect the prognosis of T4 advanced colon cancer. This study aimed to identify the prognostic factors associated with disease-free survival (DFS) and overall survival (OS) in T4 colon cancer.MethodsPatients diagnosed with stage T4 on histopathology after undergoing curative surgery for colon cancer between March 2009 and March 2018 were retrospectively analyzed for factors related to postoperative survival. Primary outcomes were DFS and OS.ResultsEighty-two patients were included in the study. DFS and OS of the pathologic (p) T4b group were not inferior to that of the pT4a group. Multivariate analysis showed that differentiation (hazard ratio [HR], 4.994; P = 0.005), and laparoscopic surgery (HR, 0.323; P = 0.008) were significant prognostic factors for DFS, while differentiation (HR, 7.904; P ≤ 0.001) and chemotherapy (HR, 0.344; P = 0.038) were significant prognostic factors for OS.ConclusionTumor differentiation, laparoscopic surgery, and adjuvant chemotherapy were found to be significant prognostic factors in patients with T4 colon cancer. Adjuvant chemotherapy and curative resections by laparoscopy might improve the prognosis in these patients.

Noninvasive evaluation of tumor immune microenvironment in patients with clear cell renal cell carcinoma using metabolic parameter from preoperative 2-[18F]FDG PET/CT.

Nowadays, it is necessary to explore effective biomarkers associated with tumor immune microenvironment (TIME) noninvasively. Here, we investigated whether the metabolic parameter from preoperative 2-[18F]FDG PET/CT could provide information related to TIME in patients with clear cell renal cell carcinoma (ccRCC). Ninety patients with newly diagnosed ccRCC who underwent 2-[18F]FDG PET/CT prior to surgery were retrospectively reviewed. The immunological features included tumor-infiltrating lymphocytes (TILs) density, programmed death-ligand 1 (PD-L1) expression, and tumor immune microenvironment types (TIMTs). TIMTs were classified as TIMT I (positive PD-L1 and high TILs), TIMT II (negative PD-L1 and low TILs), TIMT III (positive PD-L1 and low TILs), and TIMT IV (negative PD-L1 and high TILs). The relationship between maximum standardized uptake value (SUVmax) in the primary lesion from 2-[18F]FDG PET/CT and immunological features was analyzed. Cox proportional hazards analyses were performed to identify the prognostic factors for disease-free survival (DFS) after nephrectomy. Tumors with high TILs infiltration showed remarkable correlation with elevated SUVmax and aggressive clinicopathological characteristics, such as high World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade. PD-L1 expression on tumor cells was positively associated with WHO/ISUP grade and negatively correlated with body mass index (BMI). However, no correlation was observed between SUVmax and PD-L1 expression, regardless of its spatial tissue distribution. SUVmax of TIMT I and IV was higher than that of TIMT II, but there was remarkable difference merely between TIMT II and IV. In multivariate analysis, SUVmax (P = 0.022, HR 3.120, 95% CI 1.175-8.284) and WHO/ISUP grade (P = 0.046, HR 2.613, 95% CI 1.017-6.710) were the significant prognostic factors for DFS. Six cases (16.2%) with normal SUVmax showed disease progression, while 25 cases (71.4%) with elevated SUVmax experienced disease progression. Conversely, the immunological features held no prognostic value. Our findings demonstrated that 2-[18F]FDG PET/CT could provide metabolic information of TIME for ccRCC patients and develop image-guided therapeutic strategies accordingly. Patients with elevated preoperative SUVmax should be seriously considered, and perioperative immunotherapy might be beneficial for them.

Role in staging and prognostic value of pretherapeutic F-18 FDG PET/CT in patients with gastric MALT lymphoma without high-grade transformation

The purpose of this retrospective study was to investigate the role in staging and prognostic value of pretherapeutic fluorine-18-fluorodeoxyglucose (F-18 FDG) positron emission tomography (PET)/computed tomography (CT) in patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma without high-grade transformation (HT). We retrospectively reviewed 115 consecutive patients with histopathologically confirmed gastric MALT lymphoma without HT who underwent pretherapeutic F-18 FDG PET/CT. Kaplan–Meier and Cox proportional-hazards regression analyses were used to identify independent prognostic factors for disease free survival (DFS) among 13 clinical parameters and three PET parameters. In two of 115 patients (1.7%), the clinical stage appeared higher according to F-18 FDG PET/CT. In univariate analysis, Helicobacter pylori (HP) infection (P = 0.023), treatment modality (P < 0.001), and stage including PET/CT (P = 0.015) were significant prognostic factors for DFS. In multivariate analysis, only treatment modality was an independent prognostic factor (P = 0.003). In conclusion, F-18 FDG PET/CT played an important role in enabling upstaging of patients with gastric MALT lymphoma without HT. F-18 FDG PET/CT may have a prognostic role in gastric MALT lymphoma without HT by contributing to better staging.

Pseudohypoxic pheochromocytomas and paragangliomas dominate in children.

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that are associated with cancer predisposition syndromes in up to 80% of affected children. PPGLs can be divided into molecularly defined groups with comparable pathogenesis and biology: (1) pseudohypoxic, (2) kinase signaling, and (3) Wnt-altered. We report the data of children and adolescents diagnosed with PPGL who have been registered with the German GPOH-MET registry since 1997. By December 2019, a total of 88 patients with PPGL were reported. Pheochromocytoma occurred in 56%, paraganglioma in 35%, and synchronous PPGLs in 9.1%. A total of 16% of patients presented with lymph node (5.7%) and distant metastases (10%). Median follow-up was 4.2years (range 0-17.1). Overall and disease-free survival (DFS) were 98.6% and 54.0%, respectively. Local relapses, metastases, and subsequent PPGLs occurred in 11%, 4.5%, and 15% of patients. Germline mutations were detected in 83% of patients (51% in VHL, 21% in SDHB, 7.8% in SDHD, and one patient each in RET and NF1). One patient was diagnosed with Pacak-Zhuang syndrome. A total of 96% of patients presented with PPGL of the pseudohypoxic subgroup (34% TCA cycle-related, 66% VHL/EPAS1-related). In multivariate analyses, extent of tumor resection was a significant prognostic factor for DFS. Most pediatric PPGLs belong to the pseudohypoxia subgroup, which is associated with a high risk of subsequent PPGL events and metastatic disease. Comprehensive molecular profiling of children and adolescents with newly diagnosed PPGLs will open new avenues for personalized diagnosis, treatment, and surveillance.

The Change of Systemic Immune-Inflammation Index Independently Predicts Survival of Colorectal Cancer Patients after Curative Resection.

Background The systemic immune-inflammation index (SII) has an important role in predicting survival in some solid tumors. However, little information is available concerning the change of the SII (∆SII) in colorectal cancer (CRC) after curative resection. This study was designed to evaluate the role of ∆SII in CRC patients who received surgery. Methods A total 206 patients were enrolled in this study. Clinicopathologic characteristics and survival were assessed. The relationships between overall survival (OS), disease-free survival (DFS), and ∆SII were analyzed with both univariate Kaplan-Meier and multivariate Cox regression methods. Results Based on the patient data, the receiver operating characteristic (ROC) optimal cutoff value of ∆SII was 127.7 for OS prediction. The 3-year and 5-year OS rates, respectively, were 60.4% and 36.7% in the high-∆SII group (>127.7) and 87.6% and 79.8% in the low-∆SII group (≤127.7). The 3-year and 5-year DFS rates, respectively, were 54.1% and 34.1% in the high-∆SII group and 80.3% and 78.5% in the low-∆SII group. In the univariate analysis, smoking, pathological stages III-IV, high-middle degree of differentiation, lymphatic invasion, vascular invasion, and the high-ΔSII group were associated with poor OS. Adjuvant therapy, pathological stages III-IV, vascular invasion, and ΔSII were able to predict DFS. Multivariate analysis revealed that pathological stages III-IV (HR = 0.442, 95% CI = 0.236-0.827, p = 0.011), vascular invasion (HR = 2.182, 95% CI = 1.243-3.829, p = 0.007), and the high-ΔSII group (HR = 4.301, 95% CI = 2.517-7.350, p < 0.001) were independent predictors for OS. Adjuvant therapy (HR = 0.415, 95% CI = 0.250-0.687, p = 0.001), vascular invasion (HR = 3.305, 95% CI = 1.944-5.620, p < 0.001), and the high-ΔSII group (HR = 4.924, 95% CI = 2.992-8.102, p < 0.001) were significant prognostic factors for DFS. Conclusions The present study demonstrated that ∆SII was associated with the clinical outcome in CRC patients undergoing curative resection, supporting the role of ∆SII as a prognostic biomarker.

Surgical Resection versus Re-Ablation for Intrahepatic Recurrent Hepatocellular Carcinoma after Initial Ablation Therapy

Background and Aims: Whether surgical resection or repeated ablation should be recommended for intrahepatic recurrent hepatocellular carcinoma (HCC) conforming to the Milan criteria after initial ablation remains unclear. In this study, we compared the outcomes of patients who underwent surgical resection with those who underwent re-ablation for recurrent HCC after initial curative-intent ablation. Methods: The data of 28 and 98 patients who underwent surgical resection and re-ablation, respectively, for recurrent HCC after initial ablation between January 2003 and 2017 were analyzed using propensity score matching. Results: Before matching, the 1-, 3-, and 5-year overall survival (OS) rates were 95.7, 83.0, and 74.4% for the ablation group, compared to 92.9, 89.1, and 70.9% for the resection group (p = 0.490). The corresponding disease-free survival (DFS) rates were 67.5, 40.1, and 25.6% for the ablation group and were 85.4, 59.9, and 53.3% for the resection group (p = 0.018). After matching, the 1-, 3-, and 5-year OS rates for the ablation and resection group were 95.2, 85.5 and 81.8% versus 96.0, 96.0, and 76.4%, respectively (p = 0.550). The 1-, 3-, and 5-year DFS rates were 58.0, 39.5, and 29.9% for the ablation group and were 95.8, 67.2, and 59.8% for the resection group (p = 0.004). Cox proportional hazards model identified surgical resection as the only significant prognostic factor for DFS but not for OS. Conclusion: For intrahepatic recurrent HCC patients after initial ablation, surgical resection could provide better DFS than re-ablation, while no difference in OS was observed between the 2 treatment groups.

Impact of sidedness of colorectal cancer on tumor immunity

BackgroundClinical and molecular characteristics differ between right-sided and left-sided colorectal cancer (CRC). This study aimed to clarify the correlation between CRC sidedness and tumor immunity.MethodsA total of 102 patients who underwent curative colectomy for stage II/III CRC were included in this study. The expression of programmed cell death (PD)-1, PD1-ligand 1 (PD-L1), forkhead box P3 (Foxp3), transforming growth factor (TGF)-β, and indoleamine-pyrrole 2,3-dioxygenase (IDO) were examined using immunohistochemistry and the relationships between sidedness and several prognostic factors were examined.ResultsClinicopathological factors were not significantly different between right- and left-sided CRC. The tumor immunity-related molecule PD-L1 was more highly expressed in right-sided than in left-sided CRC (62.9% vs. 30.6%, p<0.01). No significant difference was found in overall survival (OS) and disease-free survival (DFS) by sidedness. PD-1 and Foxp3 expression were significant prognostic factors for OS. Lymph node metastasis (N), lymphatic invasion (ly), and PD-L1 expression were significant prognostic factors for DFS. In right-sided CRC, IDO-positive patients had a poor OS (p<0.05), and IDO was the only independent prognostic indicator for OS. N and venous invasion were identified as independent prognostic indicators for DFS. In left-sided CRC, univariate analysis identified PD-1, PD-L1, and Foxp3 expression as significant predictors of poor OS. Multivariate analysis confirmed PD-L1 expression as an independent prognostic indicator. N, ly, and PD-L1 expression levels were identified as significant predictors of poor DFS.ConclusionsThe prognostic factors were IDO in right-sided CRC and PD-L1 and Foxp3 in left-sided CRC. These findings indicated that tumor immunity might play different roles depending upon sidedness. Tumor location may be an important factor to consider when assessing immune response and therapeutic decisions in CRC patients.

Evaluation of Prognostic Factors for Survival in Transverse Colon Cancer.

Simple SummaryTransverse colon cancer (TCC) is mostly included among right-sided colon cancer, and sometimes even excluded at all, thus it is not completely clear if they present total similarities with right-sided ones or if they have their own specific features. With a median follow-up of 34 months, we concluded that TCC shares some clinicopathological characteristics with left-sided colon cancer and many others with the right-sided ones, but only poorly/undifferentiated tumor grade and BRAF V600E mutation are independent prognostic factors for survival, regardless of tumor stage. The present study provides more insightful knowledge of clinicopathological characteristics of TCC patients, emphasize the role of BRAF mutation since the early stage of disease and lay the basis for new treatment algorithms in this specific setting of colon cancer.Background: Although most of the analyses included transverse colon cancers (TCC) among right colon cancer (RCC), it is not completely clear if they present total similarities with RCC or if they have their specific features. Therefore, we present an observational study to evaluate clinicopathological characteristics and survival data of patients with TCC. Methods: We retrospectively reviewed 450 RCC, of whom 97 stages I–IV TCC were included in this multicenter study; clinicopathological and molecular parameters were analyzed to identify prognostic factors for disease-free survival (DFS) and overall survival (OS). Results: Most of TCC cases were male (61%), with ≤70 years old (62%), and good performance status (ECOG PS 0, 68%). According to WHO classification, 41 (49%) and 40 (48%) tumors were classified as well to moderate and poorly/undifferentiated respectively, regardless of mucinous component (30%). About molecular data, 8 (26%), 45 (63%), and 14 (24%) were MSI-H, KRAS wild-type, and BRAF V600E mutant, respectively. With a median follow-up of 34 months, there were 29 and 50 disease recurrences and deaths respectively. Charlson comorbidity index ≥5 was a significant prognostic factor for DFS (HR = 7.67, 95% CI 2.27–25.92). Colon obstruction/perforation (HR = 2.65, 95% CI 1.01–7.01), and BRAF mutant (HR = 3.03, 95% CI 0.97–9.50) cases showed a worst, despite not statistically significant, DFS. Whereas for OS, at the multivariate model, only tumor grade differentiation (HR = 5.26, 95% CI 1.98–14.01) and BRAF mutation status (3.71, 95% CI 1.07–12.89) were independent prognostic factors. Conclusions: Poorly/undifferentiated tumor grade and BRAF V600E mutation are independent prognostic factors for OS in TCC. Further prospective clinical trials are needed to better define TCC treatment in order to improve patient outcome.