Central hepatectomy versus major hepatectomy for patients with centrally located hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND AND AIM: For those with a centrally located HCC, the two types of liver sectionectomy that can be performed are extended hepatectomy (EH) and central hepatectomy (CH). This meta-analysis aimed to compare the short- and long-term outcomes between patients treated with CH and patients treated with EH for those with centrally located HCC. METHOD: We searched PubMed, Scopus, Web of Science, and Cochrane library for eligible studies from inception to 1 April 2022 and a systematic review and meta-analysis were done to compare the outcomes between the two groups. RESULTS: we included 9 studies with a total of 1674 patients in this study. The pooled results in this meta-analysis showed equal long-term overall survival, Disease-free survival, recurrence and mortality between the two groups (5-year OS, RR = 1.14, 95% CI = 0.96-1.35, P = 0.12; I2 = 56%), (5-year DFS, RR = 0.81, 95% CI = 0.61-1.08, P = 0.15; I2 = 60%), (Recurrence, RR = 1.04, 95% CI = 0.94-1.15, P = 0.45; I2 = 27%), and (Mortality, RR = 0.55, 95% CI = 0.26-1.15, P = 0.11; I2 = 0%). In addition to that, no significant difference could be detected in the overall incidence of complications between the two groups (Complications, RR = 0.94, 95% CI = 0.76-1.16, P = 0.57; I2 = 0%). However, CH is associated with a remarkable increase in the rate of biliary fistula (Biliary fistula, RR = 1.90, 95% CI = 1.07-3.40, P = 0.03; I2 = 0%). And Liver cell failure was higher in the case of EH (LCF, RR = 0.47, 95% CI = 0.30-0.76, P = 0.002; I2 = 0%). Regarding the operative details, CH is associated with longer operative time (Time of the operation, Mean difference = 0.82, 95% CI = 0.36, 1.27, P = 0.0004; I2 = 57%). CONCLUSION: No significant difference in the short and long-term survival and recurrence between CH and MH for CL-HCC. However, CH is associated with greater future remnant liver volume that decreases the incidence of LCF and provides more opportunities for a repeat hepatectomy after tumour recurrence.

Long-Term Outcomes of Laparoscopic Liver Resection for Centrally Located Hepatocellular Carcinoma.

Background and Objectives: The feasibility of laparoscopic liver resection (LLR) for centrally located hepatocellular carcinoma (cHCC 1 cm of the hilum, major hepatic veins, and inferior vena cava) is still controversial. This study aims to evaluate the feasibility and safety of LLR for cHCC and compare the perioperative outcomes with those of open liver resection (OLR). Materials and Methods: This retrospective study included 110 patients who underwent LLR (n = 59) or open liver resection (OLR) (n = 51) for cHCC between January 2004 and September 2018. LLR group was divided into the following two subgroups according to the date of operation: Group 1 (n = 19) and Group 2 (n = 40), to account for the advancement in the laparoscopic techniques. Results: No mortality within 3 months was observed. There were no significant differences in operation time (285 vs. 280 min; p = 0.938) and postoperative complication rate (22.0% vs. 27.5%; p = 0.510) between both groups. However, intraoperative blood loss (500 vs. 700 mL; p < 0.001), transfusion rate (10.2% vs. 31.4%; p = 0.006), and hospital stay (6 vs. 10 days; p < 0.001) were significantly lower in the LLR group than in the OLR group. In the LLR group, Group 2, showed a shorter hospital stay than Group 1 (6 vs. 8 days; p = 0.006). There were improvements in the operation time (280 vs. 360 min; p = 0.036) and less intraoperative blood loss (455 vs. 500 mL; p = 0.075) in Group 2. Conclusions: We demonstrated that LLR can be safely performed in highly selected patients with cHCC.

Development and clinical validation of a robust knowledge-based planning model for stereotactic body radiotherapy treatment of centrally located lung tumors.

PURPOSE: To develop a robust and adaptable knowledge-based planning (KBP) model with commercially available RapidPlanTM for early stage, centrally located non-small-cell lung tumors (NSCLC) treated with stereotactic body radiotherapy (SBRT) and improve a patient's"simulation to treatment" time. METHODS: The KBP model was trained using 86 clinically treated high-quality non-coplanar volumetric modulated arc therapy (n-VMAT) lung SBRT plans with delivered prescriptions of 50 or 55 Gy in 5 fractions. Another 20 independent clinical n-VMAT plans were used for validation of the model. KBP and n-VMAT plans were compared via Radiation Therapy Oncology Group (RTOG)-0813 protocol compliance criteria for conformity (CI), gradient index (GI), maximal dose 2 cm away from the target in any direction (D2cm), dose to organs-at-risk (OAR), treatment delivery efficiency, and accuracy. KBP plans were re-optimized with larger calculation grid size (CGS) of 2.5 mm to assess feasibility of rapid adaptive re-planning. RESULTS: Knowledge-based plans were similar or better than n-VMAT plans based on a range of target coverage and OAR metrics. Planning target volume (PTV) for validation cases was 30.5 ± 19.1 cc (range 7.0-71.7 cc). KBPs provided an average CI of 1.04 ± 0.04 (0.97-1.11) vs. n-VMAT plan'saverage CI of 1.01 ± 0.04 (0.97-1.17) (P < 0.05) with slightly improved GI with KBPs (P < 0.05). D2cm was similar between the KBPs and n-VMAT plans. KBPs provided lower lung V10Gy (P = 0.003), V20Gy (P = 0.007), and mean lung dose (P < 0.001). KBPs had overall better sparing of OAR at the minimal increased of average total monitor units and beam-on time by 460 (P < 0.05) and 19.2 s, respectively. Quality assurance phantom measurement showed similar treatment delivery accuracy. Utilizing a CGS of 2.5 mm in the final optimization improved planning time (mean, 5 min) with minimal or no cost to the plan quality. CONCLUSION: The RTOG-compliant adaptable RapidPlan model for early stage SBRT treatment of centrally located lung tumors was developed. All plans met RTOG dosimetric requirements in less than 30 min of planning time, potentially offering shorter "simulation to treatment" times. OAR sparing via KBPs may permit tumorcidal dose escalation with minimal penalties. Same day adaptive re-planning is plausible with a 2.5-mm CGS optimizer setting.

[Three-dimensional visual assessment and virtual reality study of centrally located hepatocellular carcinoma on the axis of blood vessels].

Objective: To explore a novel method for preoperative precision assessment of centrally located hepatocellular carcinoma(HCC) with blood vessel as axis based on three-dimensional(3D) visualization and virtual reality(VR) technology and its application values. Methods: High-quality thin-layer enhanced CT data were collected from 20 patients with centrally located HCC who treated at First Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University from March 2017 to August 2018 diagnosed by preoperative examination. There were 18 males and 2 females, aged 28 to 69 years, all of Child-Pugh grade A. First of all, 3D reconstruction was performed by a 3D visualization software; then, the reconstructed 3D image was imported into VR development engine for VR research; afterwards, the analysis and evaluation system with blood vessel as axis was established based on 3D visualization classification of centrally located HCC; therefore, the relationship of the tumor to its major peripheral blood vessels was accurately judged and the surgical planning was formulated. Two images were brought into the operating room for navigation in surgery. The assessments results of preoperative data (CT and (or) MRI) and three-dimensional visualization of blood vessels in VR environment were compared; the values of the preoperative and postoperative hemoglobin, serum albumin and bilirubin were recorded and compared. Chi-square test, t-test and non-parametric test were used for the analysis of counting data, continuous measurement data and non-normal distribution measurement data, respectively. Results: 3D visualization modeling was completed in all of the 20 patients with centrally located HCC. According to the results of 3D visualization classification of centrally located HCC, there were 3 cases of type Ⅰ,1 case of type Ⅱ,4 cases of type Ⅲ,7 cases of type Ⅳ and 5 cases of type Ⅴ; according to the assessment and classification based on blood vessel as the axis, there were 6 cases of type Ⅰa,2 cases of type Ⅰb,2 cases of type Ⅱa,9 cases of type Ⅱb and 1 case of type Ⅱc. All patients underwent successful resection of tumor under the guidance of 3D visualization and VR technology. There were 15 cases whose assessment results based on preoperative CT/MRI were consistent with intraoperative findings, with a coincidence rate of 75.0%(15/20); while in VR environment, the assessment results of 3D visualization with blood vessel as axis were all consistent with the intraoperative findings, with coincidence rate of 100%(20/20). There was a statistically significant difference between the groups (χ(2)=5.714, P=0.017). There was no red blood cell transfusion in all patients during the operation. The preoperative hemoglobin was (128.8±14.9)g/L, and it was (119.8±12.5)g/L on postoperative day 1. There was no significant difference between these two sets of data (t=2.07, P=0.054). No death during the perioperative period and no complications such as hepatic failure, hemorrhage and biliary fistula after operation occurred. Conclusion: Preoperative evaluation based on 3D visualization and VR technology with blood vessel as the axis has significant clinical value for preoperative planning and surgical navigation of centrally located HCC.

Phase I study of stereotactic body radiation therapy for centrally located stage IA non-small cell lung cancer (JROSG10-1).

BACKGROUND: To investigate the maximum tolerated dose (MTD) and recommended dose (RD) of stereotactic body radiation therapy (SBRT) for centrally located stage IA non-small cell lung cancer (NSCLC). METHODS: Five dose levels, ranging from of 52 to 68 Gy in eight fractions, were determined; the treatment protocol began at 60 Gy (level 3). Each dose level included 10 patients. Levels 1-2 were indicated if more than four patients exhibited dose-limiting toxicity (DLT), which was defined as an occurrence of a grade 3 (or worse) adverse effect within 12 months after SBRT initiation. MTD was defined as the lowest dose level at which more than four patients exhibited DLT. RESULTS: Ten patients were enrolled in the level 3 study. One patient was considered unsuitable because of severe emphysema. Therefore, nine patients were evaluated and no patient exhibited DLT. The level 3 results indicated that we should proceed to level 4 (64 Gy). However, due to the difficulty involved in meeting the dose constraints, further dose escalation was not feasible and the MTD was found to be 60 Gy. CONCLUSIONS: The RD of SBRT for centrally located stage IA NSCLC was 60 Gy in eight fractions.

[A prospective pilot study of combined intra-operative radiotherapy for centrally located hepatocellular carcinomas].

Objective: To carry out a prospective cohort study of combined intra-operative radiotherapy for centrally located hepatocellular carcinomas (HCC) and to observe the safety and postoperative complications. Methods: A total of 79 patients with centrally located HCC who underwent hepatectomy were divided into two groups: experimental group (combined with targeted intra-operative radiotherapy, 32 cases) and control group (single surgical operation, 47 cases). Patients in the experimental group received intra-operative electron radiotherapy after tumor resection, while patients in the control group received to intra-operative electron radiotherapy.The haemorrhagia amount and operation time during the operation, intra-operative liver function and the recovery of liver and gastrointestinal tract of patients in these two groups were compared. Results: No postoperative 30-day mortality was observed in all of the patients. The average total operation time of patients in the experimental group was (319±76) min, significantly longer than (233±76) min of the control group (P<0.001). The average aspartate transaminase (AST) level of patients in the experimental group at postoperative day 1 was 562.5 U/L, significantly higher than 347.0 U/L of control group (P=0.031). However, the average prothrombin activity levels of patients in the experimental group at postoperative day 3 and day 7 were (68.3±17.9)% and (73.4±10.2)%, respectively, significantly lower than (78.9±15.9)% and (80.0±10.6)% of control group (both P<0.05). There were no significant differences of tumor volume, differentiation degree, satellite lesion, dorsal membrane invasion, microvascular invasion between these two groups (all P>0.05). There were no significant differences of hospital stay, ventilation time, the incidence of hepatic insufficiency, ascites, pleural effusion, infection, biliary fistula between these two groups (all P>0.05). There were no significant differences of alanine aminotransferase (ALT), albumin, total bilirubin between these two groups at postoperative day 1, 3, 5 and 7 (all of P>0.05). Conclusion: The resection of centrally located HCC combined with intra-operative radiotherapy may increase the total operation time, delay the early postoperative recovery of liver function, but it is still safe and feasible. Trial registration: National Cancer Centre /Cancer Hospital, Chinese Academy of Medical Sciences, ChiCTR-TRC-12002802.

Long-term outcomes of PDT for centrally-located early lung cancers with tumor diameters > 2.0 cm.

BACKGROUND: Photodynamic therapy (PDT) is used for the treatment of centrally-located early lung cancers (CLELCs) and is recommended for tumors ≤ 1.0 cm in diameter. We previously reported that PDT using talaporfin sodium, second-generation photosensitizer, for tumors > 1.0 cm but ≤ 2.0 cm in diameter was able to achieve a therapeutic outcome comparable to that of tumors with a diameter of ≤ 1.0 cm. However, the effectiveness of PDT using talaporfin sodium for tumors > 2.0 cm in diameter remains unclear. We conducted a retrospective analysis of cases in which PDT was performed for flat-type CLELCs with tumor diameters of > 2.0 cm. METHODS: We retrospectively analyzed seven cases (eight lesions) with tumor diameters > 2.0 cm and no evidence of extracartilaginous invasion or lymph node metastasis. RESULTS: All the patients underwent multiple PDT sessions. The PDT treatment results over the study period were partial response in one case (14.3 %), stable disease (SD) in three cases (42.9 %), and progressive disease (PD) in three cases (42.9 %). At the time of writing this report, five of seven cases (71.4 %) are still undergoing treatment. The duration of SD-the time from the start of treatment until the criteria for PD were met (SD or better maintained)-ranged from 7 to 52 months (mean, 25.3 months). CONCLUSIONS: "Maintenance PDT" for CLELCs > 2.0 cm in diameter has the potential to inhibit tumor progression in the long term while maintaining quality of life, rather than simply aiming only for a quick radical cure.

Long-term outcome of adjuvant radiotherapy upon postoperative relapse of centrally located hepatocellular carcinoma: a real-world study.

Despite that surgical resection is widely regarded as the most effective approach to the treatment of liver cancer, its safety and efficacy upon centrally located hepatocellular carcinoma (HCC) remain unsatisfactory. In consequence, seeking an integrated treatment, like combined with adjuvant radiotherapy, to enhance the prognosis of patients is of critical importance. By recruiting patients undergoing surgical resection for centrally located HCC ranging from June 2015 to 2020, they were divided into liver resection combined with adjuvant radiotherapy (LR + RT) and mere liver resection (LR) groups. The calculation of propensity score and model of Cox proportional hazards regression were utilized. 193 patients were recruited in aggregation, containing 88 ones undergoing LR + RT, while 105 handled with LR. RT was verified to be an independent factor of prognosis for relapse (HR 0.60). In propensity-score analyses, significant association existed between adjuvant radiotherapy and better disease-free survival (DFS) (Matched, HR 0.60; Adjustment of propensity score, HR 0.60; Inverse probability weighting, HR 0.63). The difference of DFS was apparent within two groups (p value = 0.022), and RT significantly down-regulated early relapse (p value < 0.05) in subgroup analysis. The calculation of E-value revealed robustness of unmeasured confounding. The combination of liver surgical resection with RT is safe and effective towards patients with centrally located HCC, which would notably enhance the prognosis and decrease the early relapse of HCC.

Long-term outcome of centrally located hepatocellular carcinoma treated by neoadjuvant radiotherapy and radical resection: a propensity score matched study.

Objective: Centrally located hepatocellular carcinoma (HCC) typically presents challenges in surgical intervention and is associated with a bleak prognosis. In order to address this pressing issue, it is imperative to identify a comprehensive treatment approach, such as neoadjuvant radiotherapy (neoRT), that can enhance the prognosis of patients diagnosed with centrally located HCC. Methods: Patients who had surgical resections for HCC between March 2015 and December 2020 were included in the study. Patients were assigned to either the neoRT combined with liver resection (neoRT+LR) group or the liver resection alone (LR) group. The study employed propensity-score analysis and Cox proportional-hazards regression models as research methodologies. Using the Kaplan-Meier method, overall survival (OS) and disease-free survival (DFS) were estimated in patients. Results: During the study, 162 patients were enrolled, with 41 receiving neoRT+LR and 121 receiving LR. The duration of the median follow-up period was 45 months. The 1-year, 3-year, and 5-year OS rates were 95, 70, and 70% for patients in the neoRT+LR group, and 82, 64, and 54% for patients in the LR group, respectively. The 1-year, 3-year, 5-year DFS rates were 71, 53, and 37% for patients in the neoRT+LR group, and 52, 38, and 34% for patients in the LR group, respectively. A successful matching of 37 patients was achieved through propensity-score analysis. OS and DFS after matching analysis was statistically different between the two groups ( P=0.0099, P=0.034, respectively). neoRT was an independent prognostic factor for OS and DFS [hazard ratio (HR)=0.47, 95% CI: 0.24-0.93; HR=0.56, 95% CI: 0.34-0.92, respectively]. According to matching analysis, there were no statistically significant differences observed in terms of baseline characteristics, surgical safety, and complications between the groups. Conclusion: Liver resection and neoRT can be advantageous for patients with centrally located HCC.

Comparison of aggressiveness in central versus peripheral T1a clear-cell renal cell carcinoma.

PURPOSE: This study aimed to estimate the difference between peripheral and central small renal lesions in terms of their oncologic potential. METHODS: Cross-sectional retrospective analysis of patients with small renal masses (T1a) who underwent surgical treatment between January 2008 and July 2019 at the affiliated hospital. Only patients with ccRCC pathology were included. Cases were divided into 2 groups depending on tumor location (central or peripheral) based on the R.E.N.A.L and local nephrometry scoring. Presence of nodal involvement, distant metastases, ISUP grade and endophytic growth were defined as aggressiveness predictors. Statistical analyses was performed using a standard statistical software (IBM SPPS Statistics Ver. 22), with P < 0.05 considered statistically significant. Associations between tumor location and Fuhrman grade, exo-/endophytic growth, TNM classification, and type of operation were tested using the Pearson χ² test and 1-way ANOVA test. RESULTS: Patients with centrally located tumors had a higher incidence of clinical and pathological lymph node involvement (P = 0.02, χ2 = 5.1). Patients in both groups had an equal number of distant metastases at the time of diagnosis (P = 0.3, χ2 = 0.8). The operation time was significantly longer in patients with central lesions, which obviously showed higher tumor complexity in this group (P < 0.005). Pathological evaluation revealed differences between ISUP grades in both groups (P < 0.005, χ2 = 29.9). Central masses were characterized by higher aggressiveness, indicating a worse prognosis. Furthermore, the cases in the first group were more often endophytic (P = 0.03, χ2 = 0.9). Nevertheless, this did not affect the surgical strategy in most cases with a tendency toward partial nephrectomy. Eventually, organ-sparing treatment was preferable in both groups (P = 0.13, χ2 = 2.29). CONCLUSION: Centrally located kidney cancer has showed in present study a higher incidence of high ISUP grade, regional nodal involvement and endophytic growth type. Endophytic growth type was associated with worse ISUP grading. Distribution of ISUP grade was not age depended, thus showing no difference by this criterion, when comparing different age groups. Higher ISUP grade was strongly associated with presence of distant metastases in T1a kidney tumors. Further analysis is needed to investigate aggressiveness of centrally located T1a RCC, as it may influence current conservative management options.

Stereotactic body radiation therapy in patients with centrally located hepatocellular carcinoma: A retrospective, single-arm, multi-center study.

Centrally located hepatocellular carcinoma (HCC) is difficult to be radically resected due to its special location close to major hepatic vessels. Thus, we aimed to assess whether stereotactic body radiation therapy (SBRT) can be an effective and safe approach for centrally located HCC. This retrospective study included 172 patients with centrally located HCC who were treated with SBRT. Overall survival (OS) was analyzed as the primary endpoint. Rates of progression-free survival (PFS), local control, intrahepatic relapse, extrahepatic metastasis and toxicities were analyzed as secondary endpoints. The OS rates of 1-, 3-, and 5-year were 97.7%, 86.7%, and 76.3%, respectively. The PFS/local control rates of 1-, 3-, and 5-year were 94.1%/98.2%, 76.8%/94.9%, and 59.3%/92.3%, respectively. The cumulative incidence of intrahepatic relapse/extrahepatic metastases of 1-, 3-, and 5-year were 3.7%/2.9%, 25.0%/7.4%, and 33.3%/9.8%, respectively. Both univariate and multivariate analyses revealed that patients received BED10 at 100 Gy or more had better OS. Radiation-related adverse events were mild to moderate according to Common Terminology Criteria for Adverse Events, and no toxicities over grade 3 were observed. Patients with centrally located HCC in our cohort who received SBRT had similar OS and PFS rates compared to those reported in literatures who received surgery with neoadjuvant or adjuvant intensity-modulated radiation therapy. These results indicate that SBRT is an effective and well-tolerated method for patients with centrally located HCC, suggesting that it may serve as a reasonable alternative treatment for these kind of patients.

Minimally invasive surgery role in central squamous lung cancer after neoadjuvant chemoimmunotherapy.

Background: The present body of literature provides restricted evidence concerning the application of video-assisted thoracoscopic surgery (VATS) in individuals diagnosed with centrally located, locally advanced, and initially surgically challenging squamous cell lung carcinoma (SqCLC) following neoadjuvant chemoimmunotherapy (CIT). Further research is warranted to elucidate the role and potential benefits of VATS in this particular patient population. Methods: We performed a retrospective analysis on individuals diagnosed with centrally located and locally advanced SqCLC who received preoperative CIT at a single institution. The study evaluated the percentage of VATS performed, conversion rates, and perioperative outcomes. Furthermore, survival outcomes related to the resection extent were compared between patients who underwent standard lobectomy (SL) and extended lobectomy (EL, e.g., sleeve, bilobectomy or pneumonectomy) after neoadjuvant CIT. Results: A total of 27 cases of centrally located SqCLC underwent neoadjuvant CIT followed by VATS, with one case requiring conversion to thoracotomy due to adhesions. Comparison of perioperative outcomes and long-term cancer-specific mortality between the VATS group (N=24) and the thoracotomy group (N=13) did not yield any statistically significant differences. However, the VATS group exhibited a significantly higher frequency of SL (66.7% vs. 30.8%, P=0.046). Notably, within the VATS group, all three patients who experienced tumor relapse or died due to tumor recurrence were from the SL subgroup. Conclusions: This study contributes valuable real-world evidence demonstrating the feasibility and safety of utilizing VATS in the management of patients with centrally located and locally advanced SqCLC following neoadjuvant CIT. However, careful consideration might be given to the extent of resection to optimize patient long-term outcomes.

Volume increase and spatial shifts of chromosome territories in nuclei of radiation-induced polyploidizing tumour cells.

The exposure of tumour cells to high doses of ionizing radiation can induce endopolyploidization as an escape route from cell death. This strategy generally results in mitotic catastrophe during the first few days after irradiation. However, some cells escape mitotic catastrophe, polyploidize and attempt to undergo genome reduction and de-polyploidization in order to create new, viable para-diploid tumour cell sub-clones. In search for the consequences of ionizing radiation induced endopolyploidization, genome and chromosome architecture in nuclei of polyploid tumour cells, and sub-nuclei after division of bi- or multi-nucleated cells were investigated during 7 days following irradiation. Polyploidization was induced in p53-function deficient HeLa cells by exposure to 10Gy of X-irradiation. Chromosome territories #1, #4, #12 and centromeres of chromosomes #6, #10, #X were labelled by FISH and analysed for chromosome numbers, volumes and spatial distribution during 7 days post irradiation. The numbers of interphase chromosome territories or centromeres, respectively, the positions of the most peripherally and centrally located chromosome territories, and the territory volumes were compared to non-irradiated controls over this time course. Nuclei with three copies of several chromosomes (#1, #6, #10, #12, #X) were found in the irradiated as well as non-irradiated specimens. From day 2 to day 5 post irradiation, chromosome territories (#1, #4, #12) shifted towards the nuclear periphery and their volumes increased 16- to 25-fold. Consequently, chromosome territories returned towards the nuclear centre during day 6 and 7 post irradiation. In comparison to non-irradiated cells (∼500µm(3)), the nuclear volume of irradiated cells was increased 8-fold (to ∼4000µm(3)) at day 7 post irradiation. Additionally, smaller cell nuclei with an average volume of about ∼255µm(3) were detected on day 7. The data suggest a radiation-induced generation of large intra-nuclear chromosome territories and their repositioning prior to genome reduction.

Clinical Benefits of Neoadjuvant Radiotherapy on the Postoperative Recurrence of Centrally Located Hepatocellular Carcinoma: A Real-World Evidence Based on Phase II Clinical Trial.

Objective: Although surgical resection is one of the most effective way to treat liver cancer, its efficacy and safety in treatment of centrally located hepatocellular carcinoma (HCC) remains elusive. Therefore, it is very important to find a comprehensive treatment mode, such as radical resection combined with neoadjuvant radiotherapy (neoRT). Methods: The centrally located HCC patients who underwent radical resection from July 2015 to April 2021 were enrolled. According to whether the neoRT was implemented or not, these patients were allocated into neoadjuvant radiotherapy combined with liver resection (neoRT+LR) and liver resection alone (LR) group. The research method used propensity-score analysis and Cox proportional-hazards regression models. We generated an E-value to assess the sensitivity to unmeasured confounding. This study is a real-world, retrospective study based on phase II clinical trial. Results: A total of 168 patients were enrolled, including 38 patients treating with neoRT+LR and 130 patients with LR. The 1-, 3-, 5-year disease free survival (DFS) rates were 74%, 55% and 39% in the neoRT+LR group, and 44%, 28%, and 24% in the LR group, respectively. Neoadjuvant radiotherapy was an independent prognostic factor for postoperative recurrence ([HR]0.42, 95% CI [0.25, 0.69]). There was significant association between neoRT+LR and longer disease-free survival (Match, [HR] 0.43, 95% CI [0.24, 0.76]; GenMatch, [HR] 0.32, 95% CI [0.23, 0.43]; Adjusted for propensity score, [HR] 0.41, 95% CI [0.23, 0.73]; Inverse probability weighting, [HR] 0.38, 95% CI [0.22, 0.65], respectively). DFS before and after matching analysis was statistically different in two groups (p-value=0.005, p-value=0.0024, respectively). Neoadjuvant radiotherapy can significantly reduce the postoperative early recurrence (p-value <0.05). E-value analysis suggested robustness to unmeasured confounding. Conclusion: Liver resection combined with neoadjuvant radiotherapy was effective and safe for treatment of centrally located HCC patients, which improved the prognosis of patients and reduced the incidence of early recurrence.

Elevation of the Neutrophil-to-Lymphocyte Ratio Is a Significant Postoperative Poor Prognostic Factor in Patients With Clinical T3-4 Centrally Located Primary Lung Cancer.

BACKGROUND/AIM: In centrally located non-small cell lung cancer (CLNSCLC) surgery, large tumors and extension to neighboring structures prevent the attainment of adequate surgical fields and make operations more difficult, and some patients have extremely poor outcomes. This study aimed to identify novel postoperative prognostic factors in patients with advanced CLNSCLC. PATIENTS AND METHODS: CLNSCLC was defined as a tumor requiring pneumonectomy or sleeve lobectomy for complete removal. We retrospectively investigated the clinical courses of 35 patients with cT3-4 CLNSCLC. RESULTS: This study included 21 patients with cT3 and 14 with cT4 lung cancer. Nine patients underwent pneumonectomy and 26 underwent sleeve lobectomy. Univariate analysis revealed that a high neutrophil-to-lymphocyte ratio (NLR, p=0.005) and carcinoembryonic antigen (CEA) positivity (p=0.028) were significant poor prognostic factors. Only high NLR (p=0.020) was a significant independent predictor in multivariate analysis. Nine of 16 patients with high NLR (56%) experienced disease recurrence, whereas 6 of 19 patients without high NLR (32%) had recurrent disease. CONCLUSION: High NLR and CEA positivity were significant poor prognostic factors in patients with cT3-4 CLNSCLC, and only high NLR was an independent predictor. Our findings may be helpful in selecting optimal treatments for advanced CLNSCLC.

Long-term Outcomes After Moderate Hypofractionated Proton Therapy for Centrally Located Non-small Cell Lung Cancer.

BACKGROUND/AIM: To investigate the outcomes of patients with centrally located non-small-cell lung cancer (NSCLC) treated with proton beam therapy (PBT) using moderate hypofractionation. PATIENTS AND METHODS: Between 2006 and 2019, 34 patients with centrally located T1-T4N0M0 NSCLC who received moderate hypofractionated PBT were retrospectively reviewed. RESULTS: The median follow-up was 50.8 months (range=5.8-100.4 months). The 3-year overall survival, progression-free survival (PFS), and local control rates were 70.4%, 55.5% and 80.5%, respectively. Grade 2 or 3 lung adverse events (AEs) after PBT were observed in five (14.7%) patients; however, grade 3 radiation pneumonitis was observed in one (2.9%) patient. Notably, no grade 4 or higher AEs were observed. Regarding the correlation between the lung dose and proximal bronchial tree maximum dose and grade 2 or higher lung AEs, a weak correlation was observed between the mean lung dose and AEs (p=0.035). Although the clinical target volume (CTV) was a risk factor for poor PFS, no significant correlation was found between the CTV and lung AEs after PBT. CONCLUSION: Moderate hypofractionated PBT may be a useful radiotherapy method for centrally located cT1-T4N0M0 NSCLC.

In 18F-positron emission tomography/computed tomography-guided precision radiotherapy for centrally located non-small cell lung cancer, tumor related atelectasis is a prognostic factor of survival.

Purpose: Tumor related atelectasis(TRA) is an essential factor affecting survival that can cause chest pain, cough, hemoptysis, chest tightness, dyspnea, and even death. In the current study, we explored the possible impact of TRA on survival in cancer patients and the guiding significance of 18F-positron emission tomography/computed(PET/CT) in radiotherapy for patients with atelectasis tumors. Methods: In this retrospective study, we analyzed the treatment model and survival of patients with centrally located non-small cell lung cancer(NSCLC) treated with radiotherapy at two medical centers between May 2005 and August 2019. We identified 152 eligible patients and used propensity score matching (1:1) to process the data to reduce confounding factors, data bias, and mal-distribution. Results: We used propensity scores created well-matched groups of 57 patients overall with or without TRA. The one-year survival rate of all patients was 71.9%, and the two-year survival rate was 33.3%. Compared to the atelectasis group, the overall survival (OS) of patients in the non-atelectasis group was significantly prolonged (25 months vs. 17 months, p = 0.004), as well as in the atelectasis recovery group (28 months vs. 14 months, p = 0.008). In multivariate analysis, non-atelectasis was closely correlated with favorable OS (HR, 1.804 (-2.840); 95% CI, 1.145-2.840; p = 0.011). Conclusion: PET/CT can accurately stage NSCLC and better guide the treatment of NSCLC complicated with atelectasis. Tumor-associated atelectasis in patients with centrally located NSCLC can lead to is a poor prognostic marker.

Elevation of Neutrophil-to-Lymphocyte Ratio Is a Significant Poor Prognostic Factor in Completely Resected Centrally Located Lung Squamous Cell Carcinoma.

BACKGROUND/AIM: The neutrophil-to-lymphocyte ratio (NLR) plays key roles in cancer growth. This study aimed to identify novel prognostic factors in patients who underwent complete resection of centrally located lung squamous cell carcinoma. PATIENTS AND METHODS: We retrospectively investigated the clinical courses of 45 patients who underwent sleeve lobectomy or pneumonectomy for centrally located squamous cell carcinoma. RESULTS: High NLR (p<0.001) and pathological T3/4 (p=0.008) were significant poor prognostic factors according to univariate analysis. Patients with pathological N2 had poor prognosis; however, there was no significant difference (p=0.095). Among these factors, only high NLR (p=0.003) was an independent poor prognostic factor according to multivariate analysis. Of the 23 patients with high NLR, 11 (49%) had recurrence, whereas in the 22 patients without high NLR, only two (9%) had recurrence. CONCLUSION: High NLR is an independent poor prognostic factor in centrally located lung squamous cell carcinoma. Our findings may guide the selection of optimal treatments for this subgroup of patients.

Impact of Central Airway Infiltration Type in Primary Lung Cancer Patients Treated With Sleeve Lobectomy.

BACKGROUND/AIM: There are two types of lung cancer cell infiltration into the central airway. One is when a centrally located lung cancer directly infiltrates the central airway and the other is when cancer cells in the metastatic hilar lymph node infiltrate the central airway. We aimed to identify the impact of central airway infiltration type on the clinical features of patients undergoing sleeve lobectomy. PATIENTS AND METHODS: The clinical courses of 58 primary lung cancer patients who underwent sleeve lobectomy between January 2010 and December 2020 were investigated. RESULTS: Primary tumors directly infiltrated into the central airway in 42 patients, whereas 16 patients had infiltration of cancer cells from the metastatic hilar lymph node. Primary tumor infiltration was a poor prognostic factor according to both univariate (p=0.016) and multivariate analyses (p=0.042). Operation times (p=0.240) and incidences of adverse events (p=0.926) were not associated with the type of central airway infiltration. CONCLUSION: The type of airway infiltration was an independent poor prognostic factor after sleeve lobectomy in primary lung cancer patients. Our findings may guide the selection of optimal treatments for this patient population.

Different occurrence rates of centrally located cytoplasmic granulation in one cohort oocytes show distinctive embryo competence and clinical outcomes.

Centrally located cytoplasmic granulation (central granulation) is a common cytoplasmic dysmorphism in human oocytes retrieved after controlled ovarian hyperstimulation (COH). In order to achieve a better understanding of its formation and effects on clinical outcomes, we retrospectively analyzed 422 ICSI treatment cycles. Three groups of patients were classified according to the ratio of central granulation occurrence in one egg cohort, as partial granulation, all granulation and control groups. The partial granulation group had a significantly lower BMI and higher AMH level compared to the control or all granulation groups. Consistent with these distinctive features in the partial granulation group, fertilization and blastocyst formation rates were reduced significantly in the partial granulation group but not in the all granulation group. Furthermore, the clinical outcomes in fresh embryo transfer cycles were dramatically reduced in the partial granulation group compared with the control group. However, in FET cycles, all three clinical outcomes were significantly reduced in the all granulation group but not in the partial granulation group. We propose that partial granulation may reflect a specific population of patients, and that the central granulation structure is sensitive to cryopreservation.