Differentiation of high-grade and low-grade diffuse gliomas by intravoxel incoherent motion MR imaging

Background

Our aim was to assess the diagnostic performance of intravoxel incoherent motion (IVIM) MR imaging for differentiating high-grade gliomas (HGGs) from low-grade gliomas (LGGs).

Methods

Forty-five patients with diffuse glioma (age 50.9 ± 20.4 y; 26 males, 19 females) were assessed with IVIM imaging using 13 b-values (0–1000 s/mm²) at 3T. The perfusion fraction (f), true diffusion coefficient (D), and pseudo-diffusion coefficient (D*) were calculated by fitting the bi-exponential model. The apparent diffusion coefficient (ADC) was obtained with 2 b-values (0 and 1000 s/mm²). Relative cerebral blood volume was measured by the dynamic susceptibility contrast method. Two observers independently measured D, ADC, D*, and f, and these measurements were compared between the LGG group (n = 16) and the HGG group (n = 29).

Results

Both D (1.26 ± 0.37 mm²/s in LGG, 0.94 ± 0.19 mm²/s in HGG; P < .001) and ADC (1.28 ± 0.35 mm²/s in LGG, 1.03 ± 0.19 mm²/s in HGG; P < .01) were lower in the HGG group. D was lower than ADC in the LGG (P < .05) and HGG groups (P < .0001). D* was not different between the groups. The f-values were significantly larger in HGG (17.5 ± 6.3%) than in LGG (5.8 ± 3.8%; P < .0001) and correlated with relative cerebral blood volume (r = 0.85; P < .0001). Receiver operating characteristic analyses showed areas under curve of 0.95 with f, 0.78 with D, 0.73 with ADC, and 0.60 with D*.

Conclusion

IVIM imaging is useful in differentiating HGGs from LGGs.     

Radiographic Progression and Survival of the Different HRCT Patterns of Idiopathic Pulmonary Fibrosis

Introduction.Idiopathic pulmonary fibrosis (IPF) is a chronic disease with a peculiar (typical) HRCT pattern, but biopsy can demonstrate usual interstitial pneumonia in patients with atypical patterns. It is unknown how progression pattern varies among different radiographic presentations of IPF. We sought to investigate the longitudinal radiographic evolution and survival of typical and non-typical patterns.Materials and Methods.One-hundred-twenty-three patients diagnosed with IPF in 2 tertiary referral hospitals were included in the study. Longitudinal evolution of non-typical patterns was considered. The HRCT visual fibrosis score was used as a reliable evaluation tool of disease progression. HRCTs were scored by 2 senior chest radiologists with ILD expertise. The primary endpoint was the evolution of the presentation pattern to probable or typical. The secondary endpoint was lung transplant (LTx)-free survival from the time of diagnosis.Results.Average interval between HRCTs was 16±5 months; average follow-up after the 2^nd HRCT was 17±11 months. Four out of 45 (8.9%) patients with probable pattern “evolved” to a typical pattern of IPF, while 5 out of 31 (16.1%) with indeterminate/alternative pattern “evolved” to probable pattern. An average HRCT fibrosis score increase of 9±11% was observed with typical (n=49), 6±5% with probable (n=43) and 7±8% (n=31) with indeterminate/alternative presentation pattern. LTx-free survival and lung function declines did not show any difference related to presentation HRCT patterns.Conclusions.The evolution of a non-typical UIP pattern to a typical one is infrequent. All presentation HRCT patterns of IPF evolve in similar way and are associated with comparable survival time.[/sc]     

Efficacy and safety of larotrectinib in TRK fusion-positive primary central nervous system tumors

BackgroundLarotrectinib is a first-in-class, highly selective tropomyosin receptor kinase (TRK) inhibitor approved to treat adult and pediatric patients with TRK fusion-positive cancer. The aim of this study was to evaluate the efficacy and safety of larotrectinib in patients with TRK fusion-positive primary central nervous system (CNS) tumors.MethodsPatients with TRK fusion-positive primary CNS tumors from two clinical trials ({"type":"clinical-trial","attrs":{"text":"NCT02637687","term_id":"NCT02637687"}}NCT02637687, {"type":"clinical-trial","attrs":{"text":"NCT02576431","term_id":"NCT02576431"}}NCT02576431) were identified. The primary endpoint was investigator-assessed objective response rate (ORR).ResultsAs of July 2020, 33 patients with TRK fusion-positive CNS tumors were identified (median age: 8.9 years; range: 1.3–79.0). The most common histologies were high-grade glioma (HGG; n = 19) and low-grade glioma (LGG; n = 8). ORR was 30% (95% confidence interval [CI]: 16–49) for all patients. The 24-week disease control rate was 73% (95% CI: 54–87). Twenty-three of 28 patients (82%) with measurable disease had tumor shrinkage. The 12-month rates for duration of response, progression-free survival, and overall survival were 75% (95% CI: 45–100), 56% (95% CI: 38–74), and 85% (95% CI: 71–99), respectively. Median time to response was 1.9 months (range 1.0–3.8 months). Duration of treatment ranged from 1.2–31.3+ months. Treatment-related adverse events were reported for 20 patients, with grade 3–4 in 3 patients. No new safety signals were identified.ConclusionsIn patients with TRK fusion-positive CNS tumors, larotrectinib demonstrated rapid and durable responses, high disease control rate, and a favorable safety profile.     

Cerebellar location may predict an unfavourable prognosis in paediatric high-grade glioma

Background:

High-grade glioma (HGG) of the cerebellum accounts for only 5% of paediatric HGG. Since little is known about these tumours, the present study aimed at their further characterisation.

Methods:

Twenty-nine paediatric patients with centrally reviewed cerebellar HGG were identified from the HIT-GBM/HIT-HGG database. Clinical and epidemiological data were compared with those of 180 paediatric patients with cortical HGG.

Results:

Patients with cerebellar tumours were younger (median age of 7.6 vs 11.7 years, P=0.028), but both groups did not differ significantly with regard to gender, tumour predisposing syndromes, secondary HGG, primary metastasis, tumour grading, extent of tumour resection, chemotherapy regimen, or radiotherapy. Except for an increased incidence of anaplastic pilocytic astrocytoma (APA) in the cerebellar subset (20.7% vs 3.3% P<0.001), histological entities were similarly distributed in both groups. As expected, tumour grading had a prognostic relevance on survival. Compared with cortical HGG, overall survival in the cerebellar location was significantly worse (median overall survival: 0.92±0.02 vs 2.03±0.32 years; P=0.0064), and tumour location in the cerebellum had an independent poor prognostic significance as shown by Cox-regression analysis (P=0.019).

Conclusion:

High-grade glioma represents a group of tumours with an obviously site-specific heterogeneity associated with a worse survival in cerebellar location.     

Excellent outcome of young children with nodular desmoplastic medulloblastoma treated on “Head Start” III: a multi-institutional,prospective clinical trial

Background“Head Start” III, was a prospective clinical trial using intensive induction followed by myeloablative chemotherapy and autologous hematopoietic cell rescue (AuHCR) to either avoid or reduce the dose/volume of irradiation in young children with medulloblastoma.MethodsFollowing surgery, patients received 5 cycles of induction followed by myeloablative chemotherapy using carboplatin, thiotepa, and etoposide with AuHCR. Irradiation was reserved for children >6 years old at diagnosis or with residual tumor post-induction.ResultsBetween 2003 and 2009, 92 children <10 years old with medulloblastoma were enrolled. Five-year event-free survival (EFS) and overall survival (OS) rates (±SE) were 46 ± 5% and 62 ± 5% for all patients, 61 ± 8% and 77 ± 7% for localized medulloblastoma, and 35 ± 7% and 52 ± 7% for disseminated patients. Nodular/desmoplastic (ND) medulloblastoma patients had 5-year EFS and OS (±SE) rates of 89 ± 6% and 89 ± 6% compared with 26 ± 6% and 53 ± 7% for classic and 38 ± 13% and 46 ± 14% for large-cell/anaplastic (LCA) medulloblastoma, respectively. In multivariate Cox regression analysis, histology was the only significant independent predictor of EFS after adjusting for stage, extent of resection, regimen, age, and sex (P <0.0001). Five-year irradiation-free EFS was 78 ± 8% for ND and 21 ± 5% for classic/LCA medulloblastoma patients. Myelosuppression was the most common toxicity, with 2 toxic deaths. Twenty-four survivors completed neurocognitive evaluation at a mean of 4.9 years post-diagnosis. IQ and memory scores were within average range overall, whereas processing speed and adaptive functioning were low-average.ConclusionWe report excellent survival and preservation of mean IQ and memory for young children with ND medulloblastoma using high-dose chemotherapy, with most patients surviving without irradiation.     

Treatment of embryonal tumors with multilayered rosettes with carboplatin/etoposide induction and high-dose chemotherapy within the prospective P-HIT trial

BackgroundEmbryonal tumors with multilayered rosettes (ETMR) are highly aggressive tumors occurring in early childhood. Published clinical data refer to retrospective, heterogeneously treated cohorts. Here, we describe the outcome of patients treated according to the prospective P-HIT trial and subsequent HIT2000-interim-registry.Patients and methodsAge-stratified treatment included carboplatin/etoposide induction, tandem high-dose chemotherapy (“CARBO/ETO + HDCT”), and response-stratified radiotherapy. Patients with centrally reviewed neuropathological and molecularly confirmed diagnosis of ETMR recruited within the P-HIT trial (2001-2011; n = 19), the HIT2000-interim-registry (2012-2014; n = 12), and earlier HIT trials (n = 4) were selected for analysis.ResultsAge-adjusted incidence rate was 1.35 per 1 million children (aged 1-4 years) in the years 2012-2014. Median age at diagnosis for 35 patients was 2.9 years. Metastases at diagnosis were detected in 9 patients. One patient died due to postoperative complications. For 30 patients with non-brainstem tumor location, 5-year progression-free survival (PFS) and overall survival (OS) were 35% and 47% after treatment with CARBO/ETO + HDCT (n = 17), compared to 0% and 8% with other treatments (n = 13, P[OS] = .011). All 4 patients with brainstem tumor died within 10 months after diagnosis. By multivariable analysis, supratentorial location: (HR [PFS]: 0.07 [95%CI: 0.01-0.38], P = .003), localized disease (M0): (HR [OS] M0, no residual tumor: 0.30 [95%CI: 0.009-1.09], P = .068; M0, residual tumor: 0.18 [95%CI: 0.04-0.76], P = .020), and CARBO/ETO + HDCT treatment (HR [OS]: 0.16 [95%CI: 0.05-054], P = .003) were identified as independent prognostic factors. Of 9 survivors, 6 were treated with radiotherapy (craniospinal 4; local 2).ConclusionsOur data indicate improved survival with intensified chemotherapy (CARBO/ETO + HDCT). However, despite intensive treatment, the outcome was poor. Thus, innovative therapies need to be evaluated urgently in an upfront setting.     

MLH1 promoter hypermethylation predicts poorer prognosis in mismatch repair deficiency endometrial carcinomas

ObjectiveThe antitumor effects of anti-PD-1 antibody against mismatch repair deficiency (MMR-D)-associated cancers have been reported. MMR-D is found in approximately 20%–30% of endometrial carcinomas (ECs) and frequently occurs due to MLH1 promoter hypermethylation (MLH1-PHM). ECs with MLH1-PHM are classified according to the molecular screening of Lynch syndrome (LS), but few detailed reports are available. The purpose of this study was to clarify the clinical features of EC with MLH1-PHM.MethodsImmunohistochemistry of MMR proteins (MLH1, MSH2, MSH6, and PMS2) was performed on specimens from 527 ECs treated at our university hospital from 2003 to 2018. MLH1 methylation analysis was added to cases with MLH1/PMS2 loss. ECs were classified as follows: cases that retained MMR proteins as “MMR-proficient;” cases with MLH1/PMS2 loss and MLH1-PHM as “met-EC;” and cases with other MMR protein loss and MLH1/PMS2 loss without MLH1-PHM as “suspected-LS.” The clinical features, including long-term prognosis, of each group, were analyzed.ResultsAccordingly, 419 (79.5%), 65 (12.3%), and 43 (8.2%) cases were categorized as “MMR-proficient,” “suspected-LS,” and “met-EC,” respectively. Significantly, “met-EC” had a lower proportion of grade 1 tumors (37.5%) and a higher proportion of stage III/IV tumors (37.2%) than the other groups. The overall and progression-free survival of “met-EC” were significantly worse than those of “suspected-LS” in all cases.ConclusionIn ECs with MMR-D, “met-ECs” were a subgroup with a poorer prognosis than “suspected-LS.” “Met-ECs” would be the main target for anti-PD-1 antibody treatment, and its clinical susceptibility should be verified individually.     

Does 1-minute walk test predict results of 6-minute walk test in patients with idiopathic pulmonary fibrosis?

Background:The six-minute walk test (6MWT) is a readily available tool used to evaluate functional capacity in patients with idiopathic pulmonary fibrosis (IPF). However, it is often logistically challenging to perform in the context of a busy clinical practice. We sought to investigate if the 1MWT distance (1MWD) predicts the 6MWT distance (6MWD), and if an abbreviated walk could accurately predict outcomes in IPF patients.Methods:Baseline demographics and pulmonary function testing of IPF patients evaluated at a tertiary referral center between 2010 and 2017 were collected. 6MWT variables at baseline as well as 1 and 6 minutes were collected. Time to death, lung transplantation, or most recent follow-up was ascertained.Results:There were 177 patients, the majority of whom (80%) were male. The mean age was 67 ± 9 years and mean FVC was 64 ± 18% predicted. Forty eight (27%) patients used oxygen supplementation during the 6MWT. The median 6MWD was 366 meters (IQR: 268-471) while the median 1MWD was 65 meters (IQR: 46-81). Stratified by the median, 89 patients were “High Walkers” based on the 6MWD ≥ 366m (HW₆) and 88 patients were “Low Walkers” (LW₆). HW₆ had a higher FVC% (70 ± 15 vs 57 ± 18, p= 0.001), higher DLCO% (45 ± 12 vs 34 ± 14, p= 0.001) and higher 1MWD (83 ± 28 vs 47 ± 16, m p= 0.001). Median transplant-free survival was better in HW₆ vs LW₆ (27 ± 16 vs 22 ± 18 months, log rank p= 0.018). There was a strong correlation between the 1MWD and the 6MWD (r= 0.91, Spearman’s correlation, p < 0.0001). Also, the transplant-free survival curves stratified by 1MWD were very similar to the curves for 6MWD, showing a lower survival in the LW₁ cohort (log rank p= 0.009).Conclusion:The 1MWD obtained during the first minute of a 6MWD shows a strong correlation to total 6MWD and retains its ability to predict transplant-free survival. 1MWT may serve as a practical substitute for the more cumbersome 6MWT. Our findings require further validation prospectively in larger cohorts of IPF patients.     

Comparative study on short-term efficacy of single incision plus one (SI+1) port and multiportal 3D laparoscopic minimally invasive esophagectomy

BackgroundTo evaluate the safety and efficacy of single incision plus one (SI+1) port three-dimensional (3D) laparoscopic minimally invasive esophagectomy (MIE).MethodsClinical data of patients who underwent 3D thoracic laparoscopic MIE in our department from September 2020 to March 2021 were analyzed retrospectively. According to the different methods of laparoscopic surgery, the patients were divided into 2 groups: SI+1 port 3D laparoscopy group and multiportal 3D laparoscopy group. The operation time of the 3D laparoscopy component, amount of intraoperative blood loss, number of celiac lymph node dissections, postoperative abdominal drainage days, postoperative total abdominal drainage, postoperative complications, and length of hospital stay were analyzed.ResultsThere was no significant difference between the 2 methods in laparoscopic operation time (30.11±5.86 vs. 28.45±4.72 min, P=0.49), intraoperative blood loss (34.44±9.82 vs. 35.91±6.25 mL, P=0.69), number of celiac lymph node dissections (8.44±3.13 vs. 7.09±2.12, P=0.27), postoperative abdominal drainage days (3.11±0.33 vs. 3.00±0.00 days, P=0.28), postoperative total abdominal drainage (95.00±23.33 vs. 92.27±11.26 mL, P=0.74), postoperative complications (22.2% vs. 27.3%, P=0.33), and hospital stay (9.67±0.71 vs. 10.18±0.87 days, P=0.17). None of the patients enrolled in the study had recurrence or death to date.ConclusionsThe application of SI+1 port 3D laparoscopy in minimally invasive resection of esophageal carcinoma is safe and feasible.     

Histological Findings of Mammary Gland Development and Risk of Breast Cancer in BRCA1 Mutant Mouse Models

PurposeThe breast cancer susceptibility gene, BRCA1, is involved in normal development and carcinogenesis of mammary glands. Here, we aimed to evaluate the relationship between histological findings of mammary gland development and breast cancer risk in BRCA1 mutant mice.MethodsFive BRCA1 mutant mice and five non-mutant FVB/NJ mice were used for each group of 1-month-old (pubertal), 3-month-old (fertile), and 8-month-old (menopausal) mice. In another experiment, 15 BRCA1 mutant mice were followed up to 8 months after birth and classified into tumor-bearing (11 mice) and tumor-free (4 mice) groups. Excised mammary gland tissues were stained with Carmine Alum, and the number of terminal end buds (or alveolar buds), branching density, and duct elongation were measured using image analysis programs. Differences between the two groups were assessed using paired t-test.ResultsOne-month-old BRCA1 mutant mice showed a higher number of terminal end buds (23.8 ± 1.0 vs. 15.6 ± 0.8, p = 0.0002), branching density (11.7 ± 0.4 vs. 9.6 ± 0.5%, p = 0.0082), and duct elongation (9.7 ± 0.7 vs. 7.3 ± 0.4 mm, p = 0.0186) than controls. However, there was no difference between the 3- and 8-month-old groups. In BRCA1 mutant mice, the tumor-bearing group showed a significantly higher number of alveolar buds (142.7 ± 5.5 vs. 105.5 ± 5.4, p = 0.0008) and branching density (30.0 ± 1.0 vs. 24.1 ± 1.1%, p = 0.008) than the tumor-free group; however, duct elongation was not different (23.9 ± 0.6 vs. 23.6 ± 0.6 mm, p = 0.8099) between the groups.ConclusionBRCA1 mutant mice exhibited early pubertal mammary gland development and delayed age-related mammary gland involution was associated with breast cancer. Our results may have clinical implications for predicting breast cancer risk and developing prevention strategies for BRCA1 mutation carriers.     

Prospective evaluation of local control and late effects of conformal radiation therapy in children,adolescents, and young adults with high-grade glioma

Background

A phase II trial of conformal radiotherapy (CRT) for pediatric high-grade glioma (HGG) was performed to evaluate disease control and late effects.

Methods

Between July 1997 and January 2003, 34 pediatric patients (median age, 13.2 ± 6.7 years) with HGG were enrolled on an International Commission on Radiation Units and Measurements Report 50-compliant prospective trial using CRT with a 2 cm clinical target volume margin. Baseline and serial evaluations were performed to assess functional outcomes.

Results

Median follow-up for the entire group was 18 months (range, 2–134 months). Twenty (58.8%) patients developed local progression, and 6 (17.6%) patients developed distant progression. Progression-free and overall survival at 10 years were 18.8% ± 6.9% and 16.8% ± 6.5%, respectively. At baseline, 40% of patients evaluated for intelligence quotient (IQ) scored below 85. Measures of cognitive function obtained during the first 12 months fit a mixed model with a quadratic function. The relationship between IQ and time was -1.1883 points/month for the linear term and 0.07728 points/month for the quadratic term (P = .0454). IQ decreased between baseline and 6 months and then increased slightly through 12 months. The opposite was found for (all P values of the quadratic term) activities of daily living (P = .0155), socialization (P = .0049), and the composite score (P = .0257) of adaptive behavior.

Conclusion

CRT using a 2 cm clinical target volume margin in pediatric HGG demonstrated tumor control comparable to conventional radiation therapy. Disrupted cognitive and adaptive behavioral functioning were present at baseline and throughout the course of disease.     

Analysis of safety and efficacy of laparoscopic radical gastrectomy combined with or without indocyanine green tracer fluorescence technique in treatment of gastric cancer: a retrospective cohort study

BackgroundAn adequate resection margin and lymph node dissection are important factors for successful radical gastrectomy. The presence of near-infrared camera imaging with indocyanine green (ICG) gives new insight into radical gastrectomy. Laparoscopic radical gastrectomy with ICG is still in its initial stages and requires more evidence-based medical research. The aim of the present study was to evaluate the safety and availability of lymph node dissection and precise gastrectomy for gastric cancer patients undergoing radical resection under laparoscope with ICG, in the hope of providing evidence of application of ICG tracer fluorescence technique in radical gastrectomy.MethodsA retrospective cohort study was performed with 56 patients who underwent laparoscopic radical gastrectomy. The patients were categorized into the ICG (n=18) or the non-ICG (n=38) group based on whether preoperative endoscopic mucosal ICG injection was performed. Their clinical characteristics (age, tumor size, location, TNM stage and so on) were compared as baseline data. Perioperative outcomes (blood loss, time of first intestinal exhaust, early or long-term complications and so on) were used to assess safety. The status of lymph node dissection and tumor localization were analyzed to testify efficacy. SPSS version 26.0 was used for the statistical analysis.ResultsThere was no difference in clinical data at baseline. From the safety point of view, there was no difference in perioperative outcomes (operative time, blood loss, time of first intestinal exhaust and so on) between the two groups (all P>0.05). From the efficacy point of view, the number of lymph nodes <5 mm (21.84±1.86 vs. 16.24±2.10, P<0.001), the total number of lymph nodes (34.61±5.87 vs. 29.92±5.27, P=0.004), the number of lymph nodes dissected in perigastric regions (groups 1–7, 22.89±3.64 vs. 20.29±3.00, P=0.007), and the number of lymph nodes in extraperigastric regions (groups 8–12, 11.72±3.06 vs. 9.61±3.18, P=0.022) were greater in ICG group compared with non-ICG group. In ICG group, the average vertical distances between the top and bottom of the fluorescent edge and neoplastic edge were 2.65±0.58 and 2.67±0.65 cm, respectively. Fluorescent edge pathology was negative.ConclusionsICG fluorescence could be conducive to lymph node dissection and precise gastrectomy in laparoscopic radical gastrectomy.     

Hyperthermic intraperitoneal chemotherapy for gastric cancer with peritoneal metastasis: A multicenter propensity score-matched cohort study

ObjectiveSystemic chemotherapy has limited efficacy in the treatment of peritoneal metastasis (PM) in gastric cancer (GC). Hyperthermic intraperitoneal chemotherapy (HIPEC) combined with complete cytoreductive surgery (CRS) has shown promising outcomes but remains controversial. The present study aimed to evaluate the safety and efficacy of HIPEC without CRS in GC patients with PM.MethodsThis retrospective propensity score-matched multicenter cohort study included GC patients with PM treated with either chemotherapy alone (Cx group) or with HIPEC combined with chemotherapy (HIPEC-Cx group) in four Chinese high-volume gastric medical centers between 2010 and 2017. The primary outcomes were median survival time (MST) and 3-year overall survival (OS). Propensity score matching was performed to compensate for controlling potential confounding effects and selection bias.ResultsOf 663 eligible patients, 498 were matched. The MST in the Cx and HIPEC-Cx groups was 10.8 and 15.9 months, respectively [hazard ratio (HR)=0.71, 95% confidence interval (95% CI), 0.58−0.88; P=0.002]. The 3-year OS rate was 10.1% (95% CI, 5.4%−14.8%) and 18.4% (95% CI, 12.3%−24.5%) in the Cx and HIPEC-Cx groups, respectively (P=0.017). The complication rates were comparable. The time to first flatus and length of hospital stay for patients undergoing HIPEC combined with chemotherapy was longer than that of chemotherapy alone (4.6±2.4 dvs. 2.7±1.8 d, P<0.001; 14.2±5.8 dvs. 11.4±7.7 d, P<0.001), respectively. The median follow-up period was 33.2 months. ConclusionsCompared with standard systemic chemotherapy, HIPEC combined with chemotherapy revealed a statistically significant survival benefit for GC patients with PM, without compromising patient safety.     

Digestive tract reconstruction of laparoscopic total gastrectomy for gastric cancer: a comparison of the intracorporeal overlap,intracorporeal hand-sewn anastomosis,and extracorporeal anastomosis

BackgroundThe application of esophagojejunostomy has certain difficulties in totally laparoscopic total gastrectomy (TLTG). This is due to the higher requirement for surgical techniques and the lack of any unified standards. This study aim to explore the practicability and safety of intracorporeal overlap and intracorporeal hand-sewn anastomosis compared with extracorporeal anastomosis.MethodsThe clinical pathological data of 56 patients who underwent TLTG from March 2016 to December 2020 in the Harbin Medical University Cancer Hospital were retrospectively analyzed. According to the method of anastomosis, the patients were divided into the overlap (n=36) and the hand-sewn anastomosis (n=20). Patients who receive laparoscopic-assisted total gastrectomy (LATG; n=74) formed the control group. The basic clinical data, and intraoperative and postoperative results of the patients were assessed.ResultsCompared with the control group, the overlap anastomosis and hand-sewn anastomosis groups showed no significant differences in clinicopathological data and short-term postoperative recovery. There were no significant differences between the overlap and the control group in operation time nor anastomosis time. However, the anastomosis time of the hand-sewn anastomosis group was significantly prolonged compared to the control group (53.20±14.14 vs. 43.01±12.53 minutes, P=0.002). Compared with the control group, the operation cost was significantly higher in the overlap group (CNY 81,300±6,100 vs. CNY 76,600±6,800, P=0.001), but significantly lower in the hand-sewn anastomosis group (CNY 71,900±1,700 vs. CNY 76,600±6,800, P=0.003). Early postoperative complications occurred in 5 cases (13.9%) in the overlap group, 3 cases (15.0%) in the hand-sewn anastomosis group, and 11 cases (14.9%) in the control group. There were 3 cases (8.3%) of postoperative anastomotic-related complications in the overlap group. No anastomotic-related complications were observed in the hand-sewn anastomosis group.ConclusionsThe overlap anastomosis and hand-sewn anastomosis are practical and safe. Furthermore, the overlap anastomosis may be more suitable for patients with lower cardia and fundic lesions. The hand-sewn method has a wider range of indications pending advanced surgical skills, and is an effective supplementary technique for instrument anastomosis.     

Central Nervous System Efficacy of Furmonertinib (AST2818) Versus Gefitinib as First-Line Treatment for EGFR-Mutated NSCLC: Results From the FURLONG Study

IntroductionFurmonertinib (AST2818) is a pan-EGFR tyrosine kinase inhibitor with central nervous system (CNS) antitumor activity. We report the CNS efficacy of furmonertinib compared with gefitinib in untreated EGFR-sensitizing mutation-positive NSCLC from the FURLONG study.MethodsFURLONG was a randomized, double-blind, phase 3 study conducted in 55 hospitals in the People’s Republic of China. Patients 1:1 randomly received furmonertinib 80 mg once daily or gefitinib 250 mg once daily treatment. At screening, all the patients underwent brain imaging examination. Patients with asymptomatic steady CNS metastases at baseline constituted this preplanned CNS subgroup analysis.ResultsA total of 358 patients were enrolled in the FURLONG study. In the 133 (37%) patients who had measurable or nonmeasurable CNS lesions, CNS progression-free survival was 20.8 months (95% confidence interval [CI]: 15.2–25.3) in the furmonertinib group and 9.8 months (95% CI: 7.2–18.0) in the gefitinib group (hazard ratio = 0.40 [95% CI: 0.23–0.71], p = 0.0011). In the 60 patients (17%) who had measurable CNS lesions, CNS objective response rate was 91% (95% CI: 72–99) with furmonertinib and 65% (95% CI: 48–80) with gefitinib (OR = 6.82 [95% CI: 1.23–37.67], p = 0.0277). The least-square mean of CNS depth of response was 62% (95% CI: 51–72) in the furmonertinib group and 39% (95% CI: 30–47) in the gefitinib group, the mean difference was 23% (95% CI: 10–37, p = 0.0011).ConclusionsFurmonertinib first-line treatment was found to have superior efficacy in CNS progression-free survival, CNS objective response rate, and CNS depth of response compared with gefitinib in patients with EGFR-mutated NSCLC with CNS metastases.     

A modified MethyLight assay predicts the clinical outcomes of anti‐epidermal growth factor receptor treatment in metastatic colorectal cancer

DNA methylation status correlates with clinical outcomes of anti‐epidermal growth factor receptor (EGFR) treatment. There is a strong need to develop a simple assay for measuring DNA methylation status for the clinical application of drug selection based on it. In this study, we collected data from 186 patients with metastatic colorectal cancer (mCRC) who had previously received anti‐EGFR treatment. We modified MethyLite to develop a novel assay to classify patients as having highly methylated colorectal cancer (HMCC) or low‐methylated colorectal cancer (LMCC) based on the methylation status of 16 CpG sites of tumor‐derived genomic DNA in the development cohort (n = 30). Clinical outcomes were then compared between the HMCC and LMCC groups in the validation cohort (n = 156). The results showed that HMCC had a significantly worse response rate (4.2% vs 33.3%; P = .004), progression‐free survival (median: 2.5 vs 6.6 mo, P < .001, hazard ratio [HR] = 0.22), and overall survival (median: 5.6 vs 15.5 mo, P < .001, HR = 0.23) than did LMCC in patients with RAS wild‐type mCRC who were refractory or intolerable to oxaliplatin‐ and irinotecan‐based chemotherapy (n = 101). The DNA methylation status was an independent predictive factor and a more accurate biomarker than was the primary site of anti‐EGFR treatment. In conclusion, our novel DNA methylation measurement assay based on MethyLight was simple and useful, suggesting its implementation as a complementary diagnostic tool in a clinical setting.     

KMT2C promoter methylation in plasma‐circulating tumor DNA is a prognostic biomarker in non‐small cell lung cancer

MLL3 histone methyltransferase, encoded by the KMT2C gene, is a tumor suppressor that has an essential role in cell‐type‐specific gene expression. We evaluated the prognostic significance of KMT2C promoter methylation as a circulating epigenetic biomarker in plasma cell‐free DNA (cfDNA) in non‐small cell lung cancer (NSCLC). We examined the methylation status of KMT2C promoter using a novel highly specific and sensitive real‐time methylation‐specific PCR (MSP) assay in (a) operable NSCLC: 48 fresh‐frozen NSCLC tissues, their corresponding adjacent non‐neoplastic tissues, and 48 matched plasma samples; (b) metastatic NSCLC: 91 plasma samples; and (c) 60 plasma samples from healthy donors (HD). KMT2C promoter methylation in plasma cfDNA was detected in 7/48 (14.6%) patients with operable and in 18/91 (19.8%) patients with advanced NSCLC but in none (0/60, 0%) of the plasma samples from HD. In operable NSCLC, in corresponding adjacent non‐neoplastic tissue samples, KMT2C promoter methylation was detected in 3/48 (6.3%) cases. Moreover, in operable NSCLC, KMT2C promoter methylation in plasma cfDNA was related to reduced disease‐free survival (ΗR = 0.239; P = 0.001) and worse overall survival (OS; HR = 0.342, P = 0.023). In metastatic NSCLC, KMT2C promoter methylation in plasma cfDNA was related to worse progression‐free survival (PFS; HR = 0.431; P = 0.005) and worse OS (HR = 0.306; P < 0.001). Our data strongly suggest that the detection of KMT2C promoter methylation in plasma cfDNA predicts poor prognosis in patients with both operable and metastatic NSCLCs. KMT2C promoter methylation in plasma cfDNA therefore merits further evaluation and validation as a noninvasive circulating epigenetic biomarker.

Abbreviations

cfDNA

cell‐free DNA

CTCs

circulating tumor cells

gDNA

genomic DNA

HD

healthy donors

MSP

methylation‐specific PCR

NSCLC

non‐small cell lung cancer

SB

sodium bisulfite