Observation Research Articles

Influence of Polysaccharide from Helianthus tuberosus L. on Antiproliferative Activity of N-Glycoside Indolo[2,3-a]carbazole Derivative LCS-1269

The Lewis model of epidermoid carcinoma that developed in the lungs of F1(C57Bl/6 × DBA/2) hybrid mice has been used while investigating antitumor activity of the N-glycoside derivative indolo[2,3-a]carbazole (LCS-1269) with a polysaccharide from Helianthus tuberosus L. as an adjuvant agent. The antitumor effect of LCS-1269 together with the polysaccharide was evaluated by the inhibition of tumor growth in treated ani mals in comparison to the control group. As a result, it was found that combination of LCS-1269 with the polysaccharide from Helianthus tuberosus L. provided more pronounced therapeutic and longer-lasting effect than monotherapy showing a 53–64% decrease in growth of Lewis lung carcinoma for up to a 28-day obser vation period. Polysaccharide supplementation led to an increase in the number of blood cells leukocytes, lymphocytes and phagocytes responsible for antitumor immunity. The chemotherapy in combination with LCS-1269 and polysaccharide had a pronounced sustained antitumor effect on Lewis lung carcinoma in the peripheral blood system of mice in presence of a temporarily increased level of neutrophils and monocytes by the 12th day of tumor development. Apparently, the tested compounds stimulated proliferation of neutrophils and monocytes of certain phenotypes with antitumor activity at an earlier stage of Lewis lung carcinoma de velopment.

Mean and covariance estimation for discretely observed high-dimensional functional data: Rates of convergence and division of observational regimes

Estimation of the mean and covariance parameters for functional data is a critical task, with local linear smoothing being a popular choice. In recent years, many scientific domains are producing multivariate functional data for which p, the number of curves per subject, is often much larger than the sample size n. In this setting of high-dimensional functional data, much of developed methodology relies on preliminary estimates of the unknown mean functions and the auto- and cross-covariance functions. This paper investigates the convergence rates of local linear estimators in terms of the maximal error across components and pairs of components for mean and covariance functions, respectively, in both L2 and uniform metrics. The local linear estimators utilize a generic weighting scheme that can adjust for differing numbers of discrete observations Nij across curves j and subjects i, where the Nij vary with n. Particular attention is given to the equal weight per observation (OBS) and equal weight per subject (SUBJ) weighting schemes. The theoretical results utilize novel applications of concentration inequalities for functional data and demonstrate that, similar to univariate functional data, the order of the Nij relative to p and n divides high-dimensional functional data into three regimes (sparse, dense, and ultra-dense), with the high-dimensional parametric convergence rate of log(p)/n1/2 being attainable in the latter two.

Neural basis of lower-limb visual feedback therapy: an EEG study in healthy subjects

BackgroundVideo-feedback observational therapy (VOT) is an intensive rehabilitation technique based on movement repetition and visualization that has shown benefits for motor rehabilitation of the upper and lower limbs. Despite an increase in recent literature on the neurophysiological effects of VOT in the upper limb, there is little knowledge about the cortical effects of visual feedback therapies when applied to the lower limbs. The aim of our study was to better understand the neurophysiological effects of VOT. Thus, we identified and compared the EEG biomarkers of healthy subjects undergoing lower limb VOT during three tasks: passive observation, observation and motor imagery, observation and motor execution.MethodsWe recruited 38 healthy volunteers and monitored their EEG activity while they performed a right ankle dorsiflexion task in the VOT. Three graded motor tasks associated with action observation were tested: action observation alone (O), motor imagery with action observation (OI), and motor execution synchronized with action observation (OM). The alpha and beta event-related desynchronization (ERD) and event-related synchronization (or beta rebound, ERS) rhythms were used as biomarkers of cortical activation and compared between conditions with a permutation test. Changes in connectivity during the task were computed with phase locking value (PLV).ResultsDuring the task, in the alpha band, the ERD was comparable between O and OI activities across the precentral, central and parietal electrodes. OM involved the same regions but had greater ERD over the central electrodes. In the beta band, there was a gradation of ERD intensity in O, OI and OM over central electrodes. After the task, the ERS changes were weak during the O task but were strong during the OI and OM (Cz) tasks, with no differences between OI and OM.ConclusionAlpha band ERD results demonstrated the recruitment of mirror neurons during lower limb VOT due to visual feedback. Beta band ERD reflects strong recruitment of the sensorimotor cortex evoked by motor imagery and action execution. These results also emphasize the need for an active motor task, either motor imagery or motor execution task during VOT, to elicit a post-task ERS, which is absent during passive observation.Trial Registration NCT05743647

Parathyroidectomy: still the best choice for the management of severe secondary hyperparathyroidism.

Management of secondary hyperparathyroidism (SHPT) is a challenging endeavor with several factors contruibuting to treatment failure. Calcimimetic therapy has revolutionized the management of SHPT, leading to changes in indications and appropriate timing of parathyroidectomy (PTX) around the world. We compared response rates to clinical vs. surgical approaches to SHPT in patients on maintenance dialysis (CKD 5D) and in kidney transplant patients (Ktx). A retrospective analysis of the one-year follow-up findings was carried out. CKD 5D patients were divided into 3 groups according to treatment strategy: parathyroidectomy, clinical management without cinacalcet (named standard - STD) and with cinacalcet (STD + CIN). Ktx patients were divided into 3 groups: PTX, CIN (cinacalcet use), and observation (OBS). In CKD 5D we found a significant parathormone (PTH) decrease in all groups. Despite all groups had a higher PTH at baseline, we identified a more pronounced reduction in the PTX group. Regarding severe SHPT, the difference among groups was evidently wider: 31%, 14% and 80% of STD, STD + CIN, and PTX groups reached adequate PTH levels, respectively (p<0.0001). Concerning the Ktx population, although the difference was not so impressive, a higher rate of success in the PTX group was also observed. PTX still seems to be the best treatment choice for SHPT, especially in patients with prolonged diseases in unresourceful scenarios.

Skeletal Effect of Parathyroidectomy on Patients With Primary Hyperparathyroidism: A Systematic Review and Meta-Analysis.

Parathyroidectomy (PTX) is recommended for curing primary hyperparathyroidism (PHPT), although uncertainty remains regarding the extent of fracture risk reduction following surgery. This work aimed to compare fracture risk and bone mineral density (BMD) changes in patients with PHPT undergoing PTX vs observation (OBS). We systematically searched PubMed, Embase, and the Cochrane Library until September 2022, including randomized controlled trials (RCTs) and cohort studies, and reviewed citations from previous reviews. Among 1260 initial records, 48 eligible articles from 35 studies (5 RCTs; 30 cohorts) included PHPT patients receiving PTX or OBS interventions with reported fracture events at any site, including the hip, spine, or forearm, and/or BMD changes at each location. Data extraction followed Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines by 2 independent reviewers. In 238 188 PHPT patients (PTX: 73 778 vs OBS: 164 410), PTX significantly reduced fractures at any site (relative risk [RR], 0.80; 95% CI, 0.74-0.86) compared to OBS. In 237 217 patients (PTX: 73 458 vs OBS: 163 759), the risk of hip fractures decreased (RR, 0.63; 95% CI, 0.52-0.76). No reduction in forearm and vertebral fractures was observed in 3574 and 3795 patients, respectively. The annual percentage BMD changes from baseline were higher in the PTX group: femoral neck, 1.91% (95% CI, 1.14-2.68); hip, 1.75% (95% CI, 0.58-2.92); radius, 1.75% (95% CI, 0.31-3.18); spine, 2.13% (95% CI, 1.16-3.10). PTX significantly reduced overall and hip fracture risks in PHPT patients. Despite minimal BMD increase, the substantial decrease in fracture risk suggests additional benefits of PTX beyond mineral content enhancement.

High-grade liver injuries with contrast extravasation managed initially with interventional radiology versus observation: A secondary analysis of a WTA multicenter study

BackgroundHigh-grade liver injuries with extravasation (HGLI ​+ ​Extrav) are associated with morbidity/mortality. For low-grade injuries, an observation (OBS) first-strategy is beneficial over initial angiography (IR), however, it is unclear if OBS is safe for HGLI ​+ ​Extrav. Therefore, we evaluated the management of HGLI ​+ ​Extrav patients, hypothesizing IR patients will have decreased rates of operation and mortality. MethodsHGLI ​+ ​Extrav patients managed with initial OBS or IR were included. The primary outcome was need for operation. Secondary outcomes included liver-related complications (LRCs) and mortality. ResultsFrom 59 patients, 23 (39.0%) were managed with OBS and 36 (61.0%) with IR. 75% of IR patients underwent angioembolization, whereas 13% of OBS patients underwent any IR, all undergoing angioembolization. IR patients had an increased rate of operation (13.9% vs. 0%, p ​= ​0.049), but no difference in LRCs (44.4% vs. 43.5%) or mortality (5.6% vs. 8.7%) versus OBS patients (both p ​> ​0.05). ConclusionOver 60% of patients were managed with IR initially. IR patients had an increased rate of operation yet similar rates of LRCs and mortality, suggesting initial OBS reasonable in appropriately selected HGLI ​+ ​Extrav patients.

Pemetrexed (PEM) maintenance versus observation (OBS) in patients (pts) with advanced urothelial carcinoma (aUC) who completed first-line (1L) platinum-based chemotherapy (CTx) without disease progression (PREMIER, KCSG GU16-05).

621 Background: Four-to-six cycles ofplatinum-based CTx have been a standard treatment for aUC. However, disease progresses within several months after completion of 1L CTx. Switch maintenance after 1L with effective and safe regimen is an attractive approach to delay disease progression. PEM showed modest response as a salvage CTx in aUC with mild toxicities, which are good candidate for maintenance therapy. We evaluated PEM as switch maintenance therapy versus OBS in pts with aUC whose disease had not progressed. Methods: Eligible pts with aUC without disease progression after 4-6 cycles of either cisplatin or carboplatin-based regimen were randomized 1:1 to receive maintenance PEM (500 mg/m2 IV q3 weeks, up to 16 cycles) or OBS until disease progression, stratified by Galsky et al.’s post-treatment prognostic nomogram for pts with mUC completing 1L cisplatin-based CTx. The primary endpoint was progression-free survival (PFS), and secondary endpoints included overall survival (OS), response rate, and safety. Results: This trial was closed early due to poor accrual after avelumab maintenance approval. From Oct 2016 to Dec 2022, a total of 97 pts was randomly assigned to maintenance PEM (n=49) or OBS (n=48). Median age (range) was 69 years (43-90) and 66 (33-82), and male was 63% and 73%, respectively. 1L regimen included gemcitabine plus cisplatin (84% and 83%, respectively), gemcitabine plus carboplatin (12% and 6%, respectively), and MVAC (4% and 10%, respectively). Response to 1L were CR (8% vs. 19%), PR (69% vs. 67%), and SD (22% vs. 15%). Most common metastatic site was abdominopelvic lymph nodes (61% and 65%) and lung (37% and 29%). For PEM group, median administered cycle was 6 (range 1-16), and most common reason for discontinuation was disease progression (53%), followed by completion of planned cycles (20%). With a median follow-up of 19.1 months, median PFS was 6.0 months (mo) [95% confidence interval (CI) 3.4-8.5] for PEM vs. 2.3 mo (1.8-2.7) with a log rank p=0.027, with a hazard ratio (HR) of 0.61 (95% CI 0.40-0.95). Median OS was 25.5 mo (95% CI 11.9-30.1) vs. 26.8 (11.9-41.7) (p=0.607, HR 1.18, 95% CI 0.62-2.26). Anemia (29%), fatigue (18%), and neutropenia (12%) were the most frequent adverse events, and these adverse events were mostly grade 1 or 2, and manageable. Conclusions: PREMIER trial showed that switch maintenance PEM prolonged PFS with statistical significance in aUC after 1L platinum-based CTx and had very favorable safety profile. Combination maintenance therapy including PEM needs further investigation. Clinical trial information: NCT03193788 .

Esophagectomy versus observation following endoscopic submucosal dissection of pT1b esophageal adenocarcinoma.

Management following endoscopic submucosal dissection (ESD) of pT1b esophageal adenocarcinoma (EAC) remains controversial. This study compared pathological and survival outcomes of patients after endoscopic resection (ER) of pT1b EAC followed by either en bloc esophagectomy or observation. From 1/12 to 12/22, all patients with pT1b EAC treated with ER were identified from a prospectively maintained departmental database. ESD was curative (all of: Submucosal invasion < 500 μm; G1/2, LVI/PNI-; deep margin-) or non-curative (one or more of Submucosal invasion ≥ 500 μm; G3; LVI/PNI+; deep margin+). Patients were allocated to observation (OBS) or esophagectomy (SURG) based on patient factors/preference and pathological variables. 56/171 ERs met the inclusion criteria. ER was curative in 8/56 (14%) and non-curative in 48/56 (86%). OBS was undertaken after 8/27 (30%) curative and 19/27 (70%) non-curative resections. All 29 SURG patients had non-curative ERs and were younger, had lower Charlson comorbidity scores and had more deep margin + lesions than OBS patients. Post-esophagectomy, 15/29 (52%) had no residual disease within the surgical specimen while pT+N-/pT-N+/pT+N+ occurred in 5/3/6 (17%/10%/21%) patients. Of those with residual disease in the surgical specimen, 12/14 (86%) had deep margin + ERs; however, only ESD instead of EMR was independently associated with a lower risk of residual disease (OR 0.431, 95% CI - 0.016 to 1.234, p = 0.045). OBS and SURG patients had equivalent overall survival outcomes and recurrence was low in both groups even following non-curative ER. Follow-up was 28 months (0-102) and 30 months (0-97), respectively. In select patients, including some of those with a non-curative ESD resection of pT1B EAC, surveillance alone may be appropriate. Alternatives beyond traditional pathological features is needed to direct patient care more accurately.

ВИКОРИСТАННЯ РЕЗУЛЬТАТІВ РОБОТИ МЕТЕОРНОГО АПАРАТУРНО-ПРОГРАМНОГО КОМПЛЕКСУ В ОСВІТНЬОМУ ПРОЦЕСІ ЗІ СТУДЕНТАМИ ФІЗИКО-МАТЕМАТИЧНИХ СПЕЦІАЛЬНОСТЕЙ ЗАКЛАДІВ ВИЩОЇ ОСВІТИ

Features of meteor fixation methods by organizing a network of corresponding observation points – permanently operating observation stations located on the territory of Ukraine with appropriate technical and software for basic and one-way observations of meteors in the radio range of electromagnetic wavelengths are presented, as well as the results of involving students in the analysis of work results meteor hardware and software complex, as a component of the Ukrainian meteor ob servation network. The principle of operation of a separate meteor hardware and softwar e complex for observing meteors in the radio range of electromagnetic waves using the method of direct scattering on meteor trails of signals from powerful FM radio broadcasting stations with the possibility of further processing and presentation of data by students of physical and mathematical specialties of higher education institutions is considered. The results of statistical data processing of meteor invasions and their graphic representation by students of physical and mathematical specialties are described. The seventh reception station in the city of Kyiv (student campus of NUBiP of Ukraine) – the seventh meteor hardware and software complex, as a component of the Ukrainian meteor observation network – has been put into operation.

CMADS and CFSR Data-Driven SWAT Modeling for Impacts of Climate and Land-Use Change on Runoff

Climate and land-use change significantly impact hydrological processes and water resources management. However, studies of runoff simulation accuracy and attribution analysis in large-scale basins based on multi-source data and different scenario projections are limited. This study employed the Soil and Water Assessment Tool (SWAT) model in conjunction with spatial interpolation techniques to evaluate the accuracy of Climate Forecast System Reanalysis (CFSR), China Meteorological Assimilation Driven Dataset (CMADS), and observation (OBS) in runoff simulations, and configured various scenarios using the Patch-generating Land-use Simulation (PLUS) model to analyze effects of climate and land-use changes on runoff in the Jing River Basin from 1999 to 2018. Results demonstrated the superior performance of the CMADS+SWAT model compared to than CFSR+SWAT model, as the latter underestimated peak runoff. Changes in precipitation had a stronger impact on runoff than temperature, with increased flow from farmland and strong interception effects from forestland. Integrated climate and land-use changes led to an average annual runoff reduction of 1.24 m3/s (I2), primarily attributed to climate change (1.12 m3/s, I3), with a small contribution from land-use change (0.12 m3/s, I4). CMADS exhibited robust applicability under diverse scenarios, effectively enhancing runoff simulation accuracy. The findings provide invaluable guidance for water resources management in semi-arid regions.

Candidate germline biomarkers of lenalidomide efficacy in mantle cell lymphoma: the Fondazione Italiana Linfomi MCL0208 trial.

In the Fondazione Italiana Linfomi MCL0208 phase 3 trial, lenalidomide maintenance (LEN) after autologous stem cell transplantation (ASCT) in mantle cell lymphoma (MCL) improved progression-free survival (PFS) vs observation (OBS). The host pharmacogenetic background was analyzed to decipher whether single-nucleotide polymorphisms (SNPs) of genes encoding transmembrane transporters, metabolic enzymes, or cell-surface receptors might predict drug efficacy. Genotypes were obtained via real-time polymerase chain reaction of the peripheral blood germ line DNA. Polymorphisms of ABCB1 and VEGF were found in 69% and 79% of 278 patients, respectively, and predicted favorable PFS vs homozygous wild-type (WT) in the LEN arm was 3-year PFS of 85% vs 70% (P< .05) and 85% vs 60% (P< .01), respectively. Patients carrying both ABCB1 and VEGF WT had the poorest 3-year PFS (46%) and overall survival (76%); in fact, in these patients, LEN did not improve PFS vs OBS (3-year PFS, 44% vs 60%; P= .62). Moreover, the CRBN polymorphism (n= 28) was associated with lenalidomide dose reduction or discontinuation. Finally, ABCB1, NCF4, and GSTP1 polymorphisms predicted lower hematological toxicity during induction, whereas ABCB1 and CRBN polymorphisms predicted lower risk of grade ≥3 infections. This study demonstrates that specific SNPs represent candidate predictive biomarkers of immunochemotherapy toxicity and LEN efficacy after ASCT in MCL.

Observation vs. radiotherapy in primary mediastinal B-cell lymphoma patients with complete response to standard immunochemotherapy: The IELSG37 randomized trial.

LBA7505 Background: Primary mediastinal B-cell lymphoma (PMBCL) has a good prognosis if remission is rapidly achieved with dose‐intensive immunochemotherapy. In these patients mediastinal radiotherapy (RT) may consolidate responses; however, it increases the risk of second malignancies and coronary or valvular heart disease. The IELSG37 trial was planned with a non-inferiority design to test whether RT can be omitted in patients who achieve a complete metabolic response (CMR) after immunochemotherapy. Methods: Patients with newly diagnosed PMBCL were eligible. Initial rituximab and anthracycline-based therapy was chosen according to local practice. CMR was defined, upon central review of positron emission computed tomography (PET/CT) scans, as Deauville score 1 to 3, according to the Lugano classification. Responding patients were randomized to observation (OBS) or consolidation RT (30 Gy). Randomization was stratified on gender, chemotherapy regimen, country, and PET/CT score. The primary endpoint was progression-free survival (PFS) after randomization. The sample size (540 patients to enrol, and 376 to randomize) was calculated assuming a 30-month PFS probability of 0.85 in both arms, with alpha at 0.05, 80% power and a hazard ratio (HR) of 1.77 as non-inferiority margin. Results: At a median follow-up of 30 months, the number of observed events was considerably lower than expected, hence, the Independent Data Monitoring Committee (IDMC) of the trial recommended to complete the planned total accrual without increasing the study size or duration. The primary endpoint analysis was performed, according to the IDMC recommendation, with ≥80% of patients having a minimum follow-up of 30 months. 545 patients (209 men, 336 women) were enrolled. Induction immunochemotherapy was completed and response assessed in 530 patients, 268 of them (50.6%) achieved a CMR and were randomly allocated to OBS (n = 132) or RT (n = 136). The PFS at 30 months was 98.5% (95%CI, 94.3 – 99.6) in the RT arm and 96.2% (95%CI, 91.1-98.4) in the OBS arm (P = 0.278). The estimated relative effect of radiotherapy vs observation in terms of hazard ratio (HR) was 0.47 (0.12-1.89) without adjustments and 0.79 (0.19-3.31) after stratification for the variables used for randomization. At 30 months the absolute risk reduction from RT was 2.3% (-1.5 to 6.2) unadjusted, and 0.8% (-3.0 to 8.3) with stratified HR. The number needed to treat is high (43 patients, unadjusted, and 126 after stratification). The 5-year overall survival was 99% in both arms. Longer follow-up is needed to examine late toxicity. Conclusions: This study is the largest prospective study of PMBCL ever conducted and although the event rate did not reach the assumed level, its evidence supports the omission of RT in patients achieving a CMR after immunochemotherapy.

Sensitivity of WRF multiple parameterization schemes to extreme precipitation event over the Poyang Lake Basin of China

Global warming leads to more frequent and more violent extreme weather events, which cause severe natural disasters. The sensitivity of physical schemes in numerical weather prediction models for extreme precipitation is a significant challenge. To simulate a heavy precipitation process from 1 July 2020 to 10 July 2020 over the Poyang Lake Basin, where floods occur frequently, the Weather Research and Forecast model (WRF) was employed. The observation (OBS) from 92 meteorological stations was applied to evaluate WRF performance. To assess the optimal parameter, 27 combinations of multiphysics schemes based on three cumulus schemes (CUs), three microphysical schemes (MPs) and three land surface schemes (LSMs) were employed in WRF simulation. The Euclid distance (ED) was derived to evaluate the performance of the modelled total cumulative precipitation (TCP). The results showed that the simulation generally reproduced the spatial distribution of precipitation and captured the storm centre. In general, WRF underestimated the observation for most areas but overestimated the observation in the northeastern part of the basin. For total cumulative precipitation (TCP), the spatial correlation coefficients ranged from 0.6 to 0.8. M11 had the highest value of 0.796. The scores (TS, POD, FAR) of M15 were 0.66, 0.79, and 0.21, respectively. With the maximum similarity of 0.518, M7 (BMJ-WDM6-Noah) showed the best performance in ED based on six evaluation metrics. The mean values of OBS and M19 were 259.34 and 218.33 mm, respectively. M19 (NT-Thompson-Noah) was closest to the OBS for the range of the TCP. In terms of daily precipitation, the CC of M3 was maximum (0.96), and the RMSE of M24 was minimum (11.9 mm. day-1). The minimum error between the simulation and OBS was found for M3 (NT-Thompson-Noah). Therefore, with a comprehensive evaluation, five optimal combinations of physical schemes (M22, M19, M9, M3, M21) were found for the PLB, which is of great significance for extreme precipitation simulation and flood forecasting.

A randomized, phase II trial of oral azacitidine (CC-486) in patients with resected pancreatic adenocarcinoma at high risk for recurrence

BackgroundOf the only 20% of patients with resectable pancreatic ductal adenocarcinoma (rPDA), cancer recurs in 80% of cases. Epigenetic dysregulation is an early hallmark of cancer cells acquiring metastatic potential, and epigenetic modulators may reactivate tumor suppressor genes, delay recurrence, and sensitize PDA to future chemotherapy.MethodsThis was a randomized phase II study (NCT01845805) of CC-486 (oral DNA methyltransferase inhibitor azacitidine) vs. observation (OBS) in rPDA patients harboring high-risk features (stage pN1-2, R1 margins, or elevated CA 19–9 level) with no evidence of disease following standard adjuvant therapy. Patients were randomized to oral CC-486 treatment (300 mg daily on days 1–21 on a 28-day cycle) or OBS for up to 12 cycles or until disease relapse/unacceptable toxicities. Following recurrence, records of next-line therapies, imaging, and survival were obtained. The primary endpoint was progression-free survival (PFS)—time from randomization to recurrence (imaging/biopsy confirmed or death). Secondary endpoints included OS and PFS and ORR and metastatic PFS with subsequent next-line systemic therapy in metastatic setting.ResultsForty-nine patients (24 in CC-486 arm, 25 in OBS arm) were randomized: median age 66 (range 36–81), 53% male, 73% node positive, 49% elevated CA 19–9, 20% R1 resection, 63% and 100% received perioperative concurrent chemoradiation and chemotherapy, respectively. Median time from surgery to randomization was 9.6 mo (range 2.9–36.8). For the CC-486 arm, median treatment duration was 5.6 mo (range 1.3 to 12.8) with 14 treatment-related grade 3 or 4 AEs among 5 patients (22%) resulting in dose-reduction. Four patients (17%) discontinued therapy due to AEs. With median follow-up of 20.3mo (IQR 12.8, 41.4), 38 (79%) of evaluable patients recurred (34 imaging-confirmed, 4 clinically). Median PFS in imagining-confirmed cases was 9.2 and 8.9mo (HR 0.94, 95% CI 0.46–1.87, p = 0.85) for CC-486 and OBS patients, respectively. Median OS (2-yr OS%) was 33.8 (50%) and 26.4 mo (61%) in CC-486 and OBS patients, respectively. (HR 0.98, 95% CI 0.46–2.05, p = 0.96). ORR with subsequent chemotherapy in the metastatic setting was minimal in both arms.ConclusionsTreatment with CC-486 following adjuvant therapy did not prolong time-to-relapse in patients with high-risk rPDA or improve disease response on 1st-line metastatic therapy.

Lymph Node Metastasis Spread Patterns and the Effectiveness of Prophylactic Neck Irradiation in Sinonasal Squamous Cell Carcinoma (SNSCC).

ObjectivesTo analyze the incidence and spread of lymph node metastasis (LNM) and the effectiveness of prophylactic neck irradiation in patients with SNSCC.MethodsA total of 255 patients with SNSCC were retrospectively reviewed. The LNM spread pattern was revealed. The clinical parameters related to LNM, and the prognostic value of elective neck irradiation (ENI) were assessed. A 1:1 matching with propensity scores was performed between ENI group and observation (OBS) group.ResultsThe initial LNM rate was 20.8%, and the regional recurrence (RR) rate was 7.5%. Lymphatic spreading in SNSCC followed the common trajectories: a. level Ib ➔ level II ➔ level Va/level III/IV lymph nodes (LNs); b. retropharyngeal lymph nodes (RPLNs) ➔ level II LNs. The most frequently involved site was level II LNs (16.1%), followed by level Ib LNs (10.2%), RPLNs (4.7%), level III LNs (3.2%), level Va LNs (1.6%), level IVa LNs (1.4%) and level VIII LNs (0.8%). The median follow-up time was 105 months. The 5-year overall survival (OS) was 55.7% for N0 patients and 38.5% for patients with initial N+ or N- relapse (p = 0.009). After PSM, the 5-year regional recurrence-free survival was 71.6% and 94.7% (p = 0.046) in OBS and ENI group, respectively. The multivariate analysis showed that ENI (p = 0.013) and absence of nasopharynx involvement (p = 0.026) were associated with a significantly lower RR rate.ConclusionsPatients with LNM had poorer survival than those who never experienced LNM. Lymphatic spread in SNSCC followed predictable patterns. ENI effectively reduced the RR rate in patients at high risk.

Evaluation of Sea Ice Concentration Data Using Dual-Polarized Ratio Algorithm in Comparison With Other Satellite Passive Microwave Sea Ice Concentration Data Sets and Ship-Based Visual Observations

The dual-polarized ratio (DPR) algorithm is a new algorithm that enable calculation of Arctic sea ice concentration from the 36.5-GHz channel of the sensor Advanced Microwave Scanning Radiometer for EOS/Advanced Microwave Scanning Radiometer 2 (AMSR-E/AMSR2). In this paper, we demonstrate results that the sea ice concentration data using DPR algorithm (DPR-AMSR) are evaluated and compared with other eight Arctic sea ice concentration data products with respect to differences in sea ice concentration, sea ice area, and sea ice extent. On a pan-Arctic scale, the evaluation results are mostly very similar between DPR-AMSR and the bootstrap algorithm from AMSR-E/AMSR2 (BT-AMSR), the bootstrap algorithm from SSM/I or SSMIS (BT-SSMI), the ARTIST Sea Ice algorithm from AMSR-E/AMSR2 (ASI-AMSR), and the enhanced NASA Team algorithm from AMSR-E/AMSR2 (NT2-AMSR). Among of these products, the differences in sea ice concentration agree within ±5%. However, European Space Agency Climate Change Initiative algorithm from AMSR-E/AMSR2 (SICCI-AMSR), the European Organisation for the Exploitation of Meteorological Satellites Ocean and Sea Ice Satellite Application Facility from SSM/I or SSMIS (OSI-SSMI), the ARTIST Sea Ice algorithm from SSM/I or SSMIS (ASI-SSMI), and the NASA Team algorithm from SSM/I or SSMIS (NT1-SSMI) are all lower than DPR-AMSR at sea ice edge. And NT1-SSMI had the largest negative difference, which was lower than -15% or even 20%.The difference of sea ice area was consistently within ±0.5 million km2 between DPR-AMSR and BT-AMSR, BT-SSMI, ASI-AMSR, and NT2-AMSR in all years. The smallest difference was with BT-SSMI (less than 0.1 million km2), whereas the largest difference was with NT1-SSMI (up to 1.5 million km2). In comparisons of sea ice extent, BT-AMSR, NT1-SSMI, and NT2-AMSR estimates were consistent with that of DPR-AMSR and were within ±0.5 million km2. However, differences exceeded 0.5 million km2 between DPR-AMSR and the other data sets. When ship-based visual observation (OBS) values ranged from 85% to 100%, the difference between DPR-AMSR and OBS was less than 1%. There were relatively large differences between DPR-AMSR and OBS when OBS values were less than 85% or were recorded during the summer, although those differences were also within 10%.

Is adjuvant chemotherapy necessary for young women with early-stage epithelial ovarian cancer who have undergone fertility-sparing surgery?: a multicenter retrospective analysis

ObjectiveIn young patients with early-stage epithelial ovarian carcinoma (EOC) who were received fertility-sparing surgery (FSS), the role of adjuvant chemotherapy is unclear. Here, we performed a multicenter study using inverse probability of treatment weighting (IPTW) to explore the effect of chemotherapy on patients’ survival.MethodsBetween 1987 and 2015, a retrospective study was carried out, including 1183 patients with stage I EOC. Among them, a total of 101 women with stage I EOC who underwent FSS were investigated, including 64 and 37 patients with or without adjuvant chemotherapy, respectively. Oncologic outcomes were compared between the two arms using original and IPTW cohorts.ResultsDuring 62.6 months (median) of follow-up, recurrence was noted in 11 (17.2%) women in the chemotherapy arm and 6 (16.2%) patients in the observation arm. In the unweighted cohort, the 5-year overall and recurrence-free survival (OS/RFS) rates of chemotherapy and observation arms were 86.3/80.8 and 90.2/79.8%, respectively. There was no significant difference between the two groups {Log-rank: P = 0.649 (OS)/P = 0.894 (RFS)}. In the IPTW cohort after adjusting for various clinicopathologic covariates, we also failed to identify a difference in RFS/OS between the two groups {RFS (chemotherapy vs. observation), HR: 0.501 (95% CI 0.234–1.072), P = 0.075: OS (chemotherapy vs. observation), HR: 0.939 (95% CI 0.330–2.669), P = 0.905}.ConclusionsEven after adjusting clinicopathologic covariates, performing adjuvant chemotherapy may not improve the oncologic outcome in young patients who have undergone FSS.

Neck Management in cT1N0 Tongue Squamous Cell Carcinoma as Determined by Sonographic Depth of Invasion.

ObjectivesTo compare the oncologic outcomes in patients with cT1N0 tongue squamous cell carcinoma (SCC) who underwent different neck management strategies stratified by sonographic depth of invasion (DOI).MethodsThe included patients were retrospectively enrolled, and divided into two groups: observation (OBS) and elective neck dissection (END). The regional control (RC) and disease-specific survival (DSS) rates were compared and stratified by sonographic DOI.ResultsThe mean sonographic and pathologic DOIs were 3.8 and 3.7 mm, respectively; the two DOIs were significantly correlated (Spearman correlation coefficient 0.974. p <0.001). In patients with sonographic DOI <4.0 mm, the 5-year RC rates were 73 and 89% in the OBS and END groups, respectively, and were not significantly different. However, in patients with sonographic DOI ≥4.0 mm, the 5-year RC rate was significantly different between the OBS (57%) and END (80%) groups (p = 0.031). In patients with sonographic DOI <4.0 mm, the 5-year DSS rates were 79 and 89% in OBS and END groups, respectively, and were not significantly different. However, in patients with sonographic DOI ≥4.0 mm, the 5-year DSS rate was significantly different between the OBS (67%) and END (86%) groups (p = 0.033).ConclusionsSonographic DOI was notably correlated with pathologic DOI. Moreover, there was a significant survival difference between the OBS and END groups in cT1N0 tongue SCC patients with sonographic DOI ≥4.0 mm but not in those with sonographic DOI <4.0 mm. Our study provides a useful method to aid decision-making in the clinical setting for this patient group.

Controversial benefit of 5-fluorouracil/leucovorin-based adjuvant chemotherapy for ampullary cancer: a propensity score-matched analysis.

Although surgery is the primary treatment for ampullary cancer (AC), the benefit of adjuvant chemotherapy (CTx) has not yet been confirmed. AC patients who were administered 5-fluorouracil(FU)/leucovorin(LV)-based CTx after curative intent surgery between 2011 and 2019 were included. Prognosis was compared between the observation (OB) and CTx groups after propensity score matching (PSM) using perioperative variables to control differences in patient characteristics. Before PSM, of 475 patients, those in the CTx group (n = 281) had worse 5-year overall survival (OS) (82.1% vs. 78.5%, p = 0.017) and worse 5-year recurrence-free survival (RFS) (54.9% vs. 75.7%, p < 0.001) than those in the OB group (n = 194). In addition, the CTx group had a higher rate of poor prognostic factors such as a high T stage (p < 0.001), node metastasis (p < 0.001), and poor differentiation (p < 0.001). After PSM, perioperative outcomes were comparable. In addition, there were no significant differences in OS (hazard ratio [HR], 1.085; 95% confidence interval [CI], 0.688-1.710; p = 0.726) or RFS (HR, 0.883; 95% CI, 0.613 1.272; p = 0.505) between the CTx (n = 123) and OB (n = 123) groups even after stratification by TNM stage. Intestinal subtype showed better 5-year OS (83.7% vs 33.2%, p = 0.015) and RFS (46.5% vs 24.9%, p = 0.035) rate compared with pancreatobiliary/mixed subtype. Patients who received adjuvant chemotherapy based on 5-FU/LV showed comparable oncologic outcomes to patients in the OB group even after stratification by tumor stage. The patients with intestinal subtype showed oncologic benefit for adjuvant 5-FU/LV CTx compared with pancreatobiliary or mixed subtypes.

Elective Neck Dissection Versus Therapeutic Neck Dissection in Clinically Node-Negative Early Stage Oral Cancer: A Meta-analysis of Randomized Controlled Trials.

Oral squamous cell carcinoma (OSCC) is characterized by a high risk of cervical lymph node metastasis; however, it is still not clear whether patients with early stage OSCC with clinical N0 neck should undergo elective neck dissection (END) at the time of primary tumor removal, or they should undergo a conservative approach of observation (OBS), with therapeutic neck dissection at the time of lymph nodal recurrence. We conducted a meta-analysis of randomized controlled trials (RCTs) that compared these two approaches. PubMed and Scopus databases were searched for RCTs published in English language related to END and OBS in patients with early stage OSCC with clinical N0 neck. A meta-analysis was performed using random effects model with hazard ratio (HR) as the effect size for survival parameters and odds ratio (OR) as the effect size for lymph nodal recurrence. A total of 7 RCTs, comprising 1250 patients were included in the meta-analysis. Results of the meta-analyses showed that as compared to OBS approach, END could significantly improve overall survival (HR 0.67; 95% CI 0.53, 0.86) and disease-free survival (HR 0.64; 95% CI 0.46, 0.89), and significantly reduce lymph nodal recurrence (OR 0.28; 95% CI 0.12, 0.66). After correcting for heterogeneity, the disease specific survival was also found to be improved by the END approach (HR 0.53; 95% CI 0.29, 0.98). The results of this meta-analysis suggest that elective neck dissection at the time of resection of the primary tumor not only leads to a reduced chance of nodal recurrence, but also confers a survival benefit in patients with clinically node-negative early stage oral cancer.