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The PROpel trial assessed the combination of olaparib+abiraterone acetate (AA) plus prednisone and androgen deprivation therapy (ADT) versus AA plus prednisone and ADT alone as first-line treatment for metastatic castration-resistant prostate cancer (mCPRP). To contextualize the progression free survival (PFS) benefit in PROpel, we performed a systematic review and quasi-individual patient data network meta-analysis on randomized controlled trials of first-line hormonal treatments for mCPRC. Meta-analysis was performed for the PROpel control arm and PREVAIL (enzalutamide) and COU-AA-302 (AA) treatment arms. Kaplan-Meier PFS curves were digitally reconstructed and differences in restricted mean survival time (ΔRMST) were computed. Combination therapy yielded longer PFS (24-mo ΔRMST 1.5 mo, 95% confidence interval 0.6-2.4) in comparison to novel hormonal treatments alone. However, the lack of mature overall survival data, higher complication rates, and higher health care costs are limitations of combination therapy. Ultimately, combining treatments, rather than molecularly targeted sequencing in cases of failure, might not be justified in unselected patients with mCRPC.Patient summaryA recent trial showed that for metastatic prostate cancer that does not respond to hormone treatment, combined therapy with two drugs (olaparib and abiraterone) may prolong survival free from cancer progression. We included these data in an analysis of three trials that confirmed a small benefit. This combination approach has higher complication rates and is more expensive, and longer-term results for overall survival are needed.

Background Elevated serum progranulin (PGRN) levels have been associated with a wide range of different human malignancies. However, data available on the role of PGRN in hematological malignancies are limited. Methods Measurement of the PGRN level in serum of adult de novo acute myeloid leukemia (AML) patients using enzyme-linked immunosorbent assay (ELISA) was performed. Results The mean serum PGRN level in AML patients was higher than that in controls (346.08 pg/ml ± 64.46 vs 155 pg/ml ± 63 respectively; p = 0.001). After a mean duration of follow-up equaling 140 days, patients with high serum PGRN (i.e., higher than 370.5 pg/ml) had inferior overall survival (OS) in comparison to patients with low serum PGRN (i.e., lower than 370.5 pg/ml) (OS = 25% vs 60.7%, mean survival = 107 days vs 256.5 days, p = 0.007). On the other hand, remitted patients on day 28 with high serum PGRN (i.e., higher than 307.5 pg/ml) did not differ from those with low serum PGRN (i.e., lower than 307.5 pg/ml) regarding disease-free survival (DFS) (DFS = 78.6% vs. 87.5%, mean survival = 301.3 days vs. 283.5 days, p = 0.789). Moreover, the serum PGRN level was associated with inferior OS (p = 0.024) on multivariate analysis. Conclusion Adult de novo AML patients have elevated serum PGRN levels and a high PGRN level is associated with an inferior OS.

Resumen Objetivos La mayoria de los ensayos clinicos realizados sobre pacientes con cancer escamoso anal (CEA) excluyen pacientes inmunodeprimidos. El objetivo del presente estudio es comparar las caracteristicas y los resultados oncologicos entre pacientes con CEA inmunocomprometidos e inmunocompetentes. Metodos Estudio multicentrico comparativo retrospectivo que incluye 2 cohortes consecutivas de pacientes, inmunocomprometidos e inmunocompetentes, diagnosticados de carcinoma escamoso anal. Se han investigado las caracteristicas de los pacientes, los tratamientos realizados, la respuesta clinica al tratamiento con quimiorradioterapia (QRT), la recidiva local o a distancia, la supervivencia global (SG) y la supervivencia libre de enfermedad (SLE). Resultados De enero 2012 a diciembre 2017 hemos estudiado a 84 pacientes, 47 (55,6%) mujeres, afectos de CEA, de los cuales 22 (26%) han sido pacientes inmunocomprometidos y 62 (74%) inmunocompetentes. Los pacientes inmunocomprometidos fueron mas jovenes (53 vs. 61 anos; p = 0,001), con un menor tamano tumoral (p = 0,044), y presentaban un mayor consumo de tabaco (p = 0,034) y de drogas de uso parenteral (p = 0,001). No se objetivaron diferencias significativas en los tratamientos administrados (p = 0,301), tampoco difirio la respuesta clinica a la QRT (83 vs. 100%). Tampoco se observaron diferencias significativas en la supervivencia global (60 vs. 64%; p = 0,756) o en la supervivencia libre de enfermedad a 5 anos (SLE) (65 vs. 68%; p = 0,338). Conclusiones En el presente estudio no se observaron diferencias significativas en relacion con los resultados oncologicos a largo plazo entre pacientes inmunocompetentes e inmunocomprometidos diagnosticados de CEA, con un grado de cumplimiento del tratamiento similar. Esta evidencia podria deberse al estrecho seguimiento y buen control terapeutico de pacientes infectados por HIV.

To assess the patterns and time trends in overall survival and progression-free survival treatment effects across randomized controlled trials (RCTs) in oncology.A PubMed search for oncology network meta-analyses (NMAs) was carried (to September 30, 2021). Relevant hazard ratios were extracted for systemic treatments from RCTs in the NMAs. After removing duplicate results, relationships between treatment effects, year of publication, trial design, and other features were explored.From 241 oncology NMAs, 2,109 unique eligible RCTs provided analyzable data. On average, there was a 12%-14% reduction in hazard for overall survival and 27%-30% reduction for progression-free survival, with substantial heterogeneity across different malignancies. Correlation between overall survival and progression-free survival treatment effects was modest (r = 0.60, 95% confidence interval, 0.56-0.64). Over time, there was a suggestive trend of increased progression-free survival treatment effect, although overall survival treatment effects remained steady. Only one in five trials met criteria for clinically meaningful improvements in overall survival. Among 300 randomly selected trials, mean absolute improvement was 1.6 months for median progression-free survival and 1.4 months for median overall survival.Broad patterns across the past 50 years of oncology research suggest continuous progress has been made, but few results meet clinically meaningful thresholds for overall survival improvement.

[Background] Neoadjuvant immunotherapies hold promise in muscle-invasive bladder cancer (MIBC)., [Objective] To report on 2-yr disease-free (DFS) and overall (OS) survival including novel tissue-based biomarkers and circulating tumor DNA (ctDNA) in the ABACUS trial., [Design, setting, and participants] ABACUS was a multicenter, single-arm, neoadjuvant, phase 2 trial, including patients with MIBC (T2-4aN0M0) who were ineligible for or refused neoadjuvant cisplatin-based chemotherapy., [Intervention] Two cycles of atezolizumab were given prior to radical cystectomy. Serial tissue and blood samples were collected., [Outcome measurements and statistical analysis] The primary endpoints of pathological complete response (pCR) rate and dynamic changes to T-cell biomarkers were published previously. Secondary outcomes were 2-yr DFS and OS. A biomarker analysis correlated with relapse-free survival (RFS) was performed, which includes FOXP3, major histocompatibility complex class I, CD8/CD39, and sequential ctDNA measurements., [Results and limitations] The median follow-up time was 25 mo (95% confidence interval [CI] 25–26). Ninety-five patients received at least one cycle of atezolizumab. Eight patients did not undergo cystectomy (only one due to disease progression). The pCR rate was 31% (27/88; 95% CI 21–41). Two-year DFS and OS were 68% (95% CI 58–76) and 77% (95% CI 68–85), respectively. Two-year DFS in patients achieving a pCR was 85% (95% CI 65–94). Baseline PD-L1 and tumor mutational burden did not correlate with RFS (hazard ratio [HR] 0.60 [95% CI 0.24–1.5], p = 0.26, and 0.72 [95% CI 0.31–1.7], p = 0.46, respectively). RFS correlated with high baseline stromal CD8+ (HR 0.25 [95% CI 0.09–0.68], p = 0.007) and high post-treatment fibroblast activation protein (HR 4.1 [95% CI 1.3–13], p = 0.01). Circulating tumor DNA positivity values at baseline, after neoadjuvant therapy, and after surgery were 63% (25/40), 47% (14/30), and 14% (five/36), respectively. The ctDNA status was highly prognostic at all time points. No relapses were observed in ctDNA-negative patients at baseline and after neoadjuvant therapy. The lack of randomization and exploratory nature of the biomarker analysis are limitations of this work., [Conclusions] Neoadjuvant atezolizumab in MIBC is associated with clinical responses and high DFS. CD8+ expression and serial ctDNA levels correlated with outcomes, and may contribute to personalized therapy in the future, [Patient summary] We showed that bladder cancer patients receiving immunotherapy followed by cystectomy have good long-term outcomes. Furthermore, we found that certain biological features can predict patients who might have particular benefit from this therapy., Bernadett Szabados—research funding from MSD and Roche; honoraria from Roche, MSD, and BMS. Mark Kockx—employee of CellCarta. Zoe June Assaf—employee of Roche. Pieter-Jan van Dam—employee of CellCarta. Alejo Rodriguez-Vida—research funding and honoraria from Roche, BMS, and Pfizer; research funding from Novartis and Astellas. Ignacio Duran—research funding and honoraria from Roche, BMS, Pfizer, and Johnson & Johnson; research funding from Astellas. Simon J. Crabb—research funding and honoraria from Roche, MSD, Pfizer, Exelixis, and Clovis. Michiel S. Van Der Heijden—research funding and honoraria from BMS, AstraZeneca, MSD, Novartis, Pfizer, MSD, and Seattle Genetics. Albert Font Pous—research funding and honoraria from MSD, Pfizer, and Astellas. Gwenaelle Gravis—research funding and honoraria from Roche, AstraZeneca, Pfizer, and Astellas. Urbano Anido Herranz—research funding and honoraria from Roche, MSD, Exelixis, and Astellas. Andrew Prothoroe—research funding and honoraria from Astellas, Pfizer, Novartis, and BMS. Alain Ravaud—research funding and honoraria from MSD, Roche, BMS, and Pfizer. Denis Maillet—research funding and honoraria from MSD and Roche. Maria Jose Mendez—research funding and honoraria from Roche and Pfizer. Cristina Suarez—research funding and honoraria from Pfizer, BMS, Roche, AstraZeneca, and Astellas. Mark Linch—research funding and honoraria from BMS, Roche, Pfizer, Astellas, and AstraZeneca. Aaron Prendergast and Charlotte Tyson—no conflicts. Diana Stanoeva, Sofie Daelemans, and Miche Rombouts— employee of CellCarta. Sanjeev Mariathasan—employee of Genentech. Joy S. Tea—employee of Roche. Kelly Mousa—no conflicts. Romain Banchereau—employee of Genentech. Daniel Castellano—research funding and honoraria from Astellas, BMS, Roche, and AstraZeneca. Thomas Powles—honoraria from AstraZeneca, BMS, Exelixis, Incyte, Ipsen, Merck, MSD, Novartis, Pfizer, Seattle Genetics, Merck Serono, Astellas, Johnson & Johnson, Eisai, and Roche; research funding from AstraZeneca, BMS, Exelixis, Ipsen, Merck, MSD, Novartis, Pfizer, Seattle Genetics, Merck Serono, Astellas, Johnson & Johnson, Eisai, and Roche; travel/accommodation/expenses from Roche, Pfizer, MSD, AstraZeneca, and Ipsen.

Background: Cisplatin is preferred to carboplatin when treating metastatic urothelial carcinoma of the bladder (mUCB), despite its greater toxicity. Randomised studies underpinning this have been performed in noncontemporary populations with limitations in sample sizes and analyses, affecting their validity in current clinical practice. Objective: To estimate overall survival (OS) and assess the benefit of cisplatin-based regimens over carboplatin-based regimens in a contemporary cohort of patients with mUCB. Design, setting, and participants: A nationwide retrospective cohort study was conducted in patients diagnosed with de novo mUCB in the Netherlands between 2016 and 2019, who underwent first-line treatment with cisplatin- or carboplatin-based chemotherapy, based on the data from the Netherlands Cancer Registry. Outcome measurements and statistical analysis: A propensity model for receiving cisplatin-based chemotherapy based on age, sex, age-adjusted Charlson Comorbidity Index, renal function, performance status, serum haemoglobin, and the presence of visceral and bone metastases was used to produce inverse probability weighting (IPW) per patient. Unadjusted and IPW-adjusted Kaplan-Meier OS curves of both chemotherapy groups were compared by restricted mean survival time (RMST). Results and limitations: Of the 1041 patients with mUCB, 359 received either cisplatin (n = 170; 47%) or carboplatin (n = 189; 53%) as first line. The cisplatin group was younger, had fewer comorbidities, and had better performance status and renal function. The median OS in the cisplatin and carboplatin groups was 13.1 and 11.5 mo, respectively. After IPW adjustment, prognostic factors were balanced between the two chemotherapy groups (standardised differences

There have been no prior studies examining the effect of distance to the treatment centre on oral squamous cell carcinoma outcomes in Australia. The purpose of this study was to analyse the impact of travel distance on oral tongue squamous cell carcinoma (OTSCC) outcomes. This was a retrospective analysis of 243 patients who received surgical treatment ± adjuvant therapy between 2007 and 2016. The overall survival (OS), disease-specific survival (DSS), and freedom from loco-regional failure (FFLRF) survival analyses were conducted using Kaplan-Meier curves and a multivariate Cox proportional hazards model. A competing risk (CR) analysis was conducted. Patients living ≥200 km from the treatment centre, when compared with those living within 40 km, had worse OS (hazard ratio (HR) 3.11, 95% confidence interval (CI) 1.74-5.54), DSS (HR 2.58, 95% CI 1.30-5.12), and FFLRF (HR 2.47, 95% CI 1.22-5.01). These discrepancies were significant when adjusted for socioeconomic status (OS P

Introduction Progression of carcinoid syndrome (CS) to carcinoid heart disease (CHD) is difficult to predict. This retrospective analysis evaluates the use of chromogranin A (CgA), a biomarker widely used in the diagnosis of neuroendocrine tumours (NET), in monitoring CS and disease progression. Patients and methods 108 patients with confirmed CS, selected from a group of 351 patients with neuroendocrine neoplasms of the small intestine (SI-NENs), including NETG1 well 40% and NETG2 60% moderately differentiated NET. CgA concentration was measured during initial diagnosis and clinical follow up in 84 patients, 27 of them subsequently developed CHD. The patient's overall survival (OS) was evaluated using the Kaplan-Meier method. Results Patients with CHD, were found to have significantly shorter OS than patients with CS but without CHD (67.22 vs. 73.03 months). Univariate and multivariate analyses revealed that initial high concentration of CgA and/or increased concentration of CgA is significantly associated with decreased median OS in patients with CS (p Conclusion CgA has potential as a clinically useful biomarker in reporting disease status and predicting outcome in patients with CS and with CHD.

Background We present here a case series of patients who underwent resection for Masaoka Stage III and IVa Thymic Epithelial Tumors (TETs) with invasion into the superior vena cava. Methods 29 patients with Stage III and IVa TETs were treated surgically in three institutions. Operative resections involved replacing the superior vena cava from one of the innominate veins (n=18) or via reconstruction by truncal replacement (n=2) or patchplasty (n=9). Results Fifteen patients underwent neoadjuvant treatment. Thirty and 90-day mortality rate were 3.4% and 10.3%, respectively. For Stage III patients, the median overall survival and DFS were 39 and 30 months, respectively. The median overall survival and DFS in patients with Masaoka Stage IVa disease were 67 and 21 months, respectively. Undergoing only preoperative chemotherapy (p=0.007) or receiving no chemotherapy (p=0.009) had a disease-free survival that was significantly higher than receiving both pre- and postoperative chemotherapy. Conclusions SVC resection and reconstruction in Masoaka Stage III and IVa TETs can be performed with acceptable morbidity and mortality. Stage IVa patients with SVC involvement can be treated with similar results as Stage III patients with multimodality treatment.

Background Data regarding Asian patients with mycosis fungoides (MF) are limited. Objective We aimed to investigate the clinical profile and long-term outcomes of patients with MF in Korea. Methods A retrospective review of 223 patients with MF who were followed up for more than 6 months or died of MF within 6 months of diagnosis was performed. Results Approximately 96.4% and 3.6% of the patients had an early stage and advanced stage, respectively. The mean age at diagnosis was 44.8 years. The mean duration of symptoms before diagnosis was 47.0 months. Various subtypes were noted, including mycosis fungoides palmaris et plantaris (21.5%), folliculotropic (8.5%), pityriasis lichenoides-like (6.7%), ichthyosiform (4.0%), lichenoid purpura-like (2.7%), and hypopigmented (2.2%) MF. Juvenile patients accounted for 16.6%. The higher the skin T stage, the poorer the response to treatment. The 10-year overall survival was 96.8% in early-stage patients and 25.0% in advanced-stage patients. General prognosis was favorable, while recurrence and subtype switching were seen in 29.4% and 2.7% of patients, respectively. Limitations Our patients may not represent all Korean patients with MF. Conclusion MF in Korea has a high proportion of variants, a younger age at onset, and favorable prognosis. A high index of suspicion and skin biopsy are needed for early diagnosis.

BACKGROUND Higher-volume centers for pancreatic cancer surgeries have been shown to have improved outcomes such as length of stay. We examined how centralization of pancreatic cancer care within a regional integrated healthcare system improves overall survival. METHODS We conducted a retrospective study of 1621 patients treated for pancreatic cancer from February 2010 to December 2018. Care was consolidated into 4 Centers of Excellence (COE) in surgery, medical oncology, and other specialties. Descriptive statistics, bivariate analysis, Chi-square tests, and Kaplan-Meier analysis were performed. RESULTS Neoadjuvant chemotherapy use rose from 10% to 31% (p

The optimal minimally invasive surgical approach to mediastinal tumors is unknown. There are limited reports comparing the outcomes of resection with robotic-assisted thoracoscopic surgery (RATS) and video-assisted thoracoscopic surgery (VATS) surgery. We hypothesized that patients who underwent RATS would have improved outcomes.The National Cancer Database was queried for all patients who underwent a minimally invasive surgical approach for any mediastinal tumor from 2010 to 2016. Patients were determined to have an adverse composite outcome if they had any of the adverse perioperative outcomes: conversion to open procedure, 90-day mortality, 30-day readmission, and positive pathologic margins. Secondary outcomes of interest were length of stay and overall survival. Multivariable logistic regression was used to assess likelihood of having a composite adverse outcome based on surgical approach.The study included 856 patients: 402 (47%) underwent VATS and 454 (53%) underwent RATS. RATS resections were associated with fewer conversions (4.9% vs 14.7%, P.001), fewer positive margins (24.3% vs 31.6%, P = .02), shorter length of stay (3.8 days vs 4.3 days, P = .01), and fewer composite adverse events (36.7% vs 51.3%, P.001). Multivariate analysis showed RATS (odds ratio, 0.44; P.001) was independently associated with a decreased likelihood of a composite adverse outcome, even among tumors exceeding 4 cm (odds ratio, 0.45; P = .001). Overall survival was similar between the 2 groups.Among patients who underwent a minimally invasive surgical approach for a mediastinal tumor, RATS had fewer adverse outcomes than VATS, even for tumors 4 cm or larger. These data suggests that RATS may be the preferred technique for patients who are candidates for minimally invasive resection of mediastinal tumors.

Summary Background /Objective: As a new immune-nutritional marker, the controlled nutritional status (CONUT) score has been reported to predict the prognosis of cancer patients. We aimed to elucidate the prognostic value of preoperative CONUT score in pancreatic cancer patients undergoing radical surgery, and to construct a nomogram based on CONUT score to predict individual survival. Methods Preoperative CONUT scores were calculated prospectively in 382 patients with pancreatic cancer who underwent radical surgery. Evaluated the relationship between CONUT score and pancreatic cancer prognosis. Cox proportional hazard models were used to determine predictors of survival and a new nomogram was established to predict pancreatic cancer overall survival (OS). Results The area under curve of CONUT score was higher than other immune-nutritional indexes. The OS of the high-CONUT group were significantly lower than that of low-CONUT group. Multivariate analysis showed that CONUT score, gender, AJCC stage, complications and reoperation were independent prognostic factors for OS. Nomogram based on these variables has better discriminant ability in predicting survival compared with other traditional staging systems. Conclusions Preoperative CONUT score is an effective independent predictor of OS in pancreatic cancer patients undergoing radical surgery. This new CONUT based nomogram provides accurate, individualized survival prediction for pancreatic cancer.

Background Little is known about the influence of hepatic artery infusion pump (HAIP) therapy in the setting of chemotherapy resistant hepatic disease in the era of modern systemic therapies. Methods Patients who underwent HAIP therapy for chemotherapy resistant and unresectable colorectal liver metastases (CRLM) were reviewed retrospectively. Results A total of 25 patients met inclusion criteria. 52% had isolated CRLM and 92% had five or more metastatic lesions. Partial response was noted in 40% of patients. Median hepatic progression-free survival (PFS) was 7 months in those with extrahepatic disease versus 6 months in those with isolated CRLM at the time of HAIP placement (p = 0.75). Median overall survival was 8 months in patients with extrahepatic disease and 14 months in patients with isolated CRLM (p = 0.06). Conclusions Our findings are comparable to published data and augment the literature which supports HAIP use in chemotherapy-resistant, liver-predominant metastatic colorectal cancer patients.

Aim This study aimed to assess the impact of treatment sequencing on long-term survival, in distal gastric cancers (GCs) (stage IB/II/III). Methods This retrospective study included patients with distal GC undergoing D2 resection. Outcomes were compared between group 1 (surgery with adjuvant chemotherapy) and group 2 (perioperative chemotherapy with surgery). 1:1 matching for baseline characteristics (age, cT, and cN stage) was performed for outcome comparison. Results At a median follow-up of 47.5 months in the included 342 patients, the 5-year overall survival (OS) was 61.1% and disease-free survival (DFS) was 50.5%. OS was comparable in the unmatched (group 1, n = 118; group 2, n = 224) (HR 0.905, 95%CI 0.64–1.33, P = 0.615) and matched groups (group 1, n = 97; group 2, n = 97) (HR 0.77, 95% CI 0.48–1.26, P = 0.3). Conclusion D2 resection followed by adjuvant chemotherapy provides similar long-term outcomes as compared to perioperative chemotherapy approach for stage IB/II/III distal GCs.

International audience; Background: In the phase III CheckMate 743 study (NCT02899299), first-line nivolumab plus ipilimumab significantly improved overall survival (OS) versus chemotherapy in patients with unresectable malignant pleural mesothelioma (MPM). We report updated data with 3-year minimum follow-up. Patients and methods: Adults with previously untreated, histologically confirmed, unresectable MPM and Eastern Cooperative Oncology Group performance status of = 3 years after discontinuation. Conclusions: With 3 years' minimum follow-up, nivolumab plus ipilimumab continued to provide long-term survival benefit over chemotherapy and a manageable safety profile, supporting the regimen as standard-of-care treatment for unresectable MPM, regardless of histology.

As a result of improved implants total ankle replacement (TAR) is becoming a more reliable option for end stage ankle arthritis. As with any surgery there are numerous complications that can occur intraoperatively and postoperatively with TAR. The primary aim of this study is to use recent data on implants currently on the market to develop a well-defined and comprehensive complication classification system which stratifies risk of subsequent surgery for TAR. A systematic review of studies on TARs from 2013 to 2018 was performed. Inclusion criteria were studies published between 2013 and August 2018, studies having at least 20 patients, data with at least 1-year follow-up and use of implants currently on the market. Studies were excluded if they involved revision cases, case reports, basic science articles and studies published in non-peer-reviewed journals. Sixteen studies fit inclusion criteria involving 3,305 implants. Overall survival of all implants was found to be 93% with a pooled complication rate of 75.6% using criteria for classifying complications by Glazebrook et al. Previously published classification systems did not clearly define complication categories leading to inconsistency in complication reporting and inaccurate complication rates. There are also several complications that are unclassifiable with the classifications developed by Gadd et al and Glazebrook et al. Our proposed updated classification system provides more inclusive tier profiles to capture the complications that can occur with implants currently on the market. Furthermore, this system provides a stratification of risk that these complications pose to ultimate procedure success.

Describe graft and overall survival outcomes in multiple myeloma (MM) patients who underwent kidney transplant (KT) compared to the general KT population.The Organ Procurement and Transplantation Network/National United Network for Organ Sharing (OPTON/UNOS) database was analyzed from 1988 to 2019 with R 4.00 and the 2013-2017 United States Renal Data System (USRDS) was surveyed for incidence and mortality of MM ESRD.USRDS analysis revealed 961 patients diagnosed with ESRD due to MM on average annually, accounting for 0.8% of the ESRD population. Without KT, 44.4% of MM patients died in the first year of renal replacement initiation. OPTON/UNOS analysis identified 218 MM KT patients, compared to 490,089 patients without MM. There was no difference in graft survival between MM KT and the general population (P-value = .13, HR = 1.19 [0.95, 1.49], 95% CI). Median graft survival in MM KT was 2683 days (7.4 years). KT patients with MM had a higher risk for death (P-value = .0001, HR = 1.83 [1.41, 2.37], 95% CI), and median overall survival was 3076 days (8.4 years). Survival difference was lost when comparing patients ≥50 years (P-value = .42, HR = 1.14 [0.83, 1.56], 95% CI).Patients with MM renal failure who underwent KT had equivalent graft and age-matched overall survival compared to the general KT population. Therefore select patients with MM renal failure have potential for excellent KT outcomes, should be considered for transplantation when feasible, and should not be excluded from KT based on a history of MM.

Most patients with pancreatic adenocarcinoma (PDAC) do not undergo surgical resection. The role of radiotherapy (RT) in non-operatively managed localized pancreatic adenocarcinoma is unclear.The National Cancer Database (2010-2016) was queried for patients with clinical stage II-III PDAC treated with multiagent systemic chemotherapy (CT) +/- RT but not surgery. Factors associated with the receipt of RT and overall survival were compared after adjusting for patient demographics and clinical characteristics.A total of 14,921 patients were included, of whom 9279 received CT and 5382 received CT + RT. Patients treated with CT + RT were more likely to be younger (65vs66yrs), treated at non-academic facilities (48.8%vs46.7%), have private insurance (40.3%vs36.5%), and have clinical T4 tumors (53.6%vs48.7%). Most patients who were treated with RT received external beam radiotherapy (89.3%), and the median dose was 5,000 cGy. Median time to start of RT was 129 days. CT + RT was associated with longer overall survival (15.9vs11.8mos,p 0.001), and remained associated with survival on multivariable analysis (HR 0.74, 95%CI 0.70-0.78). On a 4-month conditional survival analysis, combined CT + RT remained associated with improved survival compared to CT alone (16.0vs13.1mos,p 0.001).In patients with non-operatively managed localized pancreatic adenocarcinoma, combined radiotherapy and multiagent systemic chemotherapy is associated with improved overall survival compared to chemotherapy alone.

Background: Colorectal cancer is the fourth most diagnosed malignancy worldwide and surgery is one of the cornerstones of the treatment strategy. Near-infrared (NIR) fluorescence imaging is a new and upcoming technique, which uses an NIR fluorescent agent combined with a specialised camera that can detect light in the NIR range. It aims for more precise surgery with improved oncological outcomes and a reduction in complications by improving discrimination between different structures.Methods: A systematic search was conducted in the Embase, Medline and Cochrane databases with search terms corresponding to 'fluorescence-guided surgery', 'colorectal surgery', and 'colorectal cancer' to identify all relevant trials.Results: The following clinical applications of fluorescence guided surgery for colorectal cancer were identified and discussed: (1) tumour imaging, (2) sentinel lymph node imaging, (3) imaging of distant metastases, (4) imaging of vital structures, (5) imaging of perfusion. Both experimental and FDA/EMA approved fluorescent agents are debated. Furthermore, promising future modalities are discussed.Conclusion: Fluorescence-guided surgery for colorectal cancer is a rapidly evolving field. The first studies show additional value of this technique regarding change in surgical management. Future trials should focus on patient related outcomes such as complication rates, disease free survival, and overall survival. (C) 2021 The Authors. Published by Elsevier Ltd.

Statement of problem Implant-supported and implant-retained extraoral prostheses are reliable treatment options for patients with craniofacial defects. They provide stable retention and therefore enhance the patient's appearance and quality of life. Despite studies on survival rates of extraoral implants, little attention has been paid to the design of the implants used to support and retain extraoral prostheses. Purpose The purpose of this longitudinal clinical study was to assess the long-term survival rate (1 to 12 years, mean 6 years) of 2 different designs of implants (disk: single, double, and triple and screw-type) used for extraoral epithesis anchorage. Material and methods Twenty-six participants with orbital and nasal defects, 10 of whom had had radiation treatment, were included in the study. Disk implants and extraoral (EO) screw implants were used and placed in the periorbital (15 participants) and perinasal regions (11 participants). Data were analyzed by using the Chi-square test and the Fisher Exact test for qualitative variables and the Mann-Whitney U test for comparison of quantitative variables. Implant survival rates were calculated by Kaplan-Meier analysis. Results The overall 12-year survival rate of all implants was 90.3% (mean=79 months), with 92.9% for nasal (mean=84 months) and 88.2% for orbital (mean=75 months) implants. Related to the implant design, survival rates were as follows: for single-disk implants, 90.2%; for double disks, 94.6%; for triple disks, 88.3%; and for screw implants, 83.3%. In nonradiated participants, the implant survival rate was 97.6%, and for radiated participants, 76.1%. Conclusions Survival rates for implant-retained craniofacial prostheses are limited. The nasal site seems to be a more predictable implant site than the orbital site, with a higher overall survival rate. Also, implants inserted in radiated tissues have lower survival rates for both anatomic sites, with statistically significantly lower results in the orbital region. The most reliable type of implant among the disk implants used was the double disk in the orbital site and the single disk in the nasal site, which may indicate the advantages of some designs in specific areas.

OBJECTIVE: In the present study, we used a validated socioeconomic status (SES) index and population-based registry to identify and quantify the impact of SES on access to treatment and overall survival for patients diagnosed with synchronous brain metastases. METHODS: The Surveillance, Epidemiology, and End Results database was used to extract all patients between 2010 and 2016 with brain metastases at initial presentation. SES was stratified into tertiles and quintiles using the validated Yost index. Multivariable logistic regressions were used to evaluate the impact of demographic, tumor, and socioeconomic covariates on receipt of radiotherapy and chemotherapy. Kaplan-Meier curves were used to estimate survival. RESULTS: Between 2010 and 2016, 35,595 patients presented with brain metastases at the time of primary cancer diagnosis. Most patients received radiation and/or chemotherapy as part of the initial course of their treatment; 71.6% (n = 25,484) were irradiated while 54.4% (n = 19,371) received chemotherapy and 44.9% (n = 15,984) received chemoradiation. Patients in the highest Yost tertile and quintile experienced longer overall survival (P < 0.001). Additionally, multivariable logistic regression revealed that the lowest Yost quintile was significantly less likely to receive either radiation (adjusted OR: 0.82; 95% confidence interval: 0.75–0.89; P < 0.001) or chemotherapy (adjusted OR: 0.62; 95% confidence interval: 0.58–0.67; P < 0.001). CONCLUSIONS: In a large, population-based analysis of brain metastasis patients, we found significant differences in treatment access and mild survival differences along socioeconomic strata. More specifically, patients in lower SES tiers suffered worse outcomes and received radiation and chemotherapy less frequently than patients in higher tiers, even after accounting for other tumor- and demographic-related information.

INTRODUCTION: This double-blind, parallel-group, active-controlled phase III trial (NCT02260804) assessed CT-P10 and rituximab safety and efficacy in patients with previously untreated low-tumor-burden follicular lymphoma (LTBFL), including after a single switch from rituximab to CT-P10. PATIENTS AND METHODS: LTBFL patients were randomized (1:1) to receive CT-P10 or rituximab (375 mg/m(2) intravenously; day 1 of 4 7-day cycles). Patients achieving disease control entered a 2-year maintenance period. CT-P10 or rituximab were administered every 8 weeks (6 cycles) in year 1; all patients could receive CT-P10 (every 8 weeks; 6 cycles) in year 2. Secondary endpoints (reported here) were overall response rate (ORR) during the study period, progression-free survival (PFS), time to progression (TTP), and overall survival (OS). Safety and immunogenicity were evaluated. RESULTS: Between November 9, 2015 and January 4, 2018, 258 patients were randomized (130 for CT-P10; 128 for rituximab). ORR was similar between groups over the study period (CT-P10: 88%; rituximab: 87%). After 29.2 months' median follow-up, median PFS, TTP, and OS were not estimable; 24-month Kaplan-Meier estimates suggested similarity between groups. Overall, 114 (CT-P10: 88%), and 104 (rituximab: 81%) patients experienced treatment-emergent adverse events. The single switch was well tolerated. CONCLUSION: These updated data support therapeutic similarity of CT-P10 and rituximab and support the use of CT-P10 monotherapy for previously untreated LTBFL.

Background miRNAs play crucial roles in cancers. This study investigated the potential value of miR-875 to be a detective or/and prognostic marker and evaluate the correlation between its expression and PHH3 index levels in breast cancer. Methods miR-875 expression was determined in breast cancer serum and tissues by a quantitative real-time reverse transcription-polymerase chain reaction. The detective value of serum miR-875 expression for breast cancer was assessed by receiver operating characteristic analysis. Then the associations of miR-875 expression with clinical characteristics of patients and overall survival were evaluated by χ2 test and Kaplan-Meier curve methods, respectively. Results The expression of miR-875 was increased in both breast cancer serum and tissues compared with respective controls. The high miR-875 expression in serum and tissues was associated with positive lymph node metastasis and advanced TNM stages. Besides, miR-875 expression in tissues was positively associated with the PHH3 index. And serum miR-875 could screen breast cancer patients from healthy individuals. Moreover, breast cancer patients with both high expression of miR-875 and PHH3 index had shorter overall survival. Conclusion This study suggested that miR-875 expression may be suitable as a potential breast cancer detection and prognosis biomarker. And the miR-875 expression in tissues was positively associated with the PHH3 index, suggesting that miR-875 expression may be involved in tumor proliferation of breast cancer.

Objective : To provide an overview of the literature on the mid-term outcomes of chimney EVAR (ChEVAR) for the treatment of juxtarenal abdominal aortic aneurysms (JAAA). Methods : Different electronic databases were searched for published articles up to January 2020. The eligibility criteria were studies describing mid- or long-term outcomes of chimney EVAR (mean follow-up at least 1 year) for treatment of JAAA, including more than 10 cases, published in English, and with full text available. The outcomes measure were overall survival rate, target vessel patency, and freedom from reintervention at 3 years. Quality of the included studies was analysed using the MINORS criteria. Pooled effect estimates were analysed using random-effect models and heterogeneity was tested using I2 statistics. Results : Thirteen articles met the inclusion criteria. The included studies described 1,019 patients. According to the quality assessment, methodological quality was moderate to poor. The pooled overall survival, freedom from reintervention, and target vessel patency at 3 year was 81.4 % (95%CI 73.8 to 87.9), 85.7% (95%CI 75.6 to 93.5), and 95.1% (95%CI 89.3 to 98.7) respectively. Conclusion : The results of this review show good to acceptable short and mid-term survival and good mid-term durability, which supports that ChEVAR as a suitable alternative in high-risk JAAA. However, proper patient selection for ChEVAR seems essential to attain good mid-term outcomes, and further large prospective and good quality studies are required to demonstrate its long-term results and enable conclusions on specific determinants for outcome.

Aim Drug approvals for genome-informed indications have been increasing in recent years, but it is unknown how many of them have demonstrated an improvement in overall survival (OS). We assessed the frequency of approved genome-informed drugs demonstrating improvements in OS and progression-free survival (PFS) and whether the frequencies differed by cancer type. Materials and methods We searched all Food and Drug Administration approvals from 2006 to 2020, and for each drug that was approved for a genomic indication, we then searched on PubMed for randomised studies examining OS or PFS. Results We found 53 drugs approved for 92 unique indications from 2006 to 2020. We found that 50 drugs (55%) approved for a genomic indication had a randomised study evaluating OS benefit, and of those, only 22 demonstrated an improvement in OS. Similarly, 52 drugs (57%) evaluated PFS benefit, and 51 of these studies demonstrated an improvement in PFS. Drugs approved for BRAF V600 melanoma demonstrated an improvement in OS more often than drugs approved for ALK non–small cell lung cancer. The median improvement in OS was 4.7 months (range 1.5 months–49.1 months). Conclusion Although there is widespread enthusiasm for this class of agents, and many demonstrate impressive response rates, further trials or post-marketing studies are needed to ascertain the impact on survival and quality of life, the magnitude of these gains, and the cost-effectiveness of these agents.

BACKGROUND: We sought to identify characteristics of metastatic breast cancer (MBC) patients who may benefit most from primary tumor resection. METHODS: Recursive partitioning analysis (RPA) was used to categorize non-surgical patients with de novo MBC in the NCDB (2010–2015) into 3 groups (I/II/III) based on 3-year overall survival (OS). After bootstrapping (BS), group-level profiles were applied, and the association of surgery with OS was estimated using Cox proportional hazards models. RESULTS: All patients benefitted from surgery (median OS, surgery vs no surgery): 72.7 vs 42.9 months, 47.3 vs 30.4 months, 23.8 vs 14.4 months (all p

Introduction Surgery plays a key role in the management of Neuroblastic tumours (NB), where the standard approach is open surgery, while minimally invasive surgery (MIS) may be considered an option in selected cases. The indication(s) and morbidity of MIS remain undetermined due to small number of reported studies. The aim of this study was to critically address the contemporary indications, morbidity and overall survival (OS) and propose guidelines exploring the utility of MIS for NB. Materials & Methods: A SIOPEN study where data of patients with NB who underwent MIS between 2005 and 2018, including demographics, tumour features, imaging, complications, follow up and survival, were extracted and then analysed. Results A total of 222 patients from 16 centres were identified. The majority were adrenal gland origin (54%) compared to abdominal non-adrenal and pelvic (16%) and thoracic (30%). Complete and near complete macroscopic resection (>95%) was achieved in 95%, with 10% of cases having conversion to open surgery. Complications were reported in 10% within 30 days of surgery. The presence of IDRF (30%) and/or tumour volume >75 ml were risk factors for conversion and complications in multivariate analysis. Overall mortality was 8.5%. Conclusions MIS for NB showed that it is a secure approach allowing more than 95% resection. The presence of IDRFs was not an absolute contraindication for MIS. Conversion to open surgery and overall complication rates were low, however they become significant if tumour volume >75 mL. Based on these data, we propose new MIS guidelines for neuroblastic tumours.

International audience; BackgroundAllogeneic hematopoietic stem-cell transplantation (allo-HSCT) remains the best curative option for high-risk myelodysplastic syndrome . We retrospectively compared patient outcomes after allo-HSCT according to the intensity of the conditioning regimen.Patients and MethodsThree conditioning regimens were compared in 427 patients allografted for high-risk myelodysplastic syndrome: reduced-intensity conditioning (RIC), fludarabine (150-160 mg/m2) and busulfan (6.4 mg/kg); sequential FLAMSA-RIC, fludarabine, amsacrine, and aracytine followed by RIC; and myeloablative with reduced toxicity (RTC), fludarabine and busulfan (9.6 mg/kg or 12.8 mg/kg).ResultsThe patients in the 3 conditioning groups were different in regards to the number of treatment lines (P< .001), percentage of blasts in bone marrow (P< .001), and disease status at transplantation (P< .001). No significant differences in outcomes (overall survival, progression-free survival, nonrelapse mortality, relapse incidence, and graft versus host disease relapse-free survival) were observed between the 3 groups. Using propensity score analysis to overcome baseline imbalances, we compared 70 patients receiving FLAMSA-RIC to 260 patients receiving RIC, and compared 83 patients receiving RTC to 252 patients receiving RIC. The only factor influencing overall and progression-free survival was cytogenetic risk at transplantation. After the covariate adjustment using propensity score to reduce baseline imbalances, the only factor influencing overall and progression-free survival was still cytogenetic risk at transplantation.ConclusionOverall survival appears to be similar with the 3 conditioning regimens. The only factor influencing survival is cytogenetic risk at transplantation, suggesting that new promising drugs in the conditioning and/or early interventions after transplantation are needed to improve outcomes in these patients.

Eribulin is a tubulin and microtubule-targeting drug that has clinical benefit in overall survival (OS) for patients with advanced soft tissue sarcoma. Eribulin's efficacy has been confirmed in several clinical trials, although no clinically useful biomarkers have been identified. We therefore sought to clarify the predictive factor of eribulin treatment, while focusing on systemic inflammation and immune response values.This study included 33 advanced STS patients treated with eribulin between March 2016 and September 2019. We evaluated the associations of clinical factors influencing the efficacy of eribulin treatment and systemic inflammatory and immune response, including the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the lymphocyte-to-monocyte ratio (LMR), the systemic inflammation response index (SIRI), and the prognostic nutrition index (PNI), with progression-free survival (PFS) and OS using the Kaplan-Meier method and log-rank test.NLR, LMR, PLR, SIRI, and PNI were unassociated with PFS. Compared with patients with SIRI1.5, those with an SIRI ≥1.5 had a significantly shorter OS [median OS 15 months (95% confidence interval [CI] 8-not reached) vs. 7 months (95% CI 3-14), P = 0.04]. Moreover, the PFS tended to be shorter for patients with SIRI ≥1.5 who received chemotherapy after eribulin treatment than in those with SIRI1.5 [median PFS 92.5 days (95% CI 27-204) vs. 133 days (95% CI 36-507), P = 0.08].High SIRI values may predict poorer overall survival and the efficacy of subsequent drugs after eribulin treatment among patients with advanced soft tissue sarcoma.

Objectives To compare perioperative and oncologic outcomes of intracorporeal (ICNB) and extracorporeal neobladder (ECNB) following robot assisted radical cystectomy (RARC) from a multi-institutional, prospectively maintained database, the International Robotic Cystectomy Consortium (IRCC). Methods A retrospective review of IRCC database between 2003 and 2020 (3742 patients from 33 institutions across 14 countries) was performed (I-97906). The Cochran-Armitage trend test was used to assess utilization of ICNB over time. Multivariate logistic regression models were fit to evaluate variables associated with receiving ICNB, overall complications, high-grade complications, and readmissions after RARC. Kaplan Meier curves were used to depict recurrence-free (RFS), disease-specific (DSS), and overall survival (OS). Results 411 patients received neobladder, 64% underwent ICNB. ICNB utilization increased significantly over time (p Conclusion Utilization of ICNB increased significantly over time. Patients who underwent RARC and ICNB had shorter hospital stays and fewer 30-d reoperations but were readmitted more frequently compared to those who underwent ECNB.

Tall cell and diffuse sclerosing variants of papillary thyroid cancer are associated with aggressive features. Radioactive iodine after total thyroidectomy is poorly studied.Patients ≥18 years in the National Cancer Data Base from 2004 to 2016 with classic papillary thyroid cancer, tall cell, or diffuse sclerosing 1 mm to 40 mm were identified. Logistic regression identified factors associated with aggressive features. Overall survival was assessed using Kaplan-Meier method and log-rank tests, after propensity score matching for clinicopathological and treatment variables.A total of 155,940 classic papillary thyroid cancer patients, 4,011 tall cell, and 507 diffuse sclerosing were identified. Tall cell patients represented an increasing proportion of the study population during the analysis period, whereas diffuse sclerosing and classic papillary thyroid cancer patients showed a statistically significant decline. Extrathyroidal extension and nodal involvement were more prevalent among tall cell and diffuse sclerosing patients when compared to those diagnosed with classic papillary thyroid cancer (P.01). Adjuvant radioactive iodine was less frequently used in patients with classic papillary thyroid cancer when compared to tall cell and diffuse sclerosing patients (42.6% vs 62.4%, 59.0%; P.001, respectively). Aggressive variants receiving total thyroidectomy versus total thyroidectomy + radioactive iodine propensity score matched across clinicopathologic variables were analyzed. There was no difference in overall survival between the 2 treatment groups for tumors2 cm (01-1.0 cm, 92.2% vs 84.8%; P = .98); (1.0-2.0 cm, 72.7% vs 88.1%; P = .82). However, overall survival was improved for total thyroidectomy + radioactive iodine propensity score matched patients with tumor sizes 21 to 40 mm versus total thyroidectomy (83.4% vs 70.0%, P = .004).For aggressive tumor variants ≤2 cm treated with total thyroidectomy, there is no overall survival advantage provided by the addition of adjuvant radioactive iodine.

Take Home Message Increasing age, pre- and postoperative hydronephrosis, impaired baseline kidney function, and adjuvant chemotherapy contribute to significant kidney function decline following radical cystectomy. Nearly one-third of patients develop advanced chronic kidney disease within a year of radical cystectomy., Background Patients with chronic kidney disease (CKD) are poor candidates for standard treatments for muscle-invasive bladder cancer (MIBC) and may be more likely to experience adverse outcomes when diagnosed with MIBC. Objective To investigate factors associated with the development of advanced CKD following radical cystectomy. Design, setting, and participants Using national Veterans Health Administration utilization files, we identified 3360 patients who underwent radical cystectomy for MIBC between 2004 and 2018. Outcome measurements and statistical analysis We examined factors associated with the development of advanced CKD (estimated glomerular filtration rate [eGFR] of

Background To investigate outcomes of salvage whole-brain radiotherapy (WBRT) for recurrent brain metastases (BM) from breast cancer (BC), to identify prognostic factors of overall survival (OS), and to propose a novel prognostic classification for OS in these patients. Materials and methods We identified 54 patients who had received salvage WBRT as the second brain-focused treatment for recurrent BM from BC (2000–2014). The median follow-up duration was 4.9 months. A recursive partitioning analysis (RPA) was conducted to develop a model to predict OS at the time of salvage WBRT. Results The median OS was 6.8 months. OS according to BC-specific graded prognostic assessment (breast-GPA), modified breast-GPA, and updated breast-GPA did not represent our cohort. In the multivariate analysis, a long time before salvage WBRT (≥16 months), control of primary BC or extracranial metastases, systemic treatment after salvage WBRT, and administration of a biologically effective dose for an α/β of 10 Gy (BED10) of salvage WBRT >37.5 Gy showed superior OS. We proposed three RPA classes based on the control of both primary BC and extracranial metastasis and BED10 of salvage WBRT: class I, class II, and class III. In this model, patients with class I experienced the best OS (34.6 months; class II, 5.0 months; class III, 2.4 months; P, Highlights • Multicenter retrospective study of salvage WBRT for recurrent brain metastasis. • Subsequent use of systemic treatment after salvage WBRT showing better OS. • Limitations of previous graded prognostic assessments for recurrent brain metastasis. • Novel RPA classification consisting of four simple clinical factors predicts OS.

Background Real-world evidence suggest that next generation hormonal agents (NHAs) abiraterone and enzalutamide were preferred as first-line (1L) therapies for metastatic castration-resistant prostate cancer (mCRPC) in the United States (US) pre-2020, with chemotherapies, particularly docetaxel, being preferred in subsequent lines (2L+). This real-world study described patient characteristics, treatment patterns, time on treatment (ToT) and overall survival (OS) among patients with mCRPC treated with 2L and 3L docetaxel post-NHAs in the mCRPC setting. Methods Adults with confirmed adenocarcinoma mCRPC diagnosis and ≥1 month of follow-up post-diagnosis were selected from a US electronic health record-derived oncology de-identified database (01/2013–03/2019). Based on the observed line of therapy sequences post-mCRPC diagnosis, patients who received NHA therapy in 1L and docetaxel therapy in 2L were included in the 2L docetaxel cohort, and patients who received NHA therapy in both 1L and 2L and docetaxel therapy in 3L were included in the 3L docetaxel cohort. ToT and OS were evaluated using Kaplan-Meier analysis. Results Among 5,213 patients with mCRPC, 278 and 166 were included in the 2L and the 3L docetaxel cohorts, respectively (median age: 73 years for both cohorts). ADT was the most used class of medication pre-mCRPC (>75%). For the 2L cohort, the most common sequence post-mCRPC was 1L abiraterone → 2L docetaxel (52.5%), while the median ToT and OS post-2L start were 4.1 and 10.5 months, respectively; for the 3L cohort, the most common sequence post-mCRPC was 1L abiraterone → 2L enzalutamide → 3L docetaxel (67.5%), while the median ToT and OS post-3L start were 3.8 and 8.7 months, respectively. Conclusions This real-world study provides novel data on patients treated with docetaxel post-NHAs in a mCRPC setting and highlights the critical unmet need for developing more effective treatment options in this population.

Circular (circ)RNAs are widely involved in gastric cancer (GC) pathogenesis, and coiled-coil domain containing 6 (CCDC6) is a fused partner of multiple oncogenes; however, the underlying mechanisms of how circRNAs regulate CCDC6 expression in the progression and prognosis of GC remain unclear. Here, we discovered the circRNA derived from the DNA2 gene locus (circDNA2) through RNA sequencing. By performing quantitative real-time PCR and fluorescence in situ hybridization (FISH) assays with a human tissue microarray, circDNA2 was found to be highly expressed in GC tissues and associated with lymphatic invasion of GC patients. Knockdown of circDNA2 expression suppressed the proliferation of GC cells by reducing CCDC6 expression. Mechanistically, circDNA2 acted as a microRNA (miR)-149-5p sponge, which was confirmed to target CCDC6 by RNA pulldown and dual-luciferase reporter assays and rescue experiments. Both low miR-149-5p expression and high CCDC6 expression were related to unfavorable prognosis in GC patients. Moreover, GC patients with low miR-149-5p expression had shorter overall survival and a higher risk of chemotherapy resistance than those with high miR-149-5p expression. In summary, circDNA2 contributes to the growth and lymphatic metastasis of GC by upregulating CCDC6 expression by sponging miR-149-5p. The circDNA2/miR-149-5p/CCDC6 axis might be developed as a therapeutic target and prognostic indicator for GC., Graphical abstract, Jin et al. revealed that circDNA2 contributes to the growth and lymphatic metastasis of GC by upregulating CCDC6 expression by sponging miR-149-5p. The circDNA2/miR-149-5p/CCDC6 axis might be developed as a therapeutic target and prognostic indicator for GC patients.

Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine malignancy of the skin. Its incidence is increasing with half of cases involving the head and neck. To the best of our knowledge, few large studies have been published in the UK, and to date this is the largest reported series of head and neck MCC. We retrospectively reviewed the outcomes of patients with MCC in three hospitals in the south-east of England over a 12-year period (2008–2019). Diagnosis was based on histological data following biopsy. Overall survival and disease-specific survival were calculated using Kaplan–Meier and log-rank tests. Fifty-eight patients met the inclusion criteria (24 stage I, 22 stage II, 9 stage III, and 3 unclassified). Median disease-free survival was 36 months (95% CI 0 to 77.2) and median overall survival 50 months (95% CI 29.9 to 70). Overall five-year survival was 34.4% (95% CI 17% to 52%) with two-year survival at 62% (95% CI 48% to 76%). Five-year disease-free survival was 26.7% (95% CI 17 to 52%) with two-year disease-free survival at 54% (95% CI 40% to 68%). To date, this is the largest UK based study reporting overall and disease-free survival associated with MCC of the head and neck. Half the patients presented late, and surgery was the mainstay of treatment, augmented by adjuvant radiotherapy. There is a need to better stratify patients at risk of developing metastatic disease, with the use of sentinel lymph node biopsy and positron-emission tomography-computed tomography (PET-CT), as immunotherapy and targeted agents are now available to treat advanced disease.

BACKGROUND: More than half of patients treated with esophagectomy for esophageal cancer experience recurrence. Oligometastasis, a proposed intermediate state of isolated local or solid-organ recurrence that occurs before widespread systemic disease, is a potential target for aggressive local intervention. We investigated presentation and prognosis between solid-organ recurrence sites. METHODS: Patients with isolated solid-organ recurrence at the liver, lung, or brain who underwent R0 esophagectomy from 1995 to 2016 were identified. Clinicopathologic characteristics and outcomes were compared between sites of recurrence. Overall survival was quantified using the Kaplan-Meier approach and Cox proportional hazards models. RESULTS: In total, 104 patients were included (site: brain, 37; lung, 27; liver, 40). Eighty percent of liver, 51% of brain, and 44% of lung oligometastases occurred in the first 12 months after esophagectomy. Despite the limited use of aggressive therapy, patients with lung oligometastasis had significantly longer median overall survival (2.41 years; 95% confidence interval [CI], 1.58–3.31) than patients with brain (0.95 years; 95% CI, 0.62–1.49) or liver (0.95 years; 95% CI, 0.82–1.41) oligometastasis (p

Background There is still uncertainty regarding the role of perioperative chemotherapy (CTx) in patients with resectable colorectal liver metastases (CRLM), especially in those with a low-risk of recurrence. Methods Multicentre retrospective analysis of patients with CRLM undergoing liver resection between 2010–2015. Patients were divided into two groups according to whether they received perioperative CTx or not and were compared using propensity score matching (PSM) analysis. Then, they were stratified according to prognostic risk scores, including: Clinical Risk Score (CRS), Tumour Burden Score (TBS) and Genetic And Morphological Evaluation (GAME) score. Results The study included 967 patients with a median follow-up of 68 months. After PSM analysis, patients with perioperative CTx presented prolonged overall survival (OS) in comparison with the surgery alone group (82.8 vs 52.5 months, p = 0.017). On multivariable analysis perioperative CTx was an independent predictor of increased OS (HR 0.705, 95%CI 0.705–0.516, p = 0.029). The benefits of perioperative CTx on survival were confirmed in patients with CRS and TBS scores ≤2 (p = 0.022 and p = 0.020, respectively) and in patients with a GAME score ≤1 (p = 0.006). Conclusion Perioperative CTx demonstrated an increase in OS in patients with CRLM. Patients with a low-risk of recurrence seem to benefit from systemic treatment.

Background Mutations in TP53 in myeloid neoplasms patients have been associated with poor prognosis. Effective treatments to these patients remain unclear. Patients and Methods In this study, we retrospectively analyzed diagnostic and outcomes of 31 Acute Myeloid leukemia (AML) and 9 Myelodysplastic syndromes (MDS) patients with TP53 mutation at our hospital from September 2015 to October 2020. Results A total of 42 variants (28 unique variants) in the coding region of TP53 gene were identified, and most were missense mutation (34 of 42, 81%). The median overall survival (OS) was 8 months for the AML patients (1-32 months) and 7 months for the MDS patients (3-27 months). There were 35 and 13 patients underwent frontline chemical therapy and Allo-HSCT, respectively. The overall response rate was 45.3% (16/35) for the frontline treatment. There was no significant difference between intensive and low-intensity regimens on either response to the frontline treatment (P = .255) or overall survival (P = .078). Patients, who achieved complete or partial remission at the frontline treatment, presented a higher survival than patients in non–remission, no matter transplant or not. Conclusion This study corroborates that improving the response to the first-line treatment could prolong the survival of myeloid neoplasms patients with TP53 mutation. Allo-HSCT could be a curative option for patients with TP53 mutation, when in complete remission during the first-line treatment.

Background Since 2006, surgery combined with perioperative chemotherapy is the standard of care for resectable gastric adenocarcinoma in Europe. Specific effects of neoadjuvant chemotherapy remain unknown. The aim was to evaluate the rate of tumor downstaging and its impact on survival in patients undergoing curative resection after neoadjuvant chemotherapy (NeoCT) for gastric adenocarcinoma. Material and Methods All patients treated in a curative intent for gastric or esophagogastric junction adenocarcinomas between 1996 and 2016 in our high-volume center were retrospectively included. Tumor downstaging after NeoCT was defined as ypTN inferior to cTN. The accuracy of clinical staging was evaluated in patients treated by upfront surgery before 2006. Results During the study period, 491 patients were operated for gastric adenocarcinoma, and 449 patients were finally analyzed. Among the 163 (36.3%) patients who received NeoCT, 61 (37.4%) had tumor downstaging. Overall survival and disease-free survival were longer in patients with tumor downstaging compared to patients without it (5-year survival: 84.8% vs 49.7%; P = .002 and 61.7% vs 43.4%; P = .054). In multivariate analysis tumor downstaging was an independent prognosis factor for better overall survival (HR = 5.258; P = .002) and disease-free survival (HR = 2.286; P = .028). Moreover, 45.5% of patients staged cT1-T2N0, in whom upfront surgery was performed, were understaged and ultimately had a more advanced tumor on pathological analysis. Conclusion Response to neoadjuvant chemotherapy constitutes a major prognostic factor for overall and disease-free survival. In the absence of predictive factors for tumor downstaging, the indication for perioperative chemotherapy should remain broad, in particular because of the low accuracy of pretherapeutic staging and therefore the high risk of understaging tumors.

To date, there is controversy regarding unilateral versus bilateral stent placement in patients with malignant hilar biliary strictures (MHBSs). The aim of this study was to compare the clinical outcomes and complications of unilateral and bilateral (stent-in-stent method) stent placements for these patients.We conducted a multicenter retrospective analysis of patients with inoperable MHBS who underwent endoscopic self-expandable metal stent (SEMS) placement from January 2009 to December 2019. Two groups classified according to the stent procedure method were compared for demographic, procedural, and postprocedure factors. Survival analysis for patency loss and overall survival was also conducted.A total of 236 subjects were included. A superior technical success rate was found in the unilateral stent group (98.8% vs. 82.5%, P0.001), whereas the clinical success rate was higher in the bilateral group (85.7% vs. 70.5%, P = 0.028). There was no significant difference with respect to complications or patency loss, and the bilateral group had better overall survival (P0.01). In the Cox proportional hazard model, MHBSs from lymph node compression were associated with a higher risk of death (HR = 9.803, P = 0.003). In contrast, bilateral SEMS insertion showed reduced postprocedural mortality (HR = 0.316, P = 0.001).Y-type stent-in-stent bilateral SEMSs are technically difficult but demonstrated more favorable overall survival for palliative bile drainage of inoperable MHBS patients compared to unilateral insertions.

BACKGROUND: For patients with non-small cell lung cancer (NSCLC) receiving immune checkpoint inhibitors, PD-L1 tumor proportion score has been validated as a predictive biomarker for improved overall survival. However, its histology-specific predictive value in patients with advanced squamous versus nonsquamous cancers remains unclear. PURPOSE: To assess the differential value of PD-L1 tumor proportion score (TPS) as a predictive biomarker for overall survival after first-line pembrolizumab in patients with squamous versus nonsquamous NSCLC. BASIC PROCEDURES: Retrospective, observational study of patients diagnosed with advanced NSCLC who were treated between October 2015 and April 2019 at community oncology clinics and academic medical centers in a de-identified EHR-derived database. Included patients were diagnosed with advanced or metastatic NSCLC, received treatment with first-line, single agent pembrolizumab, and had documentation of PD-L1 testing with a numeric result. Exclusion criteria included alterations in EGFR, ALK, and ROS1.The primary endpoint was overall survival from start of first-line pembrolizumab therapy by squamous or nonsquamous histology and PD-1 expression level measured by TPS (low

Summary Background The primary analysis of the phase 3 NETTER-1 trial showed significant improvement in progression-free survival with 177Lu-Dotatate plus long-acting octreotide versus high-dose long-acting octreotide alone in patients with advanced midgut neuroendocrine tumours. Here, we report the prespecified final analysis of overall survival and long-term safety results. Methods This open-label, randomised, phase 3 trial enrolled patients from 41 sites in eight countries across Europe and the USA. Patients were 18 years and older with locally advanced or metastatic, well differentiated, somatostatin receptor-positive midgut neuroendocrine tumours (Karnofsky performance status score ≥60) and disease progression on fixed-dose long-acting octreotide. Patients were randomly assigned (1:1) via an interactive web-based response system to intravenous 177Lu-Dotatate 7·4 GBq (200 mCi) every 8 weeks (four cycles) plus intramuscular long-acting octreotide 30 mg (177Lu-Dotatate group) or high-dose long-acting octreotide 60 mg every 4 weeks (control group). The primary endpoint of progression-free survival has been previously reported; here, we report the key secondary endpoint of overall survival in the intention-to-treat population. Final overall survival analysis was prespecified to occur either after 158 deaths or 5 years after the last patient was randomised, whichever occurred first. During long-term follow-up, adverse events of special interest were reported in the 177Lu-Dotatate group only. This trial is registered with ClinicalTrials.gov , NCT01578239 . Findings From Sept 6, 2012, to Jan 14, 2016, 231 patients were enrolled and randomly assigned for treatment. The prespecified final analysis occurred 5 years after the last patient was randomly assigned (when 142 deaths had occurred); median follow-up was 76·3 months (range 0·4–95·0) in the 177Lu-Dotatate group and 76·5 months (0·1–92·3) in the control group. The secondary endpoint of overall survival was not met: median overall survival was 48·0 months (95% CI 37·4–55·2) in the 177Lu-Dotatate group and 36·3 months (25·9–51·7) in the control group (HR 0·84 [95% CI 0·60–1·17]; two-sided p=0·30). During long-term follow-up, treatment-related serious adverse events of grade 3 or worse were recorded in three (3%) of 111 patients in the 177Lu-Dotatate group, but no new treatment-related serious adverse events were reported after the safety analysis cutoff. Two (2%) of 111 patients given 177Lu-Dotatate developed myelodysplastic syndrome, one of whom died 33 months after randomisation (this person was the only the only reported 177Lu-Dotatate treatment-related death). No new cases of myelodysplastic syndrome or acute myeloid leukaemia were reported during long-term follow-up. Interpretation 177Lu-Dotatate treatment did not significantly improve median overall survival versus high-dose long-acting octreotide. Despite final overall survival not reaching statistical significance, the 11·7 month difference in median overall survival with 177Lu-Dotatate treatment versus high-dose long-acting octreotide alone might be considered clinically relevant. No new safety signals were reported during long-term follow-up. Funding Advanced Accelerator Applications, a Novartis company.

BACKGROUND Tumor response and lymph node involvement are the most important prognosticators in resected patients with esophageal adenocarcinoma after neoadjuvant chemoradiation (nCRT). We hypothesise that lymph node response (LNR) is also a valuable prognosticator in these patients, potentially revealing the added effect of nCRT. METHODS Hematoxylin-eosin slides of 193 esophageal adenocarcinoma patients with clinical suspicion of lymph node involvement (cN+) and treated with nCRT between 2008 and 2015 were assessed. Lymph nodes containing viable tumor cells were considered ypN+ and those negative for viable tumor were ypN0. LNR was also described according to an earlier defined method. Three groups were obtained: ypN0/LNR-, ypN0/LNR+ and ypN+. They were compared to 188 cN+ patients being pN0 (n=45) or pN+ (n=143) after upfront esophageal resection. RESULTS 44 patients were ypN0/LNR-, 55 ypN0/LNR+ and 94 ypN+. Median overall survival was respectively 96.4, 31.2 and 20.6 months and was significantly different between ypN0/LNR- and ypN0/LNR+ groups (p=0.020). Survival was comparable between ypN0/LNR- and pN0 (104.2 months) groups (p=0.519) and between ypN+ and pN+ (21,6 months) groups (p=0,966). In ypN0 patients, risk of death in LNR+ patients was tripled compared to LNR- patients. CONCLUSIONS In cN+ esophageal adenocarcinoma patients treated with nCRT with postoperative final pathology being ypN0, median overall survival is tripled when no signs of LNR were found and comparable to cN+/pN0 upfront esophagectomy patients, suggesting that 23% of patients treated with nCRT were in fact true N0 and overtreated by nCRT. ypN+ patients have no survival benefit compared to pN+ patients. ispartof: The Annals of Thoracic Surgery vol:112 issue:6 pages:1-28 ispartof: location:Netherlands status: Published online

Background Brentuximab-vedotin (BV) monotherapy has shown high efficacy in heavily pre-treated patients with relapsed or refractory Hodgkin lymphoma (HL) after high-dose chemotherapy or autologous stem cell transplantation (ASCT). We retrospectively analyzed the outcomes of treatment with BV of HL patients and examined the predictive ability of PET-CT for response in this setting. Patients and methods Records of 49 HL patients (median age, 39 years, 55% male) treated with BV for relapse (71.4%) or consolidation (28.6%) post-ASCT were analyzed. Patients who did not reach complete response (CR) on PET/CT after 4 cycles (non-responders) discontinued BV and received the next treatment line. Overall survival (OS) and progression-free survival (PFS) were compared between responders and non-responders. Results After a median follow-up of 19.1 months, all consolidation patients were alive and none progressed. Median OS in 23 relapsed patients that did not achieve CR after 4 cycles and continued to the next treatment was 55.0 months, while all those in CR (n = 24) were alive (P = .0120). No statistically significant differences in OS were observed between responders and non-responders with relapsed HL (P = .1072). Median PFS evaluated after 4 BV cycles was significantly longer in responders compared to non-responders (47.9 vs. 1.5 months, P Conclusions HL patients treated with BV for relapse or consolidation who achieved CR by PET-CT after 4 cycles showed improved PFS and OS compared to non-responders. Non-responders treated for relapsed HL who proceeded to the next treatment line demonstrated comparable OS to responders.

The coronavirus disease 2019 (COVID -19) pandemic caused by the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) has affected almost every country in the world, resulting in severe morbidity, mortality and economic hardship, and altering the landscape of healthcare forever. Although primarily a pulmonary illness, it can affect multiple organ systems throughout the body, sometimes with devastating complications and long-term sequelae. As we move into the second year of this pandemic, a better understanding of the pathophysiology of the virus and the varied imaging findings of COVID-19 in the involved organs is crucial to better manage this complex multi-organ disease and to help improve overall survival. This manuscript provides a comprehensive overview of the pathophysiology of the virus along with a detailed and systematic imaging review of the extra-thoracic manifestation of COVID-19 with the exception of unique cardiothoracic features associated with multisystem inflammatory syndrome in children (MIS-C). In Part I, extra-thoracic manifestations of COVID-19 in the abdomen in adults and features of MIS-C will be reviewed. In Part II, manifestations of COVID-19 in the musculoskeletal, central nervous and vascular systems will be reviewed.

PURPOSE To confirm the prognostic value of radiologic extranodal extension (rENE) and its role in clinical-N classification in nasopharyngeal carcinoma (NPC) treated in a western institution. METHODS AND MATERIALS NPC treated between 2010 and 2017 were included. Pre-treatment MRI were reviewed for unequivocal rENE and its grade: grade-1: tumour invading through any nodal capsule but confined to perinodal fat; grade-2: ≥2 adjacent nodes forming a coalescent nodal mass; grade-3: tumour extending beyond perinodal fat to invade/encase adjacent structures. Overall survival (OS) and disease-free survival (DFS) were compared between rENE-positive (rENE+) and rENE-negative (rENE-) patients. Multivariable analysis (MVA) confirmed the prognostic importance of rENE and its grade. Staging schemas including rENE in N-classification were proposed and their performance evaluated. RESULTS A total of 274 patients were eligible (43 cN0; 231 cN-positive). rENE was identified in 83/231 (36%) cN-positive, including grade 1/2/3 rENE in 14/58/11 cases. Compared to rENE-, rENE+ patients had a lower OS (68% vs 89%, p