ResearchPad - Cancer Research https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Predicting the effect of 5‐fluorouracil–based adjuvant chemotherapy on colorectal cancer recurrence: A model using gene expression profiles]]> https://www.researchpad.co/product?articleinfo=N537c20d6-57d9-4f8d-98ba-7e2ac6cb51b0

ABSTRACT

It is critical to identify patients with stage II and III colorectal cancer (CRC) who will benefit from adjuvant chemotherapy (ACT) after curative surgery, while the only use of clinical factors is insufficient to predict this beneficial effect. In this study, we performed genetic algorithm (GA) to select ACT candidate genes, and built a predictive model of support vector machine (SVM) using gene expression profiles from the Gene Expression Omnibus database. The model contained four ACT candidate genes (EDEM1, MVD, SEMA5B, and WWP2) and TNM stage (stage II or III). After using Subpopulation Treatment Effect Pattern Plot to determine the optimal cutoff value of predictive scores, the validated patients from The Cancer Genome Atlas database can be divided into the predictive ACT‐benefit/‐futile groups. Patients in the predictive ACT‐benefit group with 5‐fluorouracil (5‐Fu)–based ACT had significantly longer relapse‐free survival (RFS) compared to those without ACT (P = .015); However, the difference in RFS in the predictive ACT‐futile group was insignificant (P = .596). The multivariable analysis found that the predictive groups were significantly associated with the effect of ACT (P interaction = .011). Consequently, we developed a predictive model based on the SVM and GA algorithm which was further validated to define patients who benefit from ACT on recurrence.

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<![CDATA[Mortality and admission to intensive care units after febrile neutropenia in patients with cancer]]> https://www.researchpad.co/product?articleinfo=N5789ae80-071e-4a33-9bf6-569e630ab0b1

Abstract

Febrile neutropenia (FN) is a critical complication of chemotherapy associated with increased in‐hospital mortality. However, associations with increased mortality and intensive care unit (ICU) admissions during longer follow‐up are not established. Patients treated with standard first‐line chemotherapy for solid cancers at Rigshospitalet, Denmark in 2010‐2016 were included. Incidence rate ratios (IRR) of all‐cause, infectious and cardiovascular mortality, and ICU admissions after FN were analyzed by Poisson regression. Risk factors at the time of FN were analyzed in the subpopulation of patients with FN; all‐cause mortality was further stratified by the time periods 0‐30, 31‐365, and 366+ days after FN. We included 9018 patients with gastric (14.4%) and breast (13.1%) cancer being the most common, 51.2% had locally advanced or disseminated disease and the patients had a median Charlson Comorbidity Index score of 0 (interquartile range, 0‐0). During follow‐up, 845 (9.4%) experienced FN and 4483 (49.7%) died during 18 775 person‐years of follow‐up. After adjustment, FN was associated with increased risk of all‐cause mortality, infectious mortality, and ICU admissions with IRRs of 1.39 (95% CI, 1.24‐1.56), 1.94 (95% CI, 1.43‐2.62), and 2.28 (95% CI, 1.60‐3.24). Among those with FN, having a positive blood culture and low lymphocytes were associated with excess risk of death and ICU admissions (predominantly the first 30 days after FN), while elevated C‐reactive protein and low hemoglobin predicted mortality the first year after FN. The risk of death varied according to the time since FN; adjusted IRR per additional risk factor present for the time periods 0‐30, 31‐365, and 366+ days after FN were 2.00 (95% CI, 1.45‐2.75), 1.36 (95% CI, 1.17‐1.57), and 1.17 (95% CI, 0.98‐1.41). FN was associated with increased mortality and risk of ICU admissions. An objectively identifiable subgroup of patients among those with FN carried this excess risk.

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<![CDATA[Combination of inflammatory score/liver function and AFP improves the diagnostic accuracy of HBV‐related hepatocellular carcinoma]]> https://www.researchpad.co/product?articleinfo=N8d57c885-e9e2-46d6-9270-e1981baaa4b6

Abstract

Background

Alpha‐fetoprotein (AFP), routinely used for diagnosis of hepatocellular carcinoma (HCC), is limited with relatively low sensitivity and high false positivity in HBV‐related HCC (HBV‐HCC). Thus, an alternative approach was explored to improve specificity/sensitivity for diagnosis of HBV‐HCC, using the combination of AFP, inflammatory score, and liver function.

Methods

Chronic hepatitis B (CHB) (n = 510) and HBV‐HCC (n = 473) patients were identified retrospectively for this study. The diagnostic value of single vs combined biomarkers for HBV‐HCC was analyzed, using ROC curve.

Results

It was observed that elderliness, male sex, cirrhosis, HBeAg+ or no‐antiviral therapy, and elevation of ALT, AST, neutrophil‐lymphocyte ratio (NLR), and AFP were associated with developing HBV‐HCC. However, the cut‐off ALT defined by Chinese standard, but not by AASLD, was a risk factor. Interestingly, AFP of HBeAg HBV‐HCC patients without cirrhosis was significantly higher than that of the HBeAg+ patients. AUC values for AFP, ALT, AST, or NLR were 0.84 (95% CI: 0.8150.862), 0.533 (95% CI: 0.5010.565), 0.696 (95% CI: 0.6660.725), or 0.684 (95% CI: 0.6540.713) with optimal cut‐off at 7.21 ng/mL, 43 IU/mL, 38 IU/mL, or 2.61, respectively. Combination of AFP with ALT, AST, and NLR improved the diagnostic performance for HBV‐HCC, compared to any of the single biomarkers or any other combinations among these patients (except no‐cirrhosis).

Conclusions

Elderliness, male sex, elevated ALT, AST, NLR, AFP, cirrhosis, HBeAg+, and no‐antiviral treatment were independent risk factors for HBV‐HCC. AASLD standard of ALT cut‐off value may not be suitable for the Chinese population. Regular monitoring of HCC among HBeAg patients with abnormal AFP may improve the management of HBV‐HCC. The diagnostic performance of AFP combined with ALT, AST, and NLR for HBV‐HCC was superior to single biomarker or any other combinations among these patients, and its diagnostic equation can be used as useful tool for differentiation of HBV‐HCC from CHB.

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<![CDATA[Patient reported symptoms associated with quality of life during chemo‐ or immunotherapy for bladder cancer patients with advanced disease]]> https://www.researchpad.co/product?articleinfo=Nf1431b6a-6996-4406-bc4a-7bbd3b479df8

Abstract

Background

Bladder cancer (BC) patients with advanced disease have poor outcomes. The use of patient‐reported outcomes (PROs) could lead to improvements in symptom management and hence quality of life (QoL). The aim of this study is to report correlations between selected PROs and QoL and thus to present symptoms that influence QoL. Identification of these symptoms during treatment can lead to earlier symptom management and thus secure improvements in QoL.

Methods

BC patients in chemo‐ or immunotherapy for locally advanced or metastatic disease reported weekly PROs for the duration of their treatment. The PROs included EORTC QLQ‐C30 and QLQ‐BLM30 and 45 selected PRO‐CTCAE items. Spearman's correlation analysis was performed for all PRO‐CTCAE items and QLQ‐C30 global QoL and subdomains.

Results

In this study, 78 BC patients reported 724 questionnaires. Spearman's analysis showed significant correlations between almost all PRO‐CTCAE items and the expected domain of QoL. The PRO‐CTCAE items with the strongest correlations with QoL were anxiety (F, frequency item) and emotional function (r s = −0.603, P < .0001), concentration (S, severity item) and cognitive function (r s = −0.704, P < .0001), discouraged (F) and emotional function (r s = −0.659, P < .0001), fatigue (S) and role function (r s = −0.659, P < .0001) and sad (F) and emotional function (r s = −0.711, P < .0001). The weakest correlations were found for the PRO‐CTCAE items urinary frequency, incontinence and urge, all with variations in the direction and significance of the correlations.

Conclusions

This study delivers information on which PROs may influence QoL for patients in clinical trials or daily clinic. Psychological issues have a strong impact on QoL and should be dealt with during treatment to secure the best possible QoL for BC patients.

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<![CDATA[Treatment optimization for recurrent hepatocellular carcinoma: Repeat hepatic resection versus radiofrequency ablation]]> https://www.researchpad.co/product?articleinfo=N7f2dace2-cba1-47e8-97cd-4e692ab627d5

Abstract

Background and aims

The optimal treatment strategy for recurrent hepatocellular carcinoma (HCC) remains unclear. Therefore, we aimed to compare the outcomes of repeat hepatic resection (RHR) and radiofrequency ablation (RFA) for recurrent HCC.

Method

From December 2004 to December 2015, 138 patients who underwent RHR and 194 patients who underwent RFA were enrolled. Propensity score matching (PSM) was performed to establish 1:1 RHR‐RFA group matching. Clinical outcomes were compared before and after matching.

Results

Before matching, the 1‐, 3‐, and 5‐year postrecurrence survival (PRS) rates were 91.8%, 82.0%, and 72.9% for the RHR group (n = 138) and 94.4%, 75.4%, and 61.7% for the RFA group (n = 194), respectively (P = .380). After matching, the PRS rates at 1, 3, and 5 years were 90.5%, 81.5%, and 71.8% for the RHR group (n = 120) and 91.0%, 61.0%, and 41.7% for the RFA group (n = 120), respectively (P = .002). In the subgroup analysis, the PRS rates for the RHR group were better than those for the RFA group for patients who relapsed within 2 years (P = .004) or patients with primary tumor burden beyond the Milan criteria (P = .004). Multivariate analysis showed that treatment allocation was identified as an independent prognostic factor for PRS.

Conclusion

Compared with RFA, RHR provided a survival advantage for recurrent HCC, especially for patients who relapsed within 2 years and those with primary tumor burden beyond the Milan criteria.

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<![CDATA[Significance of examined lymph nodes number and metastatic lymph nodes ratio in overall survival and adjuvant treatment decision in resected laryngeal carcinoma]]> https://www.researchpad.co/product?articleinfo=Nff84d6a8-edc7-4c87-b4f6-66c83a79c95d

Abstract

Objective

The value of adjuvant therapy in resected laryngeal cancer remains controversial. This large SEER‐based cohort study aimed to investigate the existing parameters of lymph node status that could predict survival outcomes and the prognostic value of adjuvant treatment in resected laryngeal carcinoma.

Methods

Population‐based data from the US Surveillance, Epidemiology, and End Results (SEER‐18) Program on patients after laryngectomy and lymphadenectomy (2004‐2015) were analyzed. The optimal cut‐off values for examined lymph nodes number (ELNs) and metastatic lymph nodes ratio (MLNR) were determined using the X‐tile program. Associations of ELNs and MLNR with overall survival were investigated through Cox regression analysis. A survival‐predicting model was then constructed to stratified patients. The prognostic value of adjuvant therapy was evaluated in different subgroups.

Results

A total of 2122 patients with resected laryngeal cancer were analyzed. A novel survival‐predicting model was proposed based on ELNs, MLNR, and other clinicopathological characteristics. Patients were stratified into three subgroups with the increasing risk of death. Only patients in the high‐risk group who receiving adjuvant treatment had a significantly better survival outcome than those receiving surgery alone.

Conclusion

A new survival‐predicting model was established in this study, which was superior in assessing the survival outcomes of patients with resected laryngeal cancer. Notably, this model was also able to assist in the decision making of adjuvant therapy for patients and physicians.

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<![CDATA[Once‐weekly (70 mg/m2) vs twice‐weekly (56 mg/m2) dosing of carfilzomib in patients with relapsed or refractory multiple myeloma: A post hoc analysis of the ENDEAVOR, A.R.R.O.W., and CHAMPION‐1 trials]]> https://www.researchpad.co/product?articleinfo=Nc60813d4-82b4-4e23-a408-398f8d0baa9b

Abstract

Combination of carfilzomib with dexamethasone (Kd) is approved for use in relapsed and/or refractory multiple myeloma (RRMM), with carfilzomib administered twice weekly at 56 mg/m2 (Kd56 BIW) or once weekly at 70 mg/m2 (Kd70 QW). Post hoc cross‐trial comparisons were performed to compare efficacy and safety profiles of Kd70 QW vs Kd56 BIW dosing schedules using data from three trials of patients with RRMM: A.R.R.O.W., CHAMPION‐1, and ENDEAVOR. To select for comparable patient populations, side‐by‐side efficacy and safety comparisons were performed in subgroups of patients with 2‐3 prior lines of therapy who were not refractory to bortezomib. The overall response rate (ORR) was 69.9% (95% confidence interval [CI], 61.7‐77.2) for Kd70 QW and 72.4% (95% CI, 65.9‐78.2) for Kd56 BIW. Median progression‐free survival (PFS) was 12.1 months (95% CI, 8.4‐14.3) for Kd70 QW and 14.5 months (95% CI, 10.2—not evaluable) for Kd56 BIW. Frequency of grade ≥ 3 adverse events (AEs) was 67.6% for Kd70 QW and 85.3% for Kd56 BIW. Regression analyses (adjusting for prognostic factors) of all patients in the trials who received Kd70 QW vs Kd56 BIW estimated a PFS hazard ratio of 0.91 (95% CI, 0.69‐1.19; P = .47) and an ORR odds ratio of 1.12 (95% CI, 0.74‐1.69; P = .61). These results suggest that Kd70 QW has a comparable efficacy profile compared with Kd56 BIW and represents a convenient and well‐tolerated treatment for patients with RRMM.

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<![CDATA[Next‐generation sequencing for BCR‐ABL1 kinase domain mutations in adult patients with Philadelphia chromosome‐positive acute lymphoblastic leukemia: A position paper]]> https://www.researchpad.co/product?articleinfo=N7fa47885-e8e9-4bcc-84f6-7986b54cbb4f

Abstract

Emergence of clones carrying point mutations in the BCR‐ABL1 kinase domain (KD) is a common mechanism of resistance to tyrosine kinase inhibitor (TKI)‐based therapies in Philadelphia chromosome‐positive (Ph+) acute lymphoblastic leukemia (ALL). Sanger sequencing (SS) is the most frequently used method for diagnostic BCR‐ABL1 KD mutation screening, but it has some limitations—it is poorly sensitive and cannot robustly identify compound mutations. Next‐generation sequencing (NGS) may overcome these problems. NSG is increasingly available and has the potential to become the method of choice for diagnostic BCR‐ABL1 KD mutation screening. A group discussion within an ad hoc constituted Panel of Experts has produced a series of consensus‐based statements on the potential value of NGS testing before and during first‐line TKI‐based treatment, in relapsed/refractory cases, before and after allo‐stem cell transplantation, and on how NGS results may impact on therapeutic decisions. A set of minimal technical and methodological requirements for the analysis and the reporting of results has also been defined. The proposals herein reported may be used to guide the practical use of NGS for BCR‐ABL1 KD mutation testing in Ph+ ALL.

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<![CDATA[Prognostic significance of the radiologic features of pneumonitis induced by anti‐PD‐1 therapy]]> https://www.researchpad.co/product?articleinfo=Nab469150-9724-4871-8488-f56e5117e4a5

Abstract

Background

Interstitial lung disease (ILD) induced by anti‐programmed‐cell death‐1 (PD‐1) and anti‐PD‐ligand 1 (PD‐L1) is potentially life‐threatening and is a common reason of the discontinuation of therapy. In contrast, an enhancement in antitumor effects was reported in patients who developed immune‐related adverse events, including ILD. Although recent evidence suggests that radiologic patterns of ILD may reflect the severity of ILD and the antitumor immune responses to anti‐PD‐1/PD‐L1 therapies, the association between radiologic features and clinical outcomes remains unclear.

Methods

Patients with advanced non‐small‐cell lung cancer who were treated with 1st to 3rd line anti‐PD‐1 therapy from January 2016 through October 2017 were identified at multiple institutions belonging to the Niigata Lung Cancer Treatment Group. ILD was diagnosed by the treating physicians, and chest computed tomography scans were independently reviewed to assess the radiologic features of ILD.

Results

A total of 231 patients who received anti‐PD‐1 therapy were enrolled. Thirty‐one patients (14%) developed ILD. Sixteen patients were classified as having ground glass opacities (GGO), 16 were classified as having cryptogenic organizing pneumonia (COP), and one was classified as having pneumonitis not otherwise specified. Patients with GGO had significantly worse overall survival time compared to patients with COP (7.8 months (95% CI: 2.2‐NE) versus not reached (95% CI: 13.2‐NE); P = 0.0175). Multivariate analysis of all 231 patients also revealed that PS = 1 and ≥2 and GGO were significant predictors of a worse overall survival.

Conclusions

This study demonstrated that patients who developed GGO exhibited worse outcomes among non‐small‐cell lung cancer patients receiving anti‐PD‐1 therapies.

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<![CDATA[Oncolytic virotherapy in hepato‐bilio‐pancreatic cancer: The key to breaking the log jam?]]> https://www.researchpad.co/product?articleinfo=Na6afd8d5-3cc4-4489-babe-7158830d6ad5

Abstract

Traditional therapies have limited efficacy in hepatocellular carcinoma, pancreatic cancer, and biliary tract cancer, especially for advanced and refractory cancers. Through a deeper understanding of antitumor immunity and the tumor microenvironment, novel immunotherapies are becoming available for cancer treatment. Oncolytic virus (OV) therapy is an emerging type of immunotherapy that has demonstrated effective antitumor efficacy in many preclinical studies and clinical studies. Thus, it may represent a potential feasible treatment for hard to treat gastrointestinal (GI) tumors. Here, we summarize the research progress of OV therapy for the treatment of hepato‐bilio‐pancreatic cancers. In general, most OV therapies exhibits potent, specific oncolysis both in cell lines in vitro and the animal models in vivo. Currently, several clinical trials have suggested that OV therapy may also be effective in patients with refractory hepato‐bilio‐pancreatic cancer. Multiple strategies such as introducing immunostimulatory genes, modifying virus capsid and combining various other therapeutic modalities have been shown enhanced specific oncolysis and synergistic anti‐cancer immune stimulation. Combining OV with other antitumor therapies may become a more effective strategy than using virus alone. Nevertheless, more studies are needed to better understand the mechanisms underlying the therapeutic effects of OV, and to design appropriate dosing and combination strategies.

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<![CDATA[Development and validation of a novel nomogram for pretreatment prediction of liver metastasis in pancreatic cancer]]> https://www.researchpad.co/product?articleinfo=N051ebf34-1bbb-487c-976e-de519688d205

Abstract

Purpose

The diagnostic value of nomogram in pancreatic cancer (PC) with liver metastasis (PCLM) is still largely unknown. We sought to develop and validate a novel nomogram for the prediction of liver metastasis in patients with PC.

Method

About 604 pathologically confirmed PC patients from the Sun Yat‐sen University Cancer Center (SYSUCC) between July, 2001 and December, 2013 were retrospectively studied. The SYSUCC cohort was randomly assigned to as the training set and internal validation set. Using these two sets, we derived and validated a prognostic model by using concordance index and calibration curves. Another two independent cohorts between August, 2002 and December, 2013 from the Sun Yat‐sen Memorial Hospital (SYSMH, n = 335) and Guangdong General Hospital (GDGH, n = 503) was used for external validation.

Result

Computed tomography (CT) reported liver metastasis status, carcinoembryonic antigen (CEA) level and differentiation type were identified as risk factors for PCLM in the training set. The final diagnostic model demonstrated good calibration and discrimination with a concordance index of 0.97 and had a robust internal validation. The score ability to diagnose PCLM was further externally validated in SYSMH and GDGH with a concordance index of 0.93. The model showed better calibration and discrimination than CT, CEA and differentiation in each cohort.

Conclusion

Based on a large multi‐institution database and on the routinely observed CT‐reported status, CEA level and tumor differentiation in clinical practice, we developed and validated a novel nomogram to predict PLCM.

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<![CDATA[Cancer patients’ experiences with immune checkpoint modulators: A qualitative study]]> https://www.researchpad.co/product?articleinfo=N19ab7673-a423-414f-be5a-f3671488bac7

Abstract

Background

Minimal qualitative data exist on the experiences of cancer patients treated with immune checkpoint inhibitors or costimulatory antibodies. Understanding the day to day experiences of patients being treated with immune checkpoint modulators, and how these relate to their health‐related quality of life, can inform future research and lead to better clinical decision‐making and care. We report here the first in depth qualitative study to consider patients' diverse and complex experiences with immune checkpoint modulators, with a focus on side effects and how these impact daily life.

Methods

This single‐center qualitative study was based on focus groups and semistructured interviews. Patients who were being treated or who had been treated with immune checkpoint modulators within the last year for a range of cancer diagnoses were recruited. Interpretive description informed our inductive, iterative approach to analysis.

Results

Eight themes were identified, characterizing the complexity of these patients' lived experiences: major categories of side effects experienced and how they impacted patient well‐being; the heterogeneous nature of side effects experienced; living with uncertainty; reframing the meaning and severity of SEs; focus on survival, hope, and being positive; acceptance and adaptation; feeling supported; and faith in medical innovation. Throughout their accounts, participants highlighted the profound impact that immune checkpoint modulators had on their daily lives.

Conclusion

This is the first in‐depth qualitative study into patient accounts of their experiences of treatment with immune checkpoint modulators, related side effects, and how it impacted their daily lives. This research is an integral initial step in developing an instrument that will assess treatment‐related side effects in patients treated with this form of therapy.

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<![CDATA[Real‐world data of lapatinib and treatment after lapatinib in patients with previously treated HER2‐positive metastatic breast cancer: A multicenter, retrospective study]]> https://www.researchpad.co/product?articleinfo=Nca86770c-6cdb-43a0-8b83-f8ea1b31ca78

Abstract

Lapatinib is widely used in the later lines treatment of HER2 positive metastatic breast cancer (MBC). EGF104900 study suggested that among patients who experienced progression on prior trastuzumab‐containing regimens, lapatinib plus trastuzumab had better effects than trastuzumab alone. However, no evidence was discovered in terms of lapatinib plus capetabine compared with lapatinib plus trastuzumab plus chemotherapy, as well as a treatment after progression on lapatinib. We evaluated the medical records retrospectively of all MBC patients with HER2 positive disease who progressed on prior trastuzumab‐containing regimens (advanced setting) and a taxane (any setting) and received lapatinib‐based treatment from 2015 to 2018 in five institutions in China. A total of 242 patients were available for analysis. Among them, 164 (68%) patients received lapatinib plus capetabine (LX) and 78 (32%) patients received lapatinib plus trastuzumab and one chemotherapy (HLC). The median progression‐free survival (PFS) of the HLC group was significantly superior to the LX group (8.8 months vs 5.0 months, P < .0000001). No significant difference in grade 3 or worse adverse events was observed in two groups (P = .57). A total of 175 patients were available for the analysis of the postlapatinib treatment. Continuation of lapatinib showed superior mPFS results compared to the non‐anti‐HER2 treatment (4 months vs 2 months, P = .01) and similar results compared to switch to other anti‐HER2 treatments (4 months vs 4 months, P = .88). In patients who had progressed on prior trastuzumab‐base therapy, HLC provided a new dual‐targeting treatment option for the later lines therapy of patients with HER2 positive MBC. Moreover, evidence of cross‐line use of lapatinib was provided.

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<![CDATA[Surveillance and outcomes after curative resection for gastroesophageal adenocarcinoma]]> https://www.researchpad.co/product?articleinfo=N1516b8c7-4a27-428d-966c-41ef111a040a

Abstract

Background

The goal of surveillance testing is to enable curative salvage therapy through early disease detection, however supporting evidence in gastroesophageal adenocarcinoma is limited. We evaluated frequency of successful salvage therapy and outcomes in patients who underwent surveillance.

Methods

A single‐site, retrospective cohort study was conducted to identify all patients who received curative resection for gastroesophageal adenocarcinoma. Surveillance testing were those investigations not triggered by abnormal symptoms, physical examination, or blood tests. Successful salvage therapy was any potentially curative therapy for disease recurrence which resulted in postrecurrence disease‐free survival ≥2 years. Time‐to‐event data were analyzed using the Kaplan‐Meier method and log rank tests.

Results

Between 2011 and 2016, 210 consecutive patients were reviewed. Esophageal (14%), gastroesophageal junction (40%), and gastric adenocarcinomas (45%) were treated with surgery alone (29%) or multimodality therapy (71%). Adjuvant therapy was administered in 35%. At median follow‐up of 38.3 months, 5‐year overall survival (OS) rate was 56%. Among 97 recurrences, 53% were surveillance‐detected, and 46% were symptomatic. None was detected by surveillance endoscopy. Median time‐to‐recurrence (TTR) was 14.8 months. Recurrences included locoregional only (4%), distant (86%), and both (10%). Salvage therapy was attempted in 15 patients, 4 were successful. Compared to symptomatic recurrences, patients with surveillance‐detected recurrences had longer median OS (36.2 vs 23.7 months, P = .004) and postrecurrence survival (PRS, 16.5 vs 4.6 months, P < .001), but similar TTR (16.2 vs 13.3 months, P = .40) and duration of palliative chemotherapy (3.9 vs 3.3 months, P = .64).

Conclusions

Among patients surveyed, 96% of recurrences were distant, and salvage therapy was successful in only 1.9% of patients. Longer OS in patients with surveillance‐detected compared to symptomatic recurrences was not associated with significant earlier disease detection, and may be contributed by differences in disease biology. Further prospective data are warranted to establish the benefit of surveillance testing in gastroesophageal adenocarcinoma.

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<![CDATA[Inferior prognosis of gastric involvement in patients with gastrointestinal Burkitt Lymphoma]]> https://www.researchpad.co/product?articleinfo=Nb90efc8b-4136-4c76-bb15-6a9c6a69526e

Abstract

Due to limited information reported on the clinical characteristics and outcomes of Burkitt lymphoma (BL) patients with gastrointestinal (GI) involvement, here we used the Surveillance, Epidemiology, and End Results (SEER) database to perform our study in a population‐based scale. Extranodal GI involvement was categorized into gastric and intestinal primary sites. A total of 477 BL patients with GI involvement extracted from the SEER database between 2004 and 2015 were included in this study, 112 (23.5%) with the stomach and 365 (76.5%) with the intestine. Our study demonstrated that gastric involvement, older age, male gender, black race, advanced‐stage III/IV, no‐chemotherapy, and earlier years of diagnosis were associated with a significantly worse overall survival (OS) in GI BL patients after adjustment in multivariate analysis, whereas marital status did not significantly influence OS. Notably, BL Patients with gastric involvement had a significantly inferior 5‐year OS in both univariate and multivariate analysis, as compared to those with intestinal involvement (37.8% vs. 70.2%; Univariate: HR = 2.637, P < .001; Multivariate: HR = 1.489, P = .016). In subgroup analysis, we demonstrated that gastric BL patients had a consistently worse OS than intestinal patients regardless of gender, clinical stage and year of diagnosis. Hopefully, with the advances in modern therapy, improved survival has been found in BL patients with GI involvement as a whole, specifically those with gastric involvement (HR = 0.529, P = .011) in recent years of diagnosis. In conclusion, despite the improved survival achieved in recent years, the prognosis of BL patients with gastric involvement is still poor. Novel personalized therapies and better access to intensive care remain to be needed.

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<![CDATA[Differences in physician opinions about controversial issues surrounding contralateral prophylactic mastectomy (CPM): A survey of physicians from accredited breast centers in the United States]]> https://www.researchpad.co/product?articleinfo=Ndf5b7780-3dd9-4c4e-89b3-73350c941000

Abstract

Background

Indications and insurance coverage for contralateral prophylactic mastectomy (CPM) and CPM as a quality measure are controversial. Few studies have examined physician opinions on these issues.

Methods

A cross‐sectional survey of multi‐specialty physicians at the National Accreditation Program for Breast Centers from 2017‐2018 examined opinions on insurance coverage for CPM, CPM as a quality measure, and indications for CPM. A multivariate logistic regression was used to assess physician and facility factors associated with likelihood to recommend CPM.

Results

Of 2412 physicians, 1226 responded from 382 facilities for a physician response rate of 50.8%. There were 300 (24.5%) medical oncologists, 316 (25.8%) radiation oncologists, 248 (20.2%) plastic surgeons, and 322 (26.3%) oncologic or general surgeons. Three hundred and ninety‐eight (37%) physicians favor insurance coverage for all patients and 520 (46.6%) for patients at average CBC risk. Four hundred and fifty (40%) of all physicians felt physician specific rates of CPM should be a hospital quality measure. BRCA deleterious mutation carrier status was the most common indication to recommend CPM (n = 1043; 92%) and 684 (60.2%) physicians discourage CPM for average contralateral risk (CBC) patients. After adjusting for physician and facility factors, the only significant predictor of higher likelihood to recommend CPM for average CBC risk patients were plastics surgeons (OR = 8.3 (95%CI 2.4‐29.1)) P = .0009).

Conclusion

There is consensus among physicians on the most appropriate indication for CPM but opinions vary on CPM as a quality measure and insurance coverage for CPM. These findings can help guide discussions on CPM among a multidisciplinary team of physicians.

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<![CDATA[Once‐a‐week or every‐other‐day urethra‐sparing prostate cancer stereotactic body radiotherapy, a randomized phase II trial: 18 months follow‐up results]]> https://www.researchpad.co/product?articleinfo=N95fa2768-1714-48b1-b9ee-c8c5c8dc0d86

Abstract

Background

To present the 18 months results from a prospective multicenter phase II randomized trial of short vs protracted urethra‐sparing stereotactic body radiotherapy (SBRT) for localized prostate cancer (PCa).

Methods

Between 2012 and 2015, a total of 170 PCa patients were randomized to 36.25 Gy in 5 fractions (6.5 Gy × 5 to the urethra) delivered either every other day (EOD, arm A, n = 84) or once a week (QW, arm B, n = 86). Genitourinary (GU) and gastrointestinal (GI) toxicity (CTCAE v4.0 scale), IPSS, and QoL scores were assessed at baseline, at the 5th fraction (5fx), 12th weeks (12W), and every 6 months after SBRT. The primary endpoint was biochemical control at 18 months and grade ≥ 3 toxicity (including grade ≥ 2 for urinary obstruction/retention) during the first 3 months.

Results

Among the 165 patients analyzed, the toxicity stopping rule was never activated during the acute phase. Maximum acute grade 2 GU toxicity rates at 5fx were 17% and 19% for arms A and B, respectively, with only 2 cases of grade 2 GI toxicity at 5fx in arm A. At month 18, grade ≥ 2 GU and GI toxicity decreased below 5% and 2% for both arms. No changes in EORTC QLQ‐PR25 scores for GU, GI, and sexual domains were observed in both arms between baseline and month 18. Four biochemical failures were observed, 2 in each arm, rejecting the null hypothesis of an unfavorable response rate ≤ 85% in favor of an acceptable ≥ 95% rate.

Conclusions

At 18 months, urethra‐sparing SBRT showed a low toxicity profile, with minimal impact on QoL and favorable biochemical control rates, regardless of overall treatment time (EOD vs QW).

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<![CDATA[Efficacy of adjuvant chemotherapy with S-1 in stage II oral squamous cell carcinoma patients: A comparative study using the propensity score matching method]]> https://www.researchpad.co/product?articleinfo=N83ad1f15-cdbb-4f4c-8d9c-388a45a97cce

It has been reported that 20% of early-stage oral squamous cell carcinoma (OSCC) patients treated with surgery alone (SA) may exhibit postoperative relapse within 2–3 years and have poor prognoses. We aimed to determine the safety of S-1 adjuvant chemotherapy and the potential differences in the disease-free survival (DFS) between patients with T2N0 (stage II) OSCC treated with S-1 adjuvant therapy (S-1) and those treated with SA. This single-center retrospective cohort study was conducted at Kumamoto University, between April 2004 and March 2012, and included 95 patients with stage II OSCC. The overall cohort (OC), and propensity score-matched cohort (PSMC) were analyzed. In the OC, 71 and 24 patients received SA and S-1, respectively. The time to relapse (TTR), DFS, and overall survival were better in the S-1 group, but the difference was not significant. In the PSMC, 20 patients each received SA and S-1. The TTR was significantly lower in the S-1 group than in the SA group, while the DFS was significantly improved in the former. S-1 adjuvant chemotherapy may be more effective than SA in early-stage OSCC.

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<![CDATA[SlicerDMRI: Diffusion MRI and Tractography Research Software for Brain Cancer Surgery Planning and Visualization]]> https://www.researchpad.co/product?articleinfo=N5117ff89-1cc2-489b-9f6c-323db140a822

PURPOSE

We present SlicerDMRI, an open-source software suite that enables research using diffusion magnetic resonance imaging (dMRI), the only modality that can map the white matter connections of the living human brain. SlicerDMRI enables analysis and visualization of dMRI data and is aimed at the needs of clinical research users. SlicerDMRI is built upon and deeply integrated with 3D Slicer, a National Institutes of Health–supported open-source platform for medical image informatics, image processing, and three-dimensional visualization. Integration with 3D Slicer provides many features of interest to cancer researchers, such as real-time integration with neuronavigation equipment, intraoperative imaging modalities, and multimodal data fusion. One key application of SlicerDMRI is in neurosurgery research, where brain mapping using dMRI can provide patient-specific maps of critical brain connections as well as insight into the tissue microstructure that surrounds brain tumors.

PATIENTS AND METHODS

In this article, we focus on a demonstration of SlicerDMRI as an informatics tool to enable end-to-end dMRI analyses in two retrospective imaging data sets from patients with high-grade glioma. Analyses demonstrated here include conventional diffusion tensor analysis, advanced multifiber tractography, automated identification of critical fiber tracts, and integration of multimodal imagery with dMRI.

RESULTS

We illustrate the ability of SlicerDMRI to perform both conventional and advanced dMRI analyses as well as to enable multimodal image analysis and visualization. We provide an overview of the clinical rationale for each analysis along with pointers to the SlicerDMRI tools used in each.

CONCLUSION

SlicerDMRI provides open-source and clinician-accessible research software tools for dMRI analysis. SlicerDMRI is available for easy automated installation through the 3D Slicer Extension Manager.

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<![CDATA[CIViCpy: A Python Software Development and Analysis Toolkit for the CIViC Knowledgebase]]> https://www.researchpad.co/product?articleinfo=N2b318ddc-a380-44cd-9624-77c382823503

PURPOSE

Precision oncology depends on the matching of tumor variants to relevant knowledge describing the clinical significance of those variants. We recently developed the Clinical Interpretations for Variants in Cancer (CIViC; civicdb.org) crowd-sourced, expert-moderated, and open-access knowledgebase. CIViC provides a structured framework for evaluating genomic variants of various types (eg, fusions, single-nucleotide variants) for their therapeutic, prognostic, predisposing, diagnostic, or functional utility. CIViC has a documented application programming interface for accessing CIViC records: assertions, evidence, variants, and genes. Third-party tools that analyze or access the contents of this knowledgebase programmatically must leverage this application programming interface, often reimplementing redundant functionality in the pursuit of common analysis tasks that are beyond the scope of the CIViC Web application.

METHODS

To address this limitation, we developed CIViCpy (civicpy.org), a software development kit for extracting and analyzing the contents of the CIViC knowledgebase. CIViCpy enables users to query CIViC content as dynamic objects in Python. We assess the viability of CIViCpy as a tool for advancing individualized patient care by using it to systematically match CIViC evidence to observed variants in patient cancer samples.

RESULTS

We used CIViCpy to evaluate variants from 59,437 sequenced tumors of the American Association for Cancer Research Project GENIE data set. We demonstrate that CIViCpy enables annotation of > 1,200 variants per second, resulting in precise variant matches to CIViC level A (professional guideline) or B (clinical trial) evidence for 38.6% of tumors.

CONCLUSION

The clinical interpretation of genomic variants in cancers requires high-throughput tools for interoperability and analysis of variant interpretation knowledge. These needs are met by CIViCpy, a software development kit for downstream applications and rapid analysis. CIViCpy is fully documented, open-source, and available free online.

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