bluuebunny/crossref_metadata_2025 huggingface dataset:
The evolution of barred galaxies in the EAGLE simulations
Authors: Cavanagh Mitchell K , Bekki Kenji , Groves Brent A , Pfeffer Joel
Published: January 2022

We study the morphologies of 3964 galaxies and their progenitors with M⋆ > 1010M⊙ in the reference eagle hydrodynamical simulation from redshifts z = 1 to 0, concentrating on the redshift evolution of the bar fraction. We apply two convolutional neural networks (CNNs) to classify 35 082 synthetic g-band images across 10 snapshots in redshift. We identify galaxies as either barred or unbarred, while also classifying each sample into one of four morphological types: elliptical (E), lenticular (S0), spiral (Sp), and irregular/miscellaneous (IrrM). We find that the bar fraction is roughly constant between z = 0.0 and 0.5 (32–33 per cent), before exhibiting a general decline to 26 per cent out to z = 1. The bar fraction is highest in spiral galaxies, from 49 per cent at z = 0 to 39 per cent at z = 1. The bar fraction in S0s is lower, ranging from 22 to 18 per cent, with similar values for the miscellaneous category. Under 5 per cent of ellipticals were classified as barred. We find that the bar fraction is highest in low-mass galaxies (M⋆ ≤ 1010.5M⊙). Through tracking the evolution of galaxies across each snapshot, we find that some barred galaxies undergo episodes of bar creation, destruction and regeneration, with a mean bar lifetime of 2.24 Gyr. We further find that incidences of bar destruction are more commonly linked to major merging, while minor merging and accretion is linked to both bar creation and destruction.
High-redshift predictions from IllustrisTNG – III. Infrared luminosity functions, obscured star formation, and dust temperature of high-redshift galaxies
Authors: Shen Xuejian , Vogelsberger Mark , Nelson Dylan , Tacchella Sandro , Hernquist Lars , Springel Volker , Marinacci Federico , Torrey Paul
Published: January 2022

We post-process galaxies in the IllustrisTNG simulations with skirt radiative transfer calculations to make predictions for the rest-frame near-infrared (NIR) and far-infrared (FIR) properties of galaxies at z ≥ 4. The rest-frame K- and z-band galaxy luminosity functions from TNG are overall consistent with observations, despite ${\sim}0.5\, \mathrm{dex}$ underprediction at z = 4 for MK ≲ −25 and Mz ≲ −24. Predictions for the JWST MIRI observed galaxy luminosity functions and number counts are given. Based on theoretical estimations, we show that the next-generation survey conducted by JWST can detect 500 (30) galaxies in F1000W in a survey area of $500\, {\rm arcmin}^{2}$ at z = 6 (z = 8). As opposed to the consistency in the UV, optical, and NIR, we find that TNG, combined with our dust modelling choices, significantly underpredicts the abundance of most dust-obscured and thus most luminous FIR galaxies. As a result, the obscured cosmic star formation rate density (SFRD) and the SFRD contributed by optical/NIR dark objects are underpredicted. The discrepancies discovered here could provide new constraints on the sub-grid feedback models, or the dust contents, of simulations. Meanwhile, although the TNG predicted dust temperature and its relations with IR luminosity and redshift are qualitatively consistent with observations, the peak dust temperature of z ≥ 6 galaxies are overestimated by about $20\, {\rm K}$. This could be related to the limited mass resolution of our simulations to fully resolve the porosity of the interstellar medium (or specifically its dust content) at these redshifts.
Investigating Galactic binary cluster candidates with Gaia EDR3
Authors: Angelo M S , Santos J F C , Maia F F S , Corradi W J B
Published: January 2022

A number of stellar open cluster (OC) pairs in the Milky Way occupy similar positions in the phase space (coordinates, parallax, and proper motions) and therefore may constitute physically interacting systems. The characterization of such objects based on observational data is a fundamental step towards a proper understanding of their physical status and to investigate cluster pair formation in the Galaxy. In this work, we employed the Gaia EDR3 data to investigate a set of 16 OCs distributed as 7 stellar aggregates. We determined structural parameters and applied a decontamination technique that allowed us to obtain unambiguous lists of member stars. The studied OCs span Galactocentric distances and ages in the ranges of $7\lesssim \, R_\mathrm{ G}(\textrm {kpc})\lesssim 11$ and $7.3\le \textrm {log}\, t\le 9.2$. Eight OCs were found to constitute four gravitationally bound pairs (NGC 5617–Trumpler 22, Collinder 394–NGC 6716, Ruprecht 100–Ruprecht 101, and NGC 659–NGC 663, the latter being a dynamically unevolved binary) and other four clusters constitute two interacting, but gravitationally unbound, pairs (King 16–Berkeley 4 and NGC 2383–NGC 2384, the latter being a dissolving OC). Other four OCs (Dias 1, Pismis 19, Czernik 20, and NGC 1857) seem not associated with any stellar aggregates. Apparently, clusters within bound and dynamically evolved pairs tend to present ratios of half-light to tidal radius larger than single clusters located at similar RG, suggesting that mutual tidal interactions may possibly affect their structural parameters. Unbound or dynamically unevolved systems seem to present less noticeable signature of tidal forces on their structure. Moreover, the core radius seems more importantly correlated with the clusters’ internal dynamical relaxation process.
Comparison of the Seventh and Eighth Edition of American Joint Committee on Cancer (AJCC) Staging for Selected and Nonselected Oropharyngeal Squamous Cell Carcinomas
Authors: Vijayvargiya Pooja , Trivedi Sumita , Rupji Manali , Song Haocan , Liu Yuan , Jiang Renjian , Kaka Azeem S , Chen Georgia Z , Stokes William , Steuer Conor , Shin Dong M , Beitler Jonathan J , Patel Mihir R , Aiken Ashley , Saba Nabil F
Published: January 2022

Objectives

The eighth edition American Joint Committee on Cancer (AJCC) Staging incorporates significant changes to the seventh edition in the staging of oropharyngeal squamous cell carcinomas (OPSCC). An important change was the inclusion of OPSCC associated with the human papilloma virus (HPV). Our goal is to compare the performance of both staging systems for patients with HPV-selected and unselected clinical characteristics for OPSCC.

Methods

Using the Surveillance, Epidemiology, and End Results (SEER) database, 2004-2016, we identified patients with likely HPV-associated OPSCC based on surrogate markers (white males aged <65 years old with squamous cell carcinomas of the tonsil and base of tongue), excluding those who underwent surgery. We re-classified these patients using seventh and eighth edition staging for HPV-selected OPSCC and compared the prediction performance of both staging editions for overall survival (OS) and disease-specific survival (DSS). We performed the same analysis for clinically unselected patients with OPSCC.

Results

Our analysis included 9554 patients with a median follow-up of 67 months. Comparing the eighth versus seventh edition for our HPV-selected cohort, clinical staging changed for 92.3% of patients and 10-year OS was 62.2%, 61.2%, 35.3%, and 15.5% for Stage I, II, III, and IV, versus 52.9%, 59.2%, 61.6%, 55.1%, 38.3%, and 15.5% for stage I, II, III, IVA, IVB, and IVC, respectively. A similar pattern was observed for 10-year DSS. The concordance statistics for our HPV-selected cohort were improved for both AJCC 7 (0.6260) and AJCC 8 (0.6846) compared with the unselected cohort, 0.5860 and 0.6457 for AJCC 7 and 8, respectively.

Conclusion

The overall performance of discrimination improved from AJCC 7 to AJCC 8 for both clinically selected and unselected patients, but more notably for our HPV-selected cohort. Despite the lack of statistically significant differentiation between Stages I and II in AJCC 8 in either groups, markedly improved discrimination was observed between Stages I/II, III, and IV in the HPV-selected cohort.
Liquid Biopsy Testing for the Management of Patient with Non-Small Cell Lung Cancer Carrying a Rare Exon-20 EGFR Insertion
Authors: Morabito Alessandro , Manzo Anna , Montanino Agnese , Rachiglio Anna Maria , Sforza Vincenzo , Pasquale Raffaella , Costanzo Raffaele , Maiello Monica R , Sandomenico Claudia , Gallo Marianna , Palumbo Giuliano , De Luca Antonella , La Rocca Antonello , Martucci Nicola , De Cecio Rossella , Picone Carmine , Lastoria Secondo , Normanno Nicola
Published: January 2022

Increasing evidence suggests that liquid biopsy might play a relevant role in the management of metastatic non-small cell lung cancer (NSCLC) patients. Here, we show how the Molecular Tumor Board (MTB) in our cancer center employed liquid biopsy to support therapeutic decisions in a patient with NSCLC carrying a rare EGFR mutation. A 44-year-old woman, never-smoker with an EGFR, ALK, and ROS1-negative lung adenocarcinoma and multiple brain metastases received systemic therapy and surgery before being referred to our Institute. The MTB suggested NGS testing of tumor biopsy that revealed a rare exon-20 EGFR insertion (p.His773dup; c.2315_2316insCCA) and EGFR amplification. The MTB recommended treatment with erlotinib and follow-up with liquid biopsy, by using both cell-free DNA (cfDNA) and circulating tumor cells (CTCs). An increase of EGFR mutation levels in cfDNA revealed resistance to treatment about 6 months before clinical progression. Extremely low levels of EGFR p.T790M were detected at progression. Based on preclinical data suggesting activity of osimertinib against EGFR exon-20 insertions, the MTB recommended treatment with brain and bone radiotherapy and osimertinib. A dramatic reduction of EGFR mutation levels in the cfDNA was observed after 4 weeks of treatment. The PET scan demonstrated a metabolic partial remission that was maintained for 9 months. This case supports the evidence that liquid biopsy can aid in the management of metastatic NSCLC. It also suggests that treatment with osimertinib might be a therapeutic option in patients with EGFR exon-20 insertions when a clinical trial is not available.
ALK Inhibitors or Chemotherapy for Third Line in ALK-positive NSCLC? Real-world Data
Authors: Moskovitz Mor , Dudnik Elizabeth , Shamai Sivan , Rotenberg Yakir , Popovich-Hadari Noa , Wollner Mira , Zer Alona , Gottfried Maya , Mishaeli Moshe , Rosenberg Shoshana Keren , Onn Amir , Merimsky Ofer , Urban Damien , Peled Nir , Maimon Natalie , Bar Jair
Published: January 2022

Objectives

ALK inhibitors (ALKi) are the standard-of-care treatment for metastatic ALK-rearranged non-small cell lung cancer (NSCLC) in the first- and second-line setting. We conducted a real-world multi-institutional analysis, aiming to compare the efficacy of third-line ALKi versus chemotherapy in these patients.

Methods

Consecutive ALK-positive metastatic NSCLC patients treated with at least one ALKi were identified in the working databases of 7 Israeli oncology centers (the full cohort). Demographic and clinical data were collected. Patients receiving any systemic treatment beyond 2 ALKi comprised the third-line cohort, whether a third ALKi (group A) or chemotherapy (group B). Groups A and B were compared in terms of overall survival (OS) and time-to-next-treatment line (TNT).

Results

At a median follow-up of 41 months (95% confidence interval [CI]: 32-55), 80 (47.1%) have died. Median OS (mOS) in the full cohort (n = 170) was 52 months (95% CI: 32-65). Number of ALKi (hazard ratio [HR] 0.765; 95% CI: 0.61-0.95; P = .024) and age (HR 1.02, 95% CI: 1.01-1.04, P = .009) significantly associated with OS in the full cohort. The third-line cohort included 40 patients, of which 27 were treated with third ALKi (group A) and 13 treated with chemotherapy (group B). mOS from third-line initiation was 27 months in group A (95% CI: 13-NR) and 13 months for group B (95% CI: 3-NR); the difference was not significant (NS; P = .12). Chemotherapy as first line (HR 0.17, 95% CI: 0.05-0.52, P = .002) and a higher number of ALKi (HR 0.38, 95% CI: 0.20-0.86, P = .011) associated significantly with longer OS of the third-line cohort. TNT was 10 months for group A (95% CI: 5-19) and 3 months for group B (95% CI: 0-NR); the difference was NS (P = .079).

Conclusion

We report mature real-world data of more than 4-year mOS in ALK-positive patients. The number of ALKi given was associated with a better outcome. OS and TNT demonstrated a statistically nonsignificant trend for a better outcome in patients receiving a third-line ALKi.
Exercise-based Multimodal Programming: A Treatment Gap for Older Adults with Advanced Cancer
Authors: Small Stephanie D , Bland Kelcey A , Rickard Julia N , Kirkham Amy A
Published: January 2022

This commentary highlights the challenges of clinical trials, especially as related to trials on exercise for older adults with advanced cancer, and comments on the study by Mikkelsen et al.
Toripalimab Plus Paclitaxel and Carboplatin as Neoadjuvant Therapy in Locally Advanced Resectable Esophageal Squamous Cell Carcinoma
Authors: He Wenwu , Leng Xuefeng , Mao Tianqin , Luo Xi , Zhou Lingxiao , Yan Jiaxin , Peng Lin , Fang Qiang , Liu Guangyuan , Wei Xing , Wang Kangning , Wang Chenghao , Zhang Sha , Zhang Xudong , Shen Xudong , Huang Depei , Yi Huan , Bei Ting , She Xueke , Xiao Wenguang , Han Yongtao
Published: January 2022

Introduction

Immune checkpoint inhibitors (ICIs) are effective in the treatment of advanced esophageal squamous cell carcinoma (ESCC); however, their efficacy in locally advanced resectable ESCC and the potential predictive biomarkers have limited data.

Methods

In this study, locally advanced resectable ESCC patients were enrolled and received neoadjuvant toripalimab (240 mg, day 1) plus paclitaxel (135 mg/m2, day 1) and carboplatin (area under the curve 5 mg/mL per min, day 1) in each 3-week cycle for 2 cycles, followed by esophagectomy planned 4-6 weeks after preoperative therapy. The primary endpoints were safety, feasibility, and the major pathological response (MPR) rate; the secondary endpoints were the pathological complete response (pCR) rate, disease-free survival (DFS), and overall survival (OS). Association between molecular signatures/tumor immune microenvironment and treatment response was also explored.

Results

Twenty resectable ESCC patients were enrolled. Treatment-related adverse events (AEs) occurred in all patients (100%), and 4 patients (22.2%) experienced grade 3 or higher treatment-related AEs. Sixteen patients underwent surgery without treatment-related surgical delay, and the R0 resection rate was 87.5% (14/16). Among the 16 patients, the MPR rate was 43.8% (7/16) and the pCR rate was 18.8% (3/16). The abundance of CD8+ T cells in surgical specimens increased (P = .0093), accompanied by a decreased proportion of M2-type tumor-associated macrophages (P = .036) in responders upon neoadjuvant therapy. Responders were associated with higher baseline gene expression levels of CXCL5 (P = .03) and lower baseline levels of CCL19 (P = .017) and UMODL1 (P = .03).

Conclusions

The combination of toripalimab plus paclitaxel and carboplatin is safe, feasible, and effective in locally advanced resectable ESCC, indicating its potential as a neoadjuvant treatment for ESCC.

Clinical Trial registration

NCT04177797
Reinduction of an Anti-EGFR-based First-line Regimen in Patients with RAS Wild-type Metastatic Colorectal Cancer Enrolled in the Valentino Study
Authors: Fucà Giovanni , Raimondi Alessandra , Prisciandaro Michele , Lonardi Sara , Cremolini Chiara , Ratti Margherita , Clavarezza Matteo , Murialdo Roberto , Sartore-Bianchi Andrea , Smiroldo Valeria , Berenato Rosa , Racca Patrizia , Bergamo Francesca , Corallo Salvatore , Di Bartolomeo Maria , de Braud Filippo , Morano Federica , Pietrantonio Filippo
Published: January 2022

Background

In patients with RAS/BRAF wild-type metastatic colorectal cancer (mCRC), growing evidence supports anti-epidermal growth factor receptor (EGFR) retreatment, whereas little is known on the outcomes of anti-EGFR-based reinduction therapy during the upfront strategy.

Methods

We included patients enrolled in the Valentino study who had disease progression and received at least one dose of post-progression therapy. The Kaplan–Meier method and Cox proportional hazards regression were used for the survival analysis. When comparing the outcomes of anti-EGFR-based reinduction versus any second line, a propensity score–based matching was used.

Results

Liver-limited/single site of disease (P < .001 and P = .002), left-sidedness (P = .029), surgery of metastases (P = .003), early tumor shrinkage, and deeper responses (P = .018 and P = .036) were associated with the use of anti-EGFR-based reinduction versus any other second line. All patients treated with reinduction had an anti-EGFR-free interval of at least 3 months. In the propensity score–matched population, progression-free survival (PFS) was similar in the 2 treatment groups, the overall survival (OS) was significantly longer for patients treated with reinduction (P = .029), and the response rate was higher in patients treated with reinduction (P = .033). An oxaliplatin-free interval ≥12 months, left-sidedness, and molecular hyperselection beyond RAS/BRAF were associated with significantly better outcomes after anti-EGFR-based reinduction.

Conclusions

Reinduction strategies with anti-EGFR-based regimens are commonly used in clinical practice. Our data highlight the importance of clinical–molecular selection for re-treatments and the need for prospective strategy trials in selected populations.
Clinical Implication of Simultaneous Intensity-modulated Radiotherapy Boost to Tumor Bed for Cervical Cancer with Full-thickness Stromal Invasion
Authors: Zhang Zongkai , Jiang Long , Bi Rui , Wu Xiaohua , Zhu Jun , Ke Guihao
Published: January 2022

Objective

The objective of this study was to retrospectively explore the clinical implications of simultaneous intensity-modulated radiotherapy (IMRT) boost to the tumor bed in cervical cancer with full-thickness stromal invasion (FTSI).

Patients and Methods

Patients diagnosed with the International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB and IIA cervical cancer with confirmed FTSI were included. Patients received pelvic IMRT from a dose of 50.4 Gy in 28 fractions with (or without) a simultaneous integrated boost (SIB) to 58.8 Gy in 28 fractions for the tumor bed. The progression-free survival (PFS), overall survival (OS), and pelvic-PFS (p-PFS) were analyzed using the Kaplan–Meier method, and independent prognostic factors were explored by Cox regression analyses.

Results

Patients without a tumor bed boost had a poor prognosis. The 5-year OS was 81.3% versus 58.3% and the 5-year PFS rates were 75.0% versus 57.6% (boost vs non-boost). The FIGO stage, pathology, adjuvant chemotherapy, and tumor bed boost were independent factors affecting both the 5-year OS and PFS. Subgroup analysis showed that the SIB group had a higher 5-year OS, PFS, and p-PFS for different stages, lymph node status, and risk groups than the non-SIB group. Recurrence occurred in 268 of 910 (29.5%) patients without SIB and 49 of 293 (16.7%) with SIB. Among patients with recurrence, 113 of 282 (40.1%) in the non-boost group compared with 14 of 51 (23.0%) patients in the boost group had a pelvic recurrence. Tumor bed boost resulted in an increase in the mean radiation dose to the intestine, rectum, and bladder, although there were no differences in the rates of acute and late toxicities between the 2 groups.

Conclusion

Tumor bed boost by external beam radiotherapy (EBRT) is an effective and safe method for patients with FTSI and risk factors. Compared with the standard prophylactic radiation, tumor bed boost by EBRT was not associated with increased acute and late toxicities.
Evaluation of Targeted Next-Generation Sequencing for the Management of Patients Diagnosed with a Cancer of Unknown Primary
Authors: Fusco Michael J , Knepper Todd C , Balliu Juliana , Del Cueto Alex , Laborde Jose M , Hooda Sharjeel M , Brohl Andrew S , Bui Marilyn M , Hicks J Kevin
Published: January 2022

Background

Cancer of unknown primary (CUP) comprises a heterogeneous collection of malignancies that are typically associated with a poor prognosis and a lack of effective treatment options. We retrospectively evaluated the clinical utility of targeted next-generation sequencing (NGS) among CUP patients to assist with diagnosis and identify opportunities for molecularly guided therapy.

Patients and Methods

Patients with a CUP at Moffitt Cancer Center who underwent NGS between January 1, 2014 and December 31, 2019, were eligible for study inclusion. Next-generation sequencing results were assessed to determine the frequency of clinically actionable molecular alterations, and chart reviews were performed to ascertain the number of patients receiving molecularly guided therapy.

Results

Ninety-five CUP patients were identified for analysis. Next-generation sequencing testing identified options for molecularly guided therapy for 55% (n = 52) of patients. Among patients with molecularly guided therapy options, 33% (n = 17) were prescribed a molecularly guided therapy. The median overall survival for those receiving molecularly guided therapy was 23.6 months. Among the evaluable patients, the median duration of treatment for CUP patients (n = 7) receiving molecular-guided therapy as a first-line therapy was 39 weeks. The median duration of treatment for CUP patients (n = 8) treated with molecularly guided therapy in the second- or later-line setting was 13 weeks. Next-generation sequencing results were found to be suggestive of a likely primary tumor type for 15% (n = 14) of patients.

Conclusion

Next-generation sequencing results enabled the identification of treatment options in a majority of patients and assisted with the identification of a likely primary tumor type in a clinically meaningful subset of patients.
GBAS Regulates the Proliferation and Metastasis of Ovarian Cancer Cells by Combining with eEF1A1
Authors: Ning Xin , Shi Guangyue , Ren Sujing , Liu Shuang , Ding Jing , Zhang Ruichun , Li Lianwei , Xie Qin , Xu Wei , Meng Fanling , Ma Rong
Published: January 2022

Background

The glioblastoma-amplified sequence (GBAS) is a newly identified gene that is amplified in approximately 40% of glioblastomas. This article probes into the expression, prognostic significance, and possible pathways of GBAS in ovarian cancer (OC).

Method

Immunohistochemical methods were used to evaluate the expression level of GBAS in OC and its relationship with clinicopathological characteristics and prognosis. Glioblastoma-amplified sequence shRNA was designed to transfect into OC cell lines to silence GBAS expression, then detect the proliferation, apoptosis, and migration ability of the cell. Furthermore, an in vitro tumor formation experiment in mice was constructed to prove the effect of GBAS expression on the growth of OC in vivo. To further study the regulation mechanism of GBAS, we performed co-immunoprecipitation (Co-IP) and shotgun LC-MS mass spectrometry identification.

Results

Immunohistochemistry indicated that GBAS was markedly overexpressed in OC compared with normal ovarian tissue and was associated with lymph node metastasis. Inhibition of GBAS expression can significantly reduce OC cell proliferation, colony formation, promote cell apoptosis, and reduce the ability of cell migration and invasion. In vivo tumor formation experiments showed that the size and weight of tumors in mice after GBAS expression knockdown was significantly smaller. Glioblastoma-amplified sequence may be combined with elongation factor 1 alpha 1 (eEF1A1) to achieve its regulation in OC. Bioinformatics analysis data indicate that GBAS may be a key regulator of mitochondria-associated pathways, therefore controlling cancer progression. MicroRNA-27b, MicroRNA-23a, and MicroRNA-590 may directly targeting GBAS affects the biological behavior of OC cells.

Conclusion

The glioblastoma-amplified sequence may regulate the proliferation and metastasis of OC cells by combining with eEF1A1.
Risk Factors for Hospitalizations Among Older Adults with Gastrointestinal Cancers
Authors: Li Daneng , Sun Can-Lan , Allen Rebecca , Crook Christiana J , Levi Abrahm , Ballena Richard , Klepin Heidi D , Elias Rawad , Mohile Supriya G , Tew William P , Owusu Cynthia , Muss Hyman B , Lichtman Stuart M , Gross Cary P , Chapman Andrew E , Gajra Ajeet , Cohen Harvey J , Katheria Vani , Hurria Arti , Dale William
Published: January 2022

Background

Older adults (≥65 years) with gastrointestinal (GI) cancers who receive chemotherapy are at increased risk of hospitalization caused by treatment-related toxicity. Geriatric assessment (GA) has been previously shown to predict risk of toxicity in older adults undergoing chemotherapy. However, studies incorporating the GA specifically in older adults with GI cancers have been limited. This study sought to identify GA-based risk factors for chemotherapy toxicity–related hospitalization among older adults with GI cancers.

Patients and Methods

We performed a secondary post hoc subgroup analysis of two prospective studies used to develop and validate a GA-based chemotherapy toxicity score. The incidence of unplanned hospitalizations during the course of chemotherapy treatment was determined.

Results

This analysis included 199 patients aged ≥65 years with a diagnosis of GI cancer (85 colorectal, 51 gastric/esophageal, and 63 pancreatic/hepatobiliary). Sixty-five (32.7%) patients had ≥1 hospitalization. Univariate analysis identified sex (female), cardiac comorbidity, stage IV disease, low serum albumin, cancer type (gastric/esophageal), hearing deficits, and polypharmacy as risk factors for hospitalization. Multivariable analyses found that patients who had cardiac comorbidity (OR 2.48, 95% CI 1.13-5.42) were significantly more likely to be hospitalized.

Conclusion

Cardiac comorbidity may be a risk factor for hospitalization in older adults with GI cancers receiving chemotherapy. Further studies with larger sample sizes are warranted to examine the relationship between GA measures and hospitalization in this vulnerable population.
Measurement of Plasma 25-Hydroxyvitamin D Levels Requires Consideration of Ultraviolet Exposure From Sunlight
Authors: Zhou Hong , He Yi-Ren , Liu Liu , Zhu Zhi-Qiang
Published: January 2022

This letter to the editor raises concerns with the methodology of a recently published study that analyzed the role of vitamin D levels in survival outcomes in patients with pancreatic cancer.
The Impact of Reproductive Factors on the Risk of Breast Cancer by ER/PR and HER2: A Multicenter Case-Control Study in Northern and Eastern China
Authors: Xie Fei , Liu Liyuan , Yang Houpu , Liu Miao , Wang Siyuan , Guo Jiajia , Yu Lixiang , Zhou Fei , Wang Fei , Xiang Yujuan , Yu Zhigang , Wang Shu
Published: January 2022

Background

Previous studies have suggested that reproductive factors are associated with breast cancer risk. Breast cancer subtypes have distinct natural characteristics and may also have unique risk profiles. The purpose of this study was to determine whether reproductive factors affect the risk of breast cancer by estrogen receptor (ER)/progesterone receptor (PR) and HER2 status.

Methods

A multicenter, case-control study was conducted. There were 1170 breast cancer patients and 1170 age- and hospital-matched females included in the analysis. Self-reported data were collected about lifestyle behaviors, including reproductive factors. Breast cancer cases were categorized subtypes according to ER, PR, and HER2 expression as HR- positive, HER2-enriched, and triple negative breast cancer (TNBC). Multivariable logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs).

Results

Having ≤1 child increased risk of HR-positive breast cancer (OR 1.882; 95%CI 1.29-2.74), especially in the premenopausal group (OR 2.212; 95%CI 1.23-3.99). Compared with women who first gave birth after age 30 years, earlier age at first birth decreased the risk of HR-positive breast cancer (≤23 years: OR 0.209; 95%CI 0.14-0.30; 24-29 years: OR 0.256; 95%CI 0.18-0.36; P < .001). Compared with those who had an average breastfed/birth period of more than 2 years, those with an average period less than 6 months had an elevated risk of all subtypes (HR positive: OR 2.690; 95%CI 1.71-4.16, P < .001; HER2-enriched: OR 3.779; 95%CI, 1.62-8.79, P = .001; TNBC: OR 2.564; 95%CI 1.11-5.94, P = .022). For postmenopausal patients, shorter period of lifetime menstrual cycles (≤30 years) had an obviously decreased risk in HR-positive cases (OR 0.397; 95%CI 0.22-0.71), while there was no similar appearance in other molecular subtypes.

Conclusion

The results suggest that reproductive behaviors affect risk of breast cancer differently according to ER/PR and HER2 status.
Physician Perceptions of the FDA’s Breakthrough Therapy Designation: An Update
Authors: Paquin Ryan S , Boudewyns Vanessa , O’Donoghue Amie C , Aikin Kathryn J
Published: January 2022

The US Food and Drug Administration developed the Breakthrough Therapy designation to expedite the development and review of drugs that show a clear advantage over available therapy for serious conditions. Prior research has shown that physicians tend to misunderstand that a drug may receive a Breakthrough Therapy designation based on preliminary clinical evidence (eg, effect on a surrogate endpoint or intermediate clinical endpoint that is likely to predict clinical benefit). The objective of this article is to examine whether physicians’ familiarity with and interpretation of the Breakthrough Therapy designation have changed since a survey on the topic was published in 2016. We replicated three of the questions in that study and explored beliefs that a Breakthrough Therapy designation automatically qualifies a drug for accelerated approval. We also draw comparisons by specialization (oncologists vs. primary care physicians). In general, physicians remain more likely than not to misunderstand the Breakthrough Therapy designation.
Factors Associated with Time to Progression and Overall Survival in Patients with De Novo Metastatic Breast Cancer: A Colombian Cohort
Authors: Díaz-Casas Sandra Esperanza , Briceño-Morales Ximena , Puerto-Horta Leidy Juliana , Lehmann-Mosquera Carlos , Orozco-Ospino Martha Cecilia , Guzmán-AbiSaab Luis Hernán , Ángel-Aristizábal Javier , García-Mora Mauricio , Duarte-Torres Carlos Alfonso , Mariño-Lozano Iván Fernando , Briceño-Morales Clara , Sánchez-Pedraza Ricardo
Published: January 2022

Purpose

About 10% of breast cancer (BC) is diagnosed in stage IV. This study sought to identify factors associated with time to progression (TTP) and overall survival (OS) in a cohort of patients diagnosed with de novo metastatic breast cancer (MBC), from a single cancer center in Colombia, given that information on this aspect is limited.

Methodology

An observational, analytical, and retrospective cohort study was carried out. Time to progression and OS rates were estimated using the Kaplan–Meier survival functions. Cox models were developed to assess association between time to progression and time to death, using a group of fixed variables.

Results

Overall, 175 patients were included in the study; 33.7% of patients had luminal B HER2-negative tumors, 49.7% had bone involvement, and 83.4% had multiple metastatic sites. Tumor biology and primary tumor surgery were the variables associated with TTP and OS. Patients with luminal A tumors had the lowest progression and mortality rates (10 per 100 patients/year (95% CI: 5.0-20.0) and 12.6 per 100 patients/year (95% CI: 6.9-22.7), respectively), and patients with triple-negative tumors had the highest progression and mortality rates (40 per 100 patients/year (95% CI: 23.2-68.8) and 44.1 per 100 patients/year (95% CI: 28.1-69.1), respectively). Across the cohort, the median TTP was 2.1 years (95% CI: 1.6; the upper limit cannot be reached) and the median OS was 2.4 years (95% CI: 2-4.3).

Conclusions

In this cohort, patients with luminal A tumors and those who underwent tumor surgery given that they presented clinical benefit (CB) after initial systemic treatment, had the lowest progression and mortality rates. Overall, OS was inferior to other series due to high tumor burden and difficulties in accessing and continuing oncological treatments.
Everolimus-Induced Pneumonitis in Patients with Neuroendocrine Neoplasms: Real-World Study on Risk Factors and Outcomes
Authors: Taboada Rodrigo G , Riechelmann Rachel P , Mauro Carine , Barros Milton , Hubner Richard A , McNamara Mairéad G , Lamarca Angela , Valle Juan W
Published: January 2022

Background

Everolimus-induced pneumonitis (EiP) has been poorly studied in patients with neuroendocrine neoplasms (NEN) outside clinical trials. The aim of this study was to evaluate the incidence, risk factors, and outcomes of EiP in patients with NENs using real-world data.

Methods

Retrospective study of everolimus-treated patients with advanced NENs. Imaging reports were systematically reviewed for the presence of pneumonitis. Clinical features and treatment profiles for EiP were summarized. Overall survival (OS) was calculated from the initiation of everolimus to the date of death or last follow-up using the Kaplan-Meier method.

Results

A total of 122 patients were included. Median age at start of everolimus was 62 (19-86) years, 62% (76/122) were male, and half were from pancreatic origin (62, 51%). Twenty-eight patients (23%) developed EiP: 82% grade (G)1 or G2, 14% G3 and 4% G4. The median time to EiP was 3.6 (0.8-51) months. Primary tumor site, concurrent lung disease, smoking history, and prior therapies were not associated with the onset of EiP. Patients who developed EiP had longer time on everolimus treatment (median 18 months vs 6 months; P = .0018) and OS (77 months vs 52 months; P = .093). Everolimus-induced pneumonitis was a predictor of improved OS by multivariable analysis (HR 0.39, 95% CI 0.19-0.82; P = .013).

Conclusion

Everolimus-induced pneumonitis in the real-world clinical setting is present in one quarter of patients with NENs receiving everolimus and often occurs early. While risk factors for EiP were not identified, patients with EiP had improved survival.
Prevalence ofBRCA1andBRCA2Germline Mutations in Patients of African Descent with Early-Onset and Familial Colombian Breast Cancer
Authors: Vargas Elizabeth , de Deugd Robert , Villegas Victoria E , Gil Fabian , Mora Lina , Viaña Luis Fernando , Bruges Ricardo , Gonzalez Alejandro , Galvis Juan Carlos , Hamann Ute , Torres Diana
Published: January 2022

Background

Pathogenic germline mutations in the BRCA1 and BRCA2 (BRCA1/2) genes contribute to hereditary breast/ovarian cancer (OC) in White/mestizo Colombian women. As there is virtually no genetic data on breast cancer (BC) in Colombians of African descent, we conducted a comprehensive BRCA1/2 mutational analysis of 60 Afro-Colombian families affected by breast/OC.

Materials and Methods

Mutation screening of the complete BRCA1/2 genes for small-scale mutations and large genomic alterations was performed in these families using next-generation sequencing and multiplex ligation-dependent probe amplification analysis.

Results

Four pathogenic germline mutations, including one novel mutation, were identified, comprising 3 in BRCA1 and one in BRCA2. The prevalence of BRCA1/2 mutations, including one BRCA1 founder mutation (c.5123C>A) previously identified in this sample set, was 3.9% (2/51) in female BC-affected families and 33.3% (3/9) in those affected by both breast and OC. Haplotype analysis of 2 BRCA2_c.2701delC carriers (one Afro-Colombian and one previously identified White/mestizo Colombian patient with BC) suggested that the mutation arose in a common ancestor.

Conclusion

Our data showed that 2/5 (40%) mutations (including the one previously identified in this sample set) are shared by White/mestizo Colombian and Afro-Colombian populations. This suggests that these 2 populations are closely related. Nevertheless, variations in the BRCA1/2 mutational spectrum among Afro-Colombian subgroups from different regions of the country were observed, suggesting that specific genetic risk assessment strategies need to be developed.
Perceptions of Hope Among Bereaved Caregivers of Cancer Patients Who Received Early Palliative Care: A Content and Lexicographic Analysis
Authors: Bigi Sarah , Ganfi Vittorio , Borelli Eleonora , Potenza Leonardo , Artioli Fabrizio , Eliardo Sonia , Mucciarini Claudia , Cottafavi Luca , Cruciani Massimiliano , Cacciari Cristina , Odejide Oreofe , Porro Carlo Adolfo , Zimmermann Camilla , Efficace Fabio , Bruera Eduardo , Luppi Mario , Bandieri Elena
Published: January 2022

Background

Oncologists’ fear of taking away hope from patients when proposing early palliative care (EPC) is a barrier to the implementation of this model. This study explores hope perceptions among bereaved caregivers of onco-hematologic patients who received EPC.

Materials and Methods

Open-ended questionnaires were administered to 36 primary caregivers of patients who received EPC (26 solid and 10 hematologic cancer patients; mean age: 51.4 years, range age: 20-74), at 2 cancer centers, 2 months to 3 years after a patient death. Definitions of hope in the caregivers’ narratives were analyzed through a directed approach to content analysis. Results were complemented with automated lexicographic analysis.

Results

Caregivers perceived hope mainly as resilience and as expectations based on what they were told about the patients’ clinical conditions. Their hope was bolstered by trusting relationships with the healthcare teams. EPC interventions were recalled as the major support for hope, both during the illness and after the death of the patient. The automated quantitative lexical analysis provided deeper insights into the links between hope, truth, and trust.

Conclusions

Our findings suggest that telling the truth about an incurable onco-hematologic disease and beginning EPC might be the combination of factors triggering hope in the setting of incurable cancer.
Mucinous Histology Is Associated with Resistance to Anti-EGFR Therapy in Patients with Left-Sided RAS/BRAF Wild-Type Metastatic Colorectal Cancer
Authors: Wang Chongkai , Sandhu Jaideep , Fakih Marwan
Published: January 2022

Background

Limited studies have suggested that mucinous histology is associated an attenuated response to anti-epidermal growth factor receptor (EGFR) therapy.

Methods

We conducted a single-institution, retrospective study to review the anti-EGFR response and the molecular profile of patients with left-sided microsatellite stable RAS/BRAF wild-type mucinous metastatic colorectal cancer.

Results

In comparison to nonmucinous population (n = 98), mucinous histology (n = 20) was associated with a younger age (48 vs 54, P = .02), wild-type APC (80% vs 15.3%, P < .0001), and wild-type TP53 (40% vs 8.2%, P = .001). Guanine nucleotide binding protein, alpha stimulating (GNAS) mutations were exclusively found in mucinous tumors (20% vs 0, P < .0001). Genomic alterations associated with resistance to anti-EGFR therapy, such as ERBB2 amplification, PIK3CA mutation, MAP2K1 mutation, and KRAS amplification, were identified in patients with left-sided RAS/BRAF wild-type mucinous metastatic colorectal cancer. Mucinous histology was not associated with a worse outcome than non-mucinous histology (34.3 vs 42.2 months, P = .85). However, patients with left-sided RAS/BARF wild-type mucinous colorectal cancer treated with first-line anti-EGFR therapy had significantly worse progression-free survival (4 vs 6.5 months, hazard ratio [HR] = 5.3, 95% confidence interval [CI] 1.3-21.7, P = .01) than patients treated with the first-line vascular endothelial growth factor A antibody, bevacizumab. Anti-EGFR therapy was associated with limited responses and a short PFS across all lines of therapy in 12 patients with left-sided RAS/BRAF wild-type mucinous colorectal cancer.

Conclusions

Mucinous histology is associated with diminished benefits from anti-EGFR therapy in patients with left-sided RAS/BRAF wild-type colorectal cancer. These patients should be considered for bevacizumab-based therapy in the first- and second-line settings.
Smoking Is Related to Worse Cancer-related Symptom Burden
Authors: Oswald Laura B , Brownstein Naomi C , Whiting Junmin , Hoogland Aasha I , Saravia Sabrina , Kirtane Kedar , Chung Christine H , Vinci Christine , Gonzalez Brian D , Johnstone Peter A S , Jim Heather S L
Published: January 2022

Background

Cigarette smoking is related to greater cancer incidence, worse cancer-related clinical outcomes, and worse patient quality of life. Few studies have evaluated the role of smoking in patients’ experiences of cancer-related symptom burden. This study examined relationships between smoking and total symptom burden as well as the incidence of severe symptoms among adult cancer patients.

Patients and Methods

Patients at Moffitt Cancer Center completed self-report surveys as part of routine cancer care. Symptom burden was evaluated as the sum of individual symptom ratings (total symptom burden) and the number of symptoms rated severe (incidence of severe symptoms). Zero-inflated negative binomial modeling was used to evaluate the relationships between smoking status (ever vs never smoker) and symptom burden outcomes controlling for relevant sociodemographic and clinical covariates and accounting for the proportion of participants reporting no symptom burden.

Results

This study included 12 571 cancer patients. More than half reported a history of cigarette smoking (n = 6771, 55%). Relative to never smokers, participants with a smoking history had 15% worse expected total symptom burden (ratio = 1.15, 95% confidence interval [CI] 1.11-1.20, P < .001) and 13% more expected severe symptoms (ratio = 1.13, 95% CI 1.05-1.21, P = .001) above and beyond the effects of relevant sociodemographic and clinical characteristics.

Conclusion

Results provide support that smoking is associated with worse cancer symptom burden. More research is needed to evaluate how smoking history (ie, current vs former smoker) and smoking cessation influence cancer symptom burden.
Efficacy and Safety of Cetuximab Dosing (biweekly vs weekly) in Patients with KRAS Wild-type Metastatic Colorectal Cancer: A Meta-analysis
Authors: Parikh Aparna R , Gonzalez-Gugel Elena , Smolyakova Natalia , Jen Min-Hua , Toms Nikki , Lin Yong , Kim Jong Seok , Kopetz Scott
Published: January 2022

Background

Cetuximab 500 mg/m2 biweekly (Q2W) plus chemotherapy is commonly used and recommended by NCCN guidelines. This meta-analysis compares efficacy and safety between Q2W versus weekly (Q1W) cetuximab dosing.

Methods

A systematic literature review was performed on Pubmed and RightFind (2007-2017) for patients with KRAS wild-type mCRC who received Q2W or Q1W cetuximab and other treatments. Observational studies and case reports were excluded. Randomized trials comparing Q2W and Q1W dosing, and single-arm trials with only Q2W schedule were included. CRYSTAL, a phase 3 randomized study with Q1W cetuximab dosing was paired with each single-arm study with a Q2W schedule and reweighted to achieve similar demographic/baseline characteristics. Overall survival (OS) and progression-free survival (PFS) with hazard ratios (HR), overall response rate (ORR) with odds ratios, and risk difference of adverse events of special interest (AESI) between Q2W versus Q1W cetuximab were analyzed.

Results

Five phase 2 studies with cetuximab Q2W/Q1W dosing schedules were identified: CECOG (phase 2; Q2W, n = 77; Q1W, n = 75), NORDIC 7.5 (phase 2; Q2W, n = 152) and NORDIC 7 (arm C of phase 3; Q1W, n = 109), CELINE (n = 60), OPTIMIX (n = 99), and APEC (n = 289) all phase 2, Q2W, single-arm studies paired with CRYSTAL Q1W dosing (n = 303). Efficacy was similar between Q2W versus Q1W administration; OS HR = 0.96, 95% confidence interval (CI) [0.89, 1.04]; PFS HR = 0.96, 95% CI [0.87, 1.05]; ORR odds ratio 1.16, 95% CI [0.96, 1.41]. Mean differences (Q2W-Q1W) across AESI rates were not clinically meaningful with no obvious directionality.

Conclusion

This meta-analysis demonstrated no significant differences in efficacy and safety between Q2W versus Q1W cetuximab administration in mCRC patients.
Impact of a Multidisciplinary Tumor Board on the Care of Patients with Histiocytic Disorders: The Histiocytosis Working Group experience
Authors: Goyal Gaurav , Young Jason R , Abeykoon Jithma P , Shah Mithun V , Bennani N Nora , Sartori-Valinotti Julio C , Vassallo Robert , Ryu Jay H , Tobin W Oliver , Koster Matthew J , Davidge-Pitts Caroline J , Ravindran Aishwarya , Rech Karen L , Go Ronald S
Published: January 2022

Introduction

Histiocytic disorders pose significant diagnostic and management challenges for the clinicians due to diverse clinical manifestations and often non-specific histopathologic findings. Herein, we report the tumor board experience from the first-of-its-kind Histiocytosis Working Group (HWG).

Materials and Methods

The HWG was established in June 2017 and consists of experts from 10 subspecialties that discuss cases in a multidisciplinary format. We present the outcome of tumor board case discussions during the first 2 years since its inception (June 2017-June 2019).

Results

Forty cases with a suspected histiocytic disorder were reviewed at HWG during this time period. Average number of subspecialties involved in HWG case discussion was 5 (range, 2-9). Histiocytosis Working Group tumor board recommendations led to significant changes in the care of 24 (60%) patients. These included change in diagnosis (n = 11, 27%) and change in treatment (n = 13, 33%).

Conclusion

Our report highlights the feasibility of a multidisciplinary tumor board and its impact on outcomes of patients with histiocytic disorders.
Prospective Comparison of Geriatric Assessment and Provider’s Assessment of Older Adults With Metastatic Breast Cancer in the Community
Authors: Seedor Rino S , Meeker Caitlin R , Lewis Bianca , Handorf Elizabeth A , Filchner Kelly A , Varadarajan Ramya , Hensold Jack , Padmanabhan Aruna , Negin Benjamin , Blankstein Kenneth , Chawla Neha R , Song Wei (Frank) , Epstein Jessica , Winn Jennifer , Goldstein Lori J , Dotan Efrat
Published: January 2022

Background

Geriatric assessment (GA) is recommended for evaluating fitness of an older adult with cancer. Our objective was to prospectively evaluate the gaps that exist in the assessment of older adults with metastatic breast cancer (OA-MBC) in community practices (CP).

Methods

Self-administered GA was compared to provider’s assessment (PA) of patients living with MBC aged ≥65 years treated in CP Providers were blinded to the GA results until PA was completed. McNemar’s test was used to detect differences between PA and GA.

Results

One hundred patients were enrolled across 9 CP (median age 73.9). Geriatric assessment detected a total of 356 abnormalities in 96 patients; of which, 223 required interventions. African American and widowed/single patients were more likely to have abnormalities identified by GA. On average, across 100 patients, PA did not detect 25.5% of GA-detected abnormalities, mostly in functional status, social support, nutrition, and cognition. These differences were less pronounced among providers with more clinical experience. Patients with abnormal Timed Up and Go tests more likely had additional abnormalities in other domains, and more abnormalities that were not identified by PA. Providers were “surprised” by GA results in 33% of cases, mainly with cognitive or social support findings, and reported plans for management change for 39% of patients based on GA findings.

Conclusions

Including a GA in the care of OA-MBC in CP is beneficial for the detection of multiple abnormalities not detected by routine PA.