bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

AbstractBackgroundCancer 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 MethodsPatients 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.ResultsNinety-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.ConclusionNext-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

Abstract

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

Abstract

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.
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

Abstract

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 &lt; .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 &lt; .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

Abstract
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

AbstractPurposeAbout 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.MethodologyAn 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.ResultsOverall, 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).ConclusionsIn 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

Abstract

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

AbstractBackgroundPathogenic 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 MethodsMutation 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.ResultsFour 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&gt;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.ConclusionOur 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

Abstract

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

Abstract

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 &lt; .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 &lt; .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.