bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Randomized Phase II Trial of mFOLFOX6 + Bevacizumab Alone or with AdCEA Vaccine + Avelumab Immunotherapy for Untreated Metastatic Colorectal Cancer
Authors: Redman Jason M , Tsai Yo-Ting , Weinberg Benjamin A , Donahue Renee N , Gandhy Shruti , Gatti-Mays Margaret E , Abdul Sater Houssein , Bilusic Marijo , Cordes Lisa M , Steinberg Seth M , Marte Jennifer L , Jochems Caroline , Kim Sunnie S , Marshall John L , McMahon Sheri , Redmond Erica , Schlom Jeffrey , Gulley James L , Strauss Julius 
Published: January 2022

Abstract

Background
FOLFOX plus bevacizumab is a standard of care (SOC) for first-line treatment of microsatellite-stable metastatic colorectal cancer (MSS mCRC). This study randomized patients to SOC or SOC plus avelumab (anti-PD-L1) plus CEA-targeted vaccine.

Methods
Patients with untreated MSS mCRC enrolled to a lead-in arm assessing safety of SOC + immuno-oncology agents (IO). Next, patients were randomized to SOC or SOC + IO. The primary endpoint was progression-free survival (PFS). Multiple immune parameters were analyzed.

Results
Six patients enrolled to safety lead-in, 10 randomized to SOC, and 10 to SOC + IO. There was no difference in median PFS comparing SOC versus SOC + IO (8.8 months (95% CI: 3.3-17.0 months) versus 10.1 months (95% CI: 3.6-16.1 months), respectively; hazard ratio 1.061 [P = .91; 95% CI: 0.380-2.966]). The objective response rate was 50% in both arms. Of patients analyzed, most (8/11) who received SOC + IO developed multifunctional CD4+/CD8+ T-cell responses to cascade antigens MUC1 and/or brachyury, compared to 1/8 who received SOC alone (P = .020). We detected post-treatment changes in immune parameters that were distinct to the SOC and SOC + IO treatment arms. Accrual closed after an unplanned analysis predicted a low likelihood of meeting the primary endpoint.

Conclusions
SOC + IO generated multifunctional MUC1- and brachyury-specific CD4+/CD8+ T cells despite concurrent chemotherapy. Although a tumor-directed immune response is necessary for T-cell–mediated antitumor activity, it was not sufficient to improve PFS. Adding agents that increase the number and function of effector cells may be required for clinical benefit.
Tumor Immune-Infiltrate Landscape After Chemo-Radiotherapy in a Case Series of Patients with Non-small Cell Lung Cancer: Pretreatment Predictors and Correlation With Outcome
Authors: Pavan Alberto , Ferro Alessandra , Fortarezza Francesco , Schiavon Marco , Evangelista Laura , Pezzuto Federica , Lunardi Francesca , Frega Stefano , Bonanno Laura , Rea Federico , Guarneri Valentina , Conte PierFranco , Calabrese Fiorella , Pasello Giulia 
Published: January 2022

Abstract

Introduction
Data on tumor immune-milieu after chemo-radiation (CT-RT) are scarce. Noninvasive tools are needed to improve the treatment of non–small cell lung cancer (NSCLC), especially in the locally advanced (LA) setting.

Methods
We collected a series of superior-sulcus (SS)- patients with NSCLC referred to our Institute (2015-2019), eligible for a preoperative CT-RT. We characterized tumor-infiltrating immune cells (TIICs), determined PD-L1-TPS and the residual viable tumor cells (RVTC). Radiological and metabolic responses were reviewed. We calculated pre-surgery neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR).

Results
Eight patients were included. Radiological responses were 6 disease stabilities (SD) and 2 partial responses (PR). Metabolic responses were 4 SD and 4 PR. CD68+-TIICs were correlated with metabolic response and lower RVTC. CD68+-TIICs were associated with higher PLR. Higher PLR values seemed linked with lower RVTC.

Conclusions
These preliminary results could be useful for consolidation treatment selection for patients with LA-NSCLC without evaluable baseline PD-L1 and higher PLR values.
Sorafenib in Dupuytren and Ledderhose Disease
Authors: Schoenfeld Joshua D , Agaram Narasimhan P , Lefkowitz Robert A , Kelly Ciara M , Healey John H , Gounder Mrinal M 
Published: January 2022

Abstract
Palmar and plantar fibromatosis are benign proliferative processes which present as a diffuse thickening or nodules of the hands and/or feet and may lead to flexion contractures, pain, and functional impairment known as Dupuytren and Ledderhose diseases, respectively. Current treatments are noncurative and associated with significant morbidity. Here, we report on the outcomes of 5 patients with advanced disease, no longer surgical candidates, treated with sorafenib. Sorafenib exhibited an expected safety profile. All 5 patients demonstrated objective responses as evaluated by a decrease in tumor size and/or tumor cellularity from baseline and all 5 patients reported subjective pain relief and/or functional improvement. Mechanistically, immunohistochemistry revealed patchy positivity for PDGFRβ, a known target of sorafenib. The outcomes of these 5 patients suggest the safety and efficacy of a relatively well-tolerated oral agent in the treatment of Dupuytren and Ledderhose diseases and suggest the need for future controlled studies.
Perspectives of Young Women With Gynecologic Cancers on Fertility and Fertility Preservation: A Systematic Review
Authors: Gonçalves Vânia , Ferreira Pedro L , Saleh Mona , Tamargo Christina , Quinn Gwendolyn P 
Published: January 2022

Abstract

Background
Gynecologic cancers standard treatment often requires the removal of some reproductive organs, making fertility preservation a complex challenge. Despite heightened oncofertility awareness, knowledge about fertility attitudes and decisions of young patients with gynecologic cancer is scarce. The aim of this systematic review was to highlight what is currently known about knowledge, attitudes, and decisions about fertility, fertility preservation, and parenthood among these patients.

Methods
Peer-reviewed journals published in English were searched in PubMed, Web of Science and EMBASE from January 1, 2000 to July 1, 2020. Childbearing, fertility, fertility preservation, pregnancy, and parenthood attitudes/decisions after gynecologic cancer from women’s perspective were evaluated.

Results
A total of 13 studies comprised the review. Most of the women valued fertility preservation procedures that could be regarded as a means to restore fertility. A unique feature identified was that fertility preservation was seen also as a way to restore gender identity perceived to be lost or threatened during diagnosis and treatment. Fertility counseling was suboptimal, with wide variability among studies reviewed. Comparisons between gynecologic cancers and other cancer types about fertility counseling rates were inconclusive. The potential negative impact of impaired fertility on patients’ mental health and quality of life was also documented.

Conclusions
Fertility and parenthood were important matters in patients’ lives, with the majority of patients expressing positive attitudes toward future childbearing. Results confirm that the inclusion of patients with gynecologic cancer in research studies focusing on this topic still remains low. Additionally, the provision of fertility counseling and referral by health professionals is still suboptimal.
Chemotherapy Resistance in B-ALL with Cryptic NUP214-ABL1 Is Amenable to Kinase Inhibition and Immunotherapy
Authors: Nardi Valentina , McAfee Steven L , Dal Cin Paola , Tsai Harrison K , Amrein Philip C , Hobbs Gabriela S , Brunner Andrew M , Narayan Rupa , Foster Julia , Fathi Amir T , Hock Hanno 
Published: January 2022

Abstract
BCR-ABL1 kinase inhibitors have improved the prognosis of Philadelphia-chromosome-positive (Ph+)-acute lymphoblastic leukemia (ALL). Ph-like (or BCR-ABL1-like) ALL does not express BCR-ABL1 but commonly harbors other genomic alterations of signaling molecules that may be amenable to therapy. Here, we report a case with a NUP214-ABL1 fusion detected at relapse by multiplexed, targeted RNA sequencing. It had escaped conventional molecular work-up at diagnosis, including cytogenetic analysis and fluorescence in situ hybridization for ABL1 rearrangements. The patient had responded poorly to initial multi-agent chemotherapy and inotuzumab immunotherapy at relapse before the fusion was revealed. The addition of dasatinib targeting NUP214-ABL1 to inotuzumab resulted in complete molecular remission, but recurrence occurred rapidly with dasatinib alone. However, deep molecular remission was recaptured with a combination of blinatumomab and ponatinib, so he could proceed to allotransplantation. This case illustrates that next-generation sequencing approaches designed to discover cryptic gene fusions can benefit patients with Ph-like ALL.
Homologous Recombination Deficiency: Concepts, Definitions, and Assays
Authors: Stewart Mark D , Merino Vega Diana , Arend Rebecca C , Baden Jonathan F , Barbash Olena , Beaubier Nike , Collins Grace , French Tim , Ghahramani Negar , Hinson Patsy , Jelinic Petar , Marton Matthew J , McGregor Kimberly , Parsons Jerod , Ramamurthy Lakshman , Sausen Mark , Sokol Ethan S , Stenzinger Albrecht , Stires Hillary , Timms Kirsten M , Turco Diana , Wang Iris , Williams J Andrew , Wong-Ho Elaine , Allen Jeff 
Published: January 2022

AbstractBackgroundHomologous recombination deficiency (HRD) is a phenotype that is characterized by the inability of a cell to effectively repair DNA double-strand breaks using the homologous recombination repair (HRR) pathway. Loss-of-function genes involved in this pathway can sensitize tumors to poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors and platinum-based chemotherapy, which target the destruction of cancer cells by working in concert with HRD through synthetic lethality. However, to identify patients with these tumors, it is vital to understand how to best measure homologous repair (HR) status and to characterize the level of alignment in these measurements across different diagnostic platforms. A key current challenge is that there is no standardized method to define, measure, and report HR status using diagnostics in the clinical setting.MethodsFriends of Cancer Research convened a consortium of project partners from key healthcare sectors to address concerns about the lack of consistency in the way HRD is defined and methods for measuring HR status.ResultsThis publication provides findings from the group’s discussions that identified opportunities to align the definition of HRD and the parameters that contribute to the determination of HR status. The consortium proposed recommendations and best practices to benefit the broader cancer community.ConclusionOverall, this publication provides additional perspectives for scientist, physician, laboratory, and patient communities to contextualize the definition of HRD and various platforms that are used to measure HRD in tumors.
BRAF Mutations Are Associated with Poor Survival Outcomes in Advanced-stage Mismatch Repair-deficient/Microsatellite High Colorectal Cancer
Authors: Tan Elaine , Whiting Junmin , Xie Hao , Imanirad Iman , Carballido Estrella , Felder Seth , Frakes Jessica , Mo Quanxing , Walko Christine , Permuth Jennifer B , Sommerer Katelyn , Kim Richard , Anaya Daniel A , Fleming Jason B , Sahin Ibrahim Halil 
Published: January 2022

Abstract

Background
Mismatch repair-deficient (MMR-D)/microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) is a unique disease entity with growing interest given the rise of young-onset CRC. Given its heterogeneous behavior and potential for highly effective treatment outcomes, we sought to identify the clinical and molecular features that offer prognostic value for MMR-D CRC.

Materials/Methods
This was a retrospective cohort study of patients with metastatic CRC with MMR-D or microsatellite instability in a real-world database. Overall survival (OS) was determined by the date of metastatic disease to date of death with stratification made based on factors including BRAF and RAS mutation status, age, and MMR protein loss type.

Results
There were 1101 patients in the study. Patients with BRAF mutations had worse OS compared with patients with wild-type BRAF with a median survival of 18.9 months versus 33.2 months (hazard ratio [HR] 1.52, 95% confidence interval [CI]: 1.25-1.86, P &lt; .001). Patients with age &gt;50 were found to have decreased OS versus age ≤50 with a median survival of 21.4 months versus 38.7 months (HR 1.66, 95% CI: 1.33-2.07, P &lt; .001). BRAF mutations and age &gt;50 remained significant predictors of OS in multivariate analysis.

Conclusion
BRAF mutations and age &gt;50 are associated with worse survival outcomes for patients with MMR-D mCRC. RAS mutations and specific MMR alterations are not associated with survival outcomes.
First-Line Treatments for Metastatic Clear Cell Renal Cell Carcinoma: An Ever-Enlarging Landscape
Authors: Gulati Shuchi , Labaki Chris , Karachaliou Georgia Sofia , Choueiri Toni K , Zhang Tian 
Published: January 2022

Abstract
Treatment paradigm for metastatic clear cell renal cell carcinoma (mccRCC) has changed dramatically over the recent decades. From cytokines, interleukin-2 and interferon-α to tyrosine kinase inhibitors and mammalian target of rapamycin inhibitors, during the last decade, combinations of immune checkpoint inhibitors have taken over first-line treatment of mccRCC. These combinations are approved based on results from large phase III clinical trials, all of which used sunitinib as the comparator. These trials include CheckMate214 (ipilimumab plus nivolumab), KEYNOTE 426 (pembrolizumab plus axitinib), JAVELIN Renal 101 (avelumab plus axitinib), CheckMate 9ER (nivolumab plus cabozantinib), and the CLEAR study (lenvatinib and pembrolizumab). Results from these studies constitute milestones for newer therapeutic approaches in mccRCC. The broadening spectrum of treatment options for patients with mccRCC with multiple first-line options currently available also means that treating physicians will need to consider each option carefully, balance clinical factors, financial considerations, and weigh toxicity profiles of each drug before deciding the optimal treatment regimen for each individual patient. We describe each frontline treatment option in detail through this review to aid the decision-making process.
Multi-institutional Analysis of the Clinical and Genomic Characteristics of Black Patients with Metastatic Hormone-Sensitive Prostate Cancer
Authors: Freeman Meredith N , Jang Albert , Zhu Jason , Sanati Farhad , Nandagopal Lakshminarayanan , Ravindranathan Deepak , Desai Arpita , Phone Audrey , Nussenzveig Roberto , Jaeger Ellen , Caputo Sydney A , Koshkin Vadim S , Swami Umang , Basu Arnab , Bilen Mehmet A , Agarwal Neeraj , Sartor Oliver , Burgess Earle F , Barata Pedro C 
Published: January 2022

Abstract

Background
The outcomes of metastatic hormone-sensitive prostate cancer (mHSPC) have significantly improved through treatment intensification, yet Black representation in those studies is suboptimal.

Methods
A multi-institutional, retrospective analysis of Black men with mHSPC was conducted, focusing on baseline demographics, treatment patterns, genomic profiles, clinical outcomes including prostate-specific antigen response, time to castrate-resistant prostate cancer (CRPC), and subsequent treatments.

Results
A total of 107 patients, median age 64 years, 62% with de novo metastases at diagnosis and 64% with high-volume disease, were included. Twenty-nine patients (27%) were treated with androgen deprivation therapy (ADT) with and without first generation anti-androgens, while 20%, 38% and 5% received chemotherapy, abiraterone, and enzalutamide, respectively. At time of data cut-off, 57 (54%) patients had developed CRPC, with a median time to CRPC of 25.4 months (95% CI 20.3-30.4). The median time to CRPC was 46.3 months (18.9-73.7) and 23.4 months (18.6-28.2) for patients who received ADT with or without first-generation anti-androgens and treatment intensification, respectively. The 2-year survival rate was 93.3%, and estimated median overall survival of was 74.9 months (95% CI, 68.7-81.0). Most patients (90%) underwent germline testing; the most frequent known alterations were found within the DNA repair group of genes. Somatic testing revealed pathogenic alterations of interest, notably TP53 (24%) and CDK12 (12%).

Conclusion
In our cohort, Black men with mHSPC presented with a high proportion of de novo metastases and high-volume disease. Treatment outcomes were very favorable with ADT-based regimens. The genomic landscape suggests different molecular profile relative to White patients with potential therapeutic implications.
Real-world Treatment Patterns and Reasons for Therapy Selection in Patients with Advanced Hepatocellular Carcinoma in US Oncology Practices
Authors: Klink Andrew J , Marshall Landon Z , Aly Abdalla , Seal Brian , Healey Marcus J , Feinberg Bruce 
Published: January 2022

Abstract

Background
The treatment landscape for advanced hepatocellular carcinoma (aHCC) is rapidly expanding beyond tyrosine kinase inhibitors (TKIs) in the first-line (1L) setting, with multiple TKIs and immune-checkpoint inhibitors (ICIs) now being evaluated in combination. Real-world evidence describing current treatment patterns and reasons for 1L and 2L treatment selection in aHCC is sparse.

Patients and Methods
A retrospective cohort study with a cross-sectional survey element was conducted using Cardinal Health’s Oncology Provider Extended Network. U.S. medical oncologists identified adult aHCC patients initiating 1L systemic therapy between January 1, 2017 and July 31, 2019 and abstracted data from patient medical records. Data included provider characteristics, patient demographics and clinical characteristics, treatment regimens, and physician rationale for treatment regimen choice.

Results
A total of 44 medical oncologists provided data on 284 aHCC patients. The median age at 1L initiation was 61.5 years, and the majority were male (78%) and white (66%). Nearly half (47%) initiated 1L treatment in 2019, 34% were ECOG performance status 2+, and 63% were Child-Pugh Class B/C. Among the 284 aHCC patients, TKIs were used by 94% of patients in the 1L setting, comprised predominantly of sorafenib (54%) and lenvatinib (38%). ICIs were most common among the 90 patients (66%) who received 2L treatment.

Conclusion
In the community-oncology practice setting, nearly all aHCC patients received sorafenib or lenvatinib in the 1L setting, while the majority of patients received an ICI in the 2L setting. With recent ICI approvals in aHCC, this marks the beginning of an increased use of ICIs in the 1L setting.
Impact of the Economic Status of the Patient’s Country of Residence on the Outcome of Oncology Clinical Trials
Authors: Nishiyama Saki , Narukawa Mamoru 
Published: January 2022

Abstract

Background
Prolongation of overall survival (OS) is commonly evaluated as a primary endpoint in confirmative oncology clinical trials; however, it is potentially affected by subsequent treatments carried out in practice. To design and implement multi-regional clinical trials properly, we compared survival outcomes between Organisation for Economic Co-operation and Development (OECD) and non-OECD countries.

Materials and Methods
Individual patient data from industry-sponsored multi-regional phase III oncology trials were obtained from the Project Data Sphere. Patients of each arm were divided into several subgroups based on race and country where patients were enrolled. We defined the member countries of the OECD. Cox regression analysis was conducted to estimate the hazard ratio (HR) for progression-free survival (PFS) and OS between the different subgroups in each trial, followed by a meta-analysis to estimate the summary HR and its confidence interval with a random-effect model.

Results
Eleven arms from 10 clinical trials were eligible for the analysis. No statistically significant difference was observed in PFS and OS between Caucasian and Asian. A prolongation of OS was observed in patients enrolled in the OECD group compared with non-OECD group, while no statistically significant difference was observed in PFS.

Conclusion
The economic status and healthcare environment of countries where patients reside have an impact on the outcome of OS. Clinical trial sponsors are recommended to consider carefully how to properly design oncology clinical trials including the selection of countries and data management of subsequent treatments.
Safety and Efficacy of Bis-Glyceryl Ascorbate as Prophylaxis for Hand-Foot Skin Reaction: A Single-Arm, Open-Label Phase I/II Study (DGA Study)
Authors: Yamamoto Kazuhiro , Nishiyama Satoshi , Kunisada Makoto , Iida Masashi , Ito Takahiro , Ioroi Takeshi , Makimoto Hiroo , Omura Tomohiro , Harada Kenichi , Fujisawa Masato , Nishigori Chikako , Yano Ikuko 
Published: January 2022

Abstract

Background
Hand-foot skin reaction (HFSR) induced by multiple tyrosine kinase inhibitors (TKIs) is a serious side effect that can cause treatment interruption or decreased dosing. This study was conducted to evaluate the safety and efficacy of bis-glyceryl ascorbate (Amitose bis(di)-glyceryl ascorbate [DGA])-containing cream (DGA cream) for the prevention of sunitinib-induced HFSR.

Methods
A single-arm, open-label phase I/II study was conducted, targeting patients with metastatic renal cell carcinoma (mRCC) who were receiving sunitinib therapy with a schedule of 2 weeks on/1 week off. The participants applied DGA cream to both palmar and plantar surfaces in combination with a moisturizing agent as standard-of-care prophylaxis during two sunitinib treatment cycles (6 weeks). The primary endpoint in phase I was safety defined as dermatological abnormalities and it was determined in the first five participants. The primary endpoint in phase II was efficacy defined as development of grade 1 or higher HFSR defined by Common Terminology Criteria for Adverse Events within 6 weeks and it was determined on a full analysis set (FAS) defined as the population including all participants who used DGA cream once in the study duration. Efficacy in the per protocol set (PPS) defined as the population excluding seven patients whose study treatment was interrupted was evaluated as a secondary endpoint.

Results
Twenty-four patients were enrolled as a FAS. No dermatological abnormalities occurred in the first 5 patients enrolled in the phase I study. Three patients developed HFSR (grade 1: n = 2, grade 2: n = 1) in the observation period. The HFSR incidence rate was 12.5% (3/24; 95% confidence interval [CI]: 2.7%-32.4%) in the FAS, which was significantly lower than the incidence rate predefined as a threshold of 33.3% by a previous report from our hospital (P = .030). The incidence rate in the 17 patients of the PPS was 17.6% (3/17; 95%CI: 3.8%-43.4%).

Conclusion
DGA cream may be safe and effective in the prophylaxis of HFSR in mRCC patients who receive sunitinib therapy (Trial ID: jRCTs051180051).