tbuckley/cabot-search huggingface dataset:
A phase Ib study of the PI3K<b>δ inhibitor linperlisib in patients with advanced solid tumors.</b>
Authors: Jin Li, Nong Xu, Tianshu Liu, Jianjin Huang, Yongmei Yin, Haibo Mou, Jun Zhang, Lihua Wu, Zong liang Liu, Hanying Bao, Zusheng Xu
Journal: Journal of Clinical Oncology (2021)

3099 Background: Phosphatidylinositol-3 kinase (PI3K) pathways are important elements of tumor survival and progression, and PIK3C genes are often mutated or overexpressed in many cancers. Additionally, PIK3D (PI3Kδ) modulates immune cell functions in tumors, elaborating another PI3Kδ inhibition feature with a potential clinical benefit. Linperlisib, an oral and highly selective PI3Kδ inhibitor, demonstrated potent anti-tumor activity in syngeneic animals from previous research. In this Phase 1b study, the safety, tolerability, and efficacy of linperlisib is under investigation for patients with advanced solid tumors. Methods: Linperlisib was given orally once daily (QD) in 28-day cycle until disease progression, unacceptable toxicity, or withdrawal from the study. Adverse events (AEs) were graded by NCI-CTCAE v5.0. Efficacy was assessed according to RECIST1.1 criteria. Results: As of December 28, 2020, 70 patients were enrolled in the Phase1b study, with advanced cancers, including colorectal (n = 22), breast (n = 8), lung (n = 8), kidney (n = 5), liver (n = 4), ovarian (n = 1), head and neck (n = 5), and esophageal (n = 1) cancers; sarcomas, (n = 4), small intestinal stromal tumor (n = 3), thymic (n = 2), gallbladder (n = 2), gastric (n = 4), and pancreatic (n = 1) carcinomas. The patients were heavily pretreated with an average of 4 previous lines of therapy. Among the 70 patients, the most common nonhematologic TEAEs (all grades/grade≥3) were proteinuria (37.14%/0%), elevated aspartate aminotransferase (20%/0%), nausea (20%/0%), oral mucositis (2.8%/2.8%), diarrhea (2.8%/2.8%). The most common hematological TEAEs were leukopenia (24.28%/0%) and neutropenia (17.14%/4.28%). There were no unexpected toxicities in this study. Of 42 patients evaluable for response, the overall response rate was 2.38%. Notably, the disease control rate (DCR) was 45.24% from monotherapy treatment. One patient with thymic carcinoma obtained a partial response (80.8% reduction of the target lesion), with a duration of response of more than 6 cycles. The treatment of this subject is continuing. A lung adenocarcinoma subject reached radiological stable disease associated with 13.7% reduction in the target lesion and disease control for approximately 6 months. Conclusions: In this study, the PI3K inhibitor, linperlisib exhibited a favorable safety profile as was previously seen in lymphoma patients. Monotherapy treatment with linperlisib was observed to impart a high DCR in advanced solid cancers of many types. Available data from linperlisib and other PI3K inhibitors suggests that linperlisib may limit tumor growth directly, but also by affecting the tumor immune microenvironment. With these promising indications of clinical tolerability and activity, further investigation of linperlisib alone or in key therapeutic combinations is warranted. Clinical trial information: NCT04049929.
Outcomes of first-generation versus third-generation epidermal growth factor receptor (EGFR) inhibitors in non-small cell lung cancer with brain metastases (NSCLCBM).
Authors: Vineeth Tatineni, Patrick Joseph O'Shea, Yasmeen Rauf, Xuefei Jia, Erin Sennett Murphy, Samuel T. Chao, John H. Suh, David M. Peereboom, Manmeet Singh Ahluwalia
Journal: Journal of Clinical Oncology (2021)

2031 Background: Non-small cell lung cancer (NSCLC) is the most common cause of brain metastases, with 10-30% of patients developing brain metastases. EGFR is a transmembrane glycoprotein that is mutated in up to 50% of NSCLCs. First-generation EGFR tyrosine kinase inhibitors (TKI), such as erlotinib and gefitinib, are limited by blood-brain barrier (BBB) penetration and exon 20 (T790M) tumor mutations. Third-generation EGFR TKIs, such as osimertinib, have shown better BBB penetration and efficacy against T790M mutations. In this retrospective study, we evaluated the overall survival (OS) and progression-free survival (PFS) in NSCLCBM patients treated with first and third-generation EGFR TKIs. Methods: NSCLCBM patients diagnosed between 2010 and 2019 at our tertiary care center were investigated. Information regarding molecular marker status, systemic therapies, and date of progression were collected. OS was defined as the start date of systemic therapy to the date of last follow-up or death. OS and PFS were estimated by the Cox proportional model. Results: A total of 193 NSCLCBM patients with an EGFR mutation were identified. 33 EGFR mutant patients received first-generation EGFR TKIs, of which 56.7% were females, 82.1% were white, and had a median age of 63.2 years. 22 patients received third-generation EGFR TKIs, 64.1% being female, 76.9% being white, and with a median age of 71.5 years. The median OS (mOS) in patients who received first and third-generation EGFR TKIs was 59.8 months and 65.9 months respectively (p-value (p) = 0.06). The median PFS (mPFS) between the first and third-generation EGFR TKI cohorts was 44.3 months and 66.9 months respectively (p= 0.048, hazard ratio (HR) = 0.50 (95% confidence interval (CI) = 0.25, 0.99). Conclusions: Newer generation of targeted therapies in NSCLCBM have focused on overcoming previous efficacy hurdles, including BBB penetration and resistant mutations. We determined that there was a significant mPFS benefit in osimertinib compared to erlotinib or gefitinib, and a trend towards significant mOS benefit in osimertinib compared to erlotinib or gefitinib in patients with NSCLCBM. However, these results should be interpreted cautiously due to treatment selection bias, and further studies need to be conducted on brain metastases lesion size and response rates.[Table: see text]
Prognostic impact of depth of response in Waldenström macroglobulinemia patients treated with fixed duration chemoimmunotherapy.
Authors: Nirosha D. Perera, Jithma P. Abeykoon, Jorge J. Castillo, Joshua Gustine, Marzia Varettoni, Alessandra Tedeschi, Chiara Cavalloni, Anna Maria Frustaci, Matthew J. Maurer, Prashant Kapoor, Thomas Matthew Habermann, Thomas E. Witzig, Robert A. Kyle, Morie A. Gertz, Steven P. Treon, Stephen M. Ansell, Jonas Paludo
Journal: Journal of Clinical Oncology (2021)

8049 Background: The treatment paradigm of Waldenström macroglobulinemia (WM) continues to evolve as new therapies expand our options for this indolent and incurable disease. While more profound responses are generally associated with longer treatment-free intervals, the impact of depth of response from fixed duration therapy in WM patients' survival needs further evaluation. In this international, multicenter cohort study, we report the prognostic impact of depth of response in WM. Methods: 319 WM patients treated with frontline fixed duration therapy [Dexamethasone/Rituximab/Cyclophosphamide (DRC), Bendamustine/Rituximab (BR), or Bortezomib/Dexamethasone/Rituximab (BDR)] were included. Response at the completion of therapy (6 months) was used in a landmark analysis for progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS) (defined as time from 6 months post treatment response to event or censor). Response was defined by modified IWWM-6 criteria. Associations between clinical variables and outcomes were evaluated using Cox proportional-hazard models. Results: The median age at the time of treatment initiation was 64 years (range: 29-94), 59% were men, and risk category by International Prognostic Scoring System (IPSS)-WM was low (n=67, 23%), intermediate (n=83, 29%), and high-risk (n=141, 48%). Evaluable responses at 6 months from frontline therapy [DRC (n=105; 41%), BR (n=83; 32%), BDR (n=68; 27%)] were available in 256 patients and included in the landmark analysis. Median follow-up was 63 months (95% CI: 59-70). The rate of major response (PR or better) at 6 months was 74% for the entire cohort. Five-year PFS rates from completion of therapy for patients who attained major response vs. those who did not were 71% and 43%, respectively (p&lt;0.001). Five-year TTNT rates for patients who attained major response vs. not were 84% and 54%, respectively (p&lt;0.001). Five-year OS rates for patients who attained major response vs. not were 92% and 77%, respectively (p&lt;0.001). In multivariable analyses including other WM prognostic factors evaluated at initiation of frontline therapy, attaining a major response at 6 months was associated with superior PFS (HR 0.33, p&lt;0.001), TTNT (HR 0.23, p&lt;0.001), and OS (HR 0.31, p=0.001–Table). Conclusions: Achieving a major response at 6 months after frontline chemoimmunotherapy emerges as a significant prognostic factor for PFS, TTNT and OS in patients with WM.[Table: see text]
Cereblon enhancer methylation and IMiD resistance in multiple myeloma
Authors: Larissa Haertle, Santiago Barrio, Umair Munawar, Seungbin Han, Xiang Zhou, Cornelia Vogt, Rafael Alonso Fernández, Max Bittrich, Yanira Ruiz-Heredia, Matteo Da Viá, Josip Zovko, Andoni Garitano-Trojaola, Niccolò Bolli, Anna Ruckdeschel, Thorsten Stühmer, Manik Chatterjee, Miriam Kull, Jan Krönke, Xabier Agirre, Jose I. Martin-Subero, Peter Raab, Hermann Einsele, Leo Rasche, Joaquin Martinez-Lopez, Thomas Haaf, K. Martin Kortüm
Journal: Blood (2021)
Update analysis of NEJ009: Gefitinib alone (G) versus gefitinib plus chemotherapy (GCP) for non-small cell lung cancer with mutated EGFR.
Authors: Eisaku Miyauchi, Satoshi Morita, Atsushi Nakamura, Yukio Hosomi, Kana Watanabe, Satoshi Ikeda, Masahiro Seike, Yuka Fujita, Koichi Minato, Ryo Ko, Toshiyuki Harada, Koichi Hagiwara, Kunihiko Kobayashi, Toshihiro Nukiwa, Akira Inoue
Journal: Journal of Clinical Oncology (2021)

9081 Background: NEJ009 study is the first randomized phase III trial that compared gefitinib plus chemotherapy with gefitinib in patients with untreated NSCLC harboring EGFR mutations. We report an updated OS and long-term tolerability analysis, including subgroup analyses focusing on a type of EGFR mutation and metastatic sites. Methods: Patients were randomly assigned to gefitinib (gefitinib 250 mg PO, QD) and GCP regimen (gefitinib 250 mg PO, QD combined with carboplatin AUC 5 and pemetrexed 500 mg/m2 in a 3-week cycle for up to six cycles, followed by concurrent gefitinib and pemetrexed maintenance). This study tested multiple primary endpoints, PFS, PFS2, and OS, which were analyzed using a preplanned hierarchical sequential testing method. Results: Three hundred forty-five patients were randomly assigned (gefitinib, n = 172; GCP, n =170). At latest data cut-off (May 22, 2020), although there was no significant difference in OS between the groups (HR, 0.82; 95% CI, 0.64 to 1.06; P=0.13), GCP still demonstrated significantly better PFS and PFS2 compared to G. The updated median PFS, PFS2, and OS was 11.2 months, 18.0 months, and 38.5 months in the gefitinib group and 20.9 months, 20.9 months, and 49.0 months in the GCP group, respectively. No severe adverse events occurred in the period since the first report. Conclusions: This updated analysis confirmed that the GCP regimen achieved significantly better PFS and PFS2 with an acceptable safety profile compared with gefitinib alone. The efficacy outcome of GCP is more favorable than gefitinib monotherapy as first-line treatment of NSCLC with EGFR mutation. Clinical trial information: UMIN000006340. Clinical trial information: UMIN000006340. [Table: see text]
Prevalence and predictors of peripheral neuropathy after chemotherapy: Outcomes from the Detroit Research on Cancer Survivorship (ROCS) cohort.
Authors: Kalyan Sreeram, Randell Seaton, Mandana Kamgar, Hadeel Assad, Mark K. Greenwald, Julie J. Ruterbusch, Jennifer Lynn Beebe-Dimmer, Ann G. Schwartz, Michael S. Simon
Journal: Journal of Clinical Oncology (2021)

12069 Background: Increased life expectancy for cancer survivors following advances in treatment has led to a greater likelihood of developing long-term complications. Among them is chemotherapy-induced peripheral neuropathy (CIPN), which adversely impacts the functional capacity of survivors. We assessed prevalence and predictors of CIPN in a cohort of African-American (AA) cancer survivors. Methods: The study population included 633 breast, colorectal, prostate and lung cancer survivors who received chemotherapy and participated in the Detroit Research on Cancer Survivorship (ROCS) study. Presence of CIPN was based on self-reported pain, numbness or tingling in the hands or feet, occurring either for the first time or worsening after chemotherapy. If participants reported continued CIPN at the time of survey, their symptoms were reported as persistent. CIPN severity was self-reported as mild, moderate or severe. Logistic regression analysis was used to evaluate socio-demographic and clinical factors (including 12 common comorbid conditions) associated with CIPN prevalence, persistence and severity. Results: Overall, 67% of the cohort reported CIPN at a mean time of 25.3 months (range 2-74 months) after cancer diagnosis, and 51% reported persistent CIPN. The distribution of CIPN severity consisted of 32.2% with mild, 30.8% with moderate, and 36.9% with moderate to severe symptoms. Diagnosis of primary breast (OR 3.99, 95% CI 1.52-10.46) or colorectal cancers (OR 5.24, 95% CI 2.17-12.69) conferred greater CIPN prevalence relative to a diagnosis of prostate cancer. The presence of each additional comorbid condition among those outlined in the survey also conferred a 20% greater prevalence of CIPN (OR 1.2, 95% CI 1.03-1.39). Similar trends were seen among those who reported persistent CIPN. Using age &gt; 65 at diagnosis as the reference group, age &lt; 50 (OR 2.64, 95% CI 1.43-4.88) and age 51-64 (OR 1.96, 95% CI 1.14-3.35) resulted in an increased risk of moderate or severe compared to mild CIPN. Conclusions: In the Detroit ROCS cohort, CIPN was reported in two-thirds of cancer survivors receiving chemotherapy. Out of them, more than one-third reported moderate to severe symptoms, more commonly seen among those age &lt; 65. Consideration of CIPN as a prominent long-term complication of cancer treatment should play a role in treatment decisions and development of new chemotherapy regimens.
Association of rurality and race with surgical treatment and outcomes for nonmetastatic colon cancer.
Authors: Niveditta Ramkumar, Carrie Colla, Qianfei Wang, James O'Malley, Sandra L. Wong, Gabriel A. Brooks
Journal: Journal of Clinical Oncology (2021)

78 Background: Rural cancer patients face limited access to care due to greater travel distance and lack of specialty cancer care. Little is known about the intersection of rurality with well-documented racial disparities in colon cancer treatment and outcomes. Methods: We used fee-for-service Medicare claims to study patients age 65+ diagnosed with incident colon cancer without evidence of metastases who underwent cancer-directed surgery between 04/01/2016 and 09/30/2018. The primary exposure wasrurality of patient’s residence categorized as metropolitan (metro), micropolitan, and small town/rural. Outcomes were non-elective surgery (emergency department visit or transfer within 2 days prior to surgery), receipt of minimally invasive surgery (laparoscopic or robotic), 90-day surgical complications, and 90-day mortality. Logistic regression adjusted for patient demographics, cancer side (right vs left), comorbidities, and Area Deprivation Index. We assessed effect modification by race/ethnicity. Results: Of 57,710 patients with incident non-metastatic colon cancer, 37,691 (65%) underwent surgery. In this surgical cohort, small town/rural and micropolitan residents were more likely to be older, white, and Medicare-Medicaid dual-eligible than metro residents. After risk adjustment, patients in small town/rural areas had higher odds of non-elective surgery (OR =1.24, 95% CI:1.13-1.36) and lower odds of minimally invasive surgery (OR = 0.75, 95% CI:0.71-0.80) than patients living in metro areas. Similar results were seen for micropolitan areas. White rural patients had lower mortality than white urban patients, whereas black rural patients had higher mortality than black metro patients (see Table). Increasing area deprivation was associated with higher odds of non-elective surgery, surgical complications and mortality, and lower odds of minimally invasive surgery, even after adjusting for race and rurality. Conclusions: Small town/rural-residing Medicare beneficiaries undergoing surgery for non-metastatic colon cancer were less likely to receive optimal surgical management and had worse outcomes, especially among non-white patients. The compounded effect of rurality, race/ethnicity, and social deprivation should be incorporated in developing policies and interventions to improve care for rural cancer patients.[Table: see text]
Socioeconomic background in relation to stage at diagnosis in women with breast cancer.
Authors: Juan Manuel Ariza, Anne Cowppli-Bony, Solenne Billon, Stephanie Ayrault-Piault, Audrey Blanc-Lapierre, Florence Florence Molinie
Journal: Journal of Clinical Oncology (2021)

10574 Background: Breast cancer (BC) has been associated with socioeconomic deprivation and rural residence. However, it’s still unclear how these factors interplay to affect the frequency and incidence of early and advanced BC. Methods: Taking advantage of the Loire-Atlantique/Vendée cancer registry (France), we investigated the association between early (TNM stage &lt; 2) and advanced (TNM stage ≥2) BC and the socio-economic background (SB) of women diagnosed in the study region from 2008 to 2015. Socioeconomic status was studied using the residence information of every patient linked to the European Deprivation Index (EDI), an ecological index constructed to reflect individual deprivation experienced at the smallest geographical unit of France (IRIS = 2000 inhabitants). To investigate SB, we created a composite variable using the EDI and the urban/rural context information, to define 4 categories: affluent-urban, affluent-rural, deprived-urban, and deprived-rural. Two statistical approaches were implemented: i) mixed-effects logistic regression models to examine the likelihood (relative risk, RR) of being diagnosed with advanced BC, and ii) Poisson regression for modeling incidence rates of early and advanced stages. Analyses were stratified by age ( &lt; 45, 45 to 74, &gt; 75 years) with a random intercept at the IRIS level. For the strata 45 to 74, the models were adjusted for organized screening. Results: During the study period, 14,542 BC cases were recorded. Compared to the women diagnosed in the most affluent-urban areas, a higher proportion of cancer diagnosed at an advanced stage was observed in the women living in more deprived-rural areas (aged &lt; 45 years, RR = 1.48 95% CI 1.17 - 1.73; aged 45 to 74 years, RR = 1.22, 95% CI 1.02-1.42; aged &gt; 74 years, RR = 1.08, 95% CI 0.85-1.27). Furthermore, while in the population under 74 years, incidence rates of early BC in deprived-rural women were reduced by 25-85 % in comparison to affluent-urban women (IRR: 0.33 to 0.97 95% CI 0.16 -0.98), the rates of advanced BC were unaffected by deprivation-rurality (Deprived rural vs Affluent urban, IRR: 1.06 to 1.13 95% CI 0.79 -1.72). For the population over 74 years, we were unable to detect any associations between SB and BC incidence by stage at diagnosis. Conclusions: Advanced stage at diagnosis was more frequent among deprived–rural women aged under 74 years and coincided with the low incidence rates of early stages in this population. No disparities in the incidence rates of advanced BC were detected according to their SB in any age classes, suggesting other factors may be stronger contributors to the advanced stage at diagnosis. Future research should investigate whether screening practices may influence the disparities in the early stage at diagnosis for women under 74.
NCI Imaging Data Commons
Authors: Andrey Fedorov, William J.R. Longabaugh, David Pot, David A. Clunie, Steve Pieper, Hugo J.W.L. Aerts, André Homeyer, Rob Lewis, Afshin Akbarzadeh, Dennis Bontempi, William Clifford, Markus D. Herrmann, Henning Höfener, Igor Octaviano, Chad Osborne, Suzanne Paquette, James Petts, Davide Punzo, Madelyn Reyes, Daniela P. Schacherer, Mi Tian, George White, Erik Ziegler, Ilya Shmulevich, Todd Pihl, Ulrike Wagner, Keyvan Farahani, Ron Kikinis
Journal: Cancer Research (2021)

Abstract The National Cancer Institute (NCI) Cancer Research Data Commons (CRDC) aims to establish a national cloud-based data science infrastructure. Imaging Data Commons (IDC) is a new component of CRDC supported by the Cancer Moonshot. The goal of IDC is to enable a broad spectrum of cancer researchers, with and without imaging expertise, to easily access and explore the value of deidentified imaging data and to support integrated analyses with nonimaging data. We achieve this goal by colocating versatile imaging collections with cloud-based computing resources and data exploration, visualization, and analysis tools. The IDC pilot was released in October 2020 and is being continuously populated with radiology and histopathology collections. IDC provides access to curated imaging collections, accompanied by documentation, a user forum, and a growing number of analysis use cases that aim to demonstrate the value of a data commons framework applied to cancer imaging research. Significance: This study introduces NCI Imaging Data Commons, a new repository of the NCI Cancer Research Data Commons, which will support cancer imaging research on the cloud.
Late relapse of germ cell tumors: Detection and treatment outcomes.
Authors: Noah Hunter Richardson, Sandra K. Althouse, Ryan Ashkar, Clint Cary, Timothy A. Masterson, Richard Foster, Nasser H. Hanna, Lawrence H. Einhorn, Nabil Adra
Journal: Journal of Clinical Oncology (2021)

5007 Background: Late relapse (LR) of germ cell tumors (GCT) is defined as relapsed disease &gt; 2 years from initial treatment. LR remains a challenge both for optimal screening methods and treatment. We report the method of detection, treatments received, and outcomes in patients with LR GCT. Methods: The prospectively maintained Indiana University testicular cancer database was queried identifying 2712 pts with GCT treated at Indiana University from January 2000 to January 2019. Method of detection of LR was recorded along with site, treatment received, chemo-naive vs chemo-exposed LR, and survival outcomes. Results: 90 pts with LR were identified. Median age at LR was 35.2 yr (range, 19.2-56.8). Primary tumor site was testis in 88 (98%), retroperitoneum in 1 (1%), and mediastinum in 1 (1%). Chemo-exposed accounted for 42 (47%) and chemo-naïve for 48 (53%) of cases. Table compares clinical characteristics and survival outcomes of chemo-exposed vs. chemo-naïve late relapse. 62% of chemo-exposed LR were diagnosed with elevated AFP. For the 42 chemo-exposed LR pts, 2-yr PFS based on treatment: surgery vs. chemo vs surgery+chemo was 48% vs 10% vs 45% (p = 0.105). For the 48 chemo-naïve LR pts, 2-yr PFS based on treatment: surgery vs. chemo vs. surgery+chemo was 100% vs 74% vs 37% (p = 0.004). Next generation sequencing was available for 9 patients. No actionable findings were found. Tumor mutational burden was low in all patients where genomic testing was available. Conclusions: Most pts with chemo-exposed LR will be diagnosed with an elevated AFP. GCT pts require lifetime follow-up with annual physical exam and tumor markers. Surgical resection, when feasible, remains our preferred treatment for chemo-exposed LR as chemotherapy alone offers only brief responses. Pts with chemo-naïve LR have more chemo-sensitive biology.[Table: see text]