tbuckley/cabot-search huggingface dataset:
Effect of neoadjuvant systemic therapy given during window trials on quality metrics in resectable head and neck squamous cell carcinoma.
Authors: Marco Antonio Mascarella, Varun Vendra, Mark Kubik, Shaum Sridharan, Seungwon Kim, Robert L. Ferris, Moon Jung Fenton, James Ohr, Dan Paul Zandberg, Umamaheswar Duvvuri
Journal: Journal of Clinical Oncology (2021)

6033 Background: Quality oncologic care, including negative surgical margin status, adequate lymph node yield and prompt initiation of adjuvant treatment, impacts disease control and overall survival in patients with mucosal head and neck squamous cell carcinoma (HNSCC). The aim of this study was to ascertain the effect of neoadjuvant systemic therapy given during window trials on oncologic quality metrics in patients with delayed definitive surgery for a HNSCC. Methods: Treatment-naïve patients with HNSCC participating in one of two window of opportunity clinical trials at UPMC from 2009-2019 were included. Neoadjuvant regimens consisted of one dose of cetuximab (n = 33) or anti-ErbB3 antibody (n = 9) within 28 days of surgery. Sociodemographic, clinical and tumor staging were recorded. The primary outcome was overall oncologic quality, as defined as a composite measure of negative margin status, adequate lymph node yield, completion of adjuvant therapy (if indicated) and time to initiation of adjuvant therapy within 6 weeks of surgery. Secondary outcomes were difference in clinical and pathologic stages and overall survival (OS). Results: A total of 42 patients with a mean age of 57.1 (±10.2) years and median follow-up of 58 months were analyzed. 29 patients had clinical stage IVA disease with 43% (18/42) oral cavity, 36% (15/42) larynx/hypopharynx and 21% (9/42) oropharynx primaries. All patients underwent surgery following neoadjuvant systemic therapy. In 30 patients (71%), all oncologic quality markers were achieved. Pathological downstaging occurred in 21% (9/42) of patients with 4 patients no longer meeting criteria for adjuvant treatment and were observed. 3 patients showed pathological upstaging. The 3-year OS were 76% (95% CI of 63.6-88.4), respectively. Patients with a pathologic downstage migration (64.9%, 95% CI of 49.9-79.8) had higher 5-year OS compared to those without (57.8%, 95% CI of 40.1-76.4, P = 0.046). Conclusions: Most patients receiving neoadjuvant systemic therapy on window trials prior to surgery met all oncologic quality markers. Importantly, even with brief window trial therapy pathologic downstaging was achieved and associated with significantly better overall survival.
Hot clear cell renal cell carcinoma immune status: Illusion or reality?
Authors: Xingang Bi, Yi Lu, Xinyu Bi, Zhiwen Luo
Journal: Journal of Clinical Oncology (2021)

e16575 Background: High tumor mutation burden (TMB) and increased CD8+ T cells infiltration are associated with positive ICIs response in many solid cancers. But non-responsive clear cell renal cell carcinoma (ccRCC) features modest TMB, high CD8+ T-cell infiltration but poor survival. Costimulatory molecules confer immune cell activation within the immune response. Therefore, we aimed to investigate ccRCC’s unique immune environment related prognosis and ICIs’ sensitivity from the aspect of co-stimulation alteration. Methods: We analyzed the combined ccRCC cohort of 844 patients’ RNA sequencing data, from two sources: One ccRCC group (533 patients) was from The Cancer Genome Atlas KIRC (TCGA-KIRC), and the validation group (311 patients) was from an ICIs treated clinical trial. Univariate, LASSO, and multivariate Cox regression analyses were used to identify overall survival-related costimulatory genes, which were used to build an immune prognostic model (IPM) stratifying survival risk level in ccRCC. Comprehensive bioinformatics discovered the relationship between immune status, ICIs’ sensitivity with IPM’ prognosis risk. Results: The survival related co-stimulatory genes were identified in 533 ccRCC patients to construct an immune prognostic model (IPM) to differentiate patients with a low or high risk of poor survival (AUC = 0.75). Functional enrichment analysis showed T cell homeostasis represented the major function alteration related to IPM risk score ( P&lt; 0.05). ICIs clinical trial cohort validated the IPM’s moderate prediction performance for the ICIs response ( P= 0.028), for IPM-high risk patients are more likely to be resistant to ICIs. The high-risk group had higher CD8 + T cell infiltration, higher TMB, and higher cytolytic activity, while such a hot immune status was an illusion concealing the T cells homeostasis alteration with the increased proportion of dysfunctional CD8+ and CD4+ T cells, immunosuppressive cells (i.e., iT-regs, nT-regs, and CAFs) in IPM-high risk, this kind of refractory ccRCC subtype. Conclusions: Baseline CD8 + T cell infiltration, TMB, and cytolytic activity could not predict response to ICI in the ccRCCs, and hot tumor immune status represented by CD8+T cells in resistant ccRCC is an illusion concealing T cells homeostasis alteration. T cells homeostasis could provide critical insights into immunogenomic mechanisms contributing to the immunotherapy sensitivity in ccRCC. Our five-gene based IPM tested easily by PCR, was clinically accessible, cheap and useful for indicating refractory ccRCCs to undergo ICIs.
Quality indicators for glioblastoma treatment: An audit from a tertiary care cancer center in India.
Authors: Love Goyal, Santam Chakraborty, Saheli Saha, Paromita Roy, Lateef Zameer, Deepak Mishra, Mayur Parihar, Aditi Chandra, Moses Arunsingh, Sanjoy Chatterjee, Indranil Mallick, Tapesh Bhattacharyya, Bivas Biswas, Rimpa Basu Achari
Journal: Journal of Clinical Oncology (2021)

e18659 Background: Surgery followed by chemoradiotherapy with temozolomide (TMZ) is the standard of care for glioblastoma. There are limited reports of quality metrics in glioblastoma. We present an audit of adherence to selected quality indicators proposed in the PRIME Quality Improvement study. Methods: Retrospective audit of quality indices for glioblastoma patients treated between 2017 - 2020. Patients were treated within a standard protocol of postsurgical integrated molecular diagnosis, radiotherapy with concurrent and adjuvant TMZ. Multiparametric MRI at predefined time-points of pre- and post radiation, interim and end of adjuvant TMZ guided management. Demographic, clinical, pathological, imaging, therapy and outcomes data was abstracted. Numbers with proportions for indices were calculated. Survival was estimated using the Kaplan Meier method. Results: Ninety-four glioblastoma patients were treated from 2017 to 2020. Quality metrics are reported (table). Patients in whom adjuvant TMZ could not be started or continued for 6 cycles had progressive disease and salvage chemotherapy was initiated. The 12 month overall and progression free survival was 74.6% (95% CI : 65.4% - 85.1%) and 43.6% (95% CI : 33.8% - 56.3%) respectively. Conclusions: Our patients met quality indices in most domains; outcomes are comparable with global results. These metrics will be periodically evaluated and updated to include newer standards to assess our continued service appropriateness.[Table: see text]
Brain correlates of chemotherapy-induced peripheral neuropathy (CIPN) during somatosensory and interoceptive attention: A functional MRI (fMRI) study.
Authors: Ian Kleckner, Amber Kleckner, Elizabeth Belcher, Huiwen Xu, Po-Ju Lin, Richard Francis Dunne, Michelle Christine Janelsins, Shelli R. Kesler, Karen Michelle Mustian
Journal: Journal of Clinical Oncology (2021)

e24095 Background: Over half of patients receiving neurotoxic taxane, platinum, or bortezomib chemotherapy experience CIPN—a dose-limiting toxicity involving numbness and pain in the extremities. There are limited biomarkers and treatments for CIPN partly due to lack of knowledge of its pathophysiology. Here, we studied whether CIPN involves changes in the brain’s sensory processing circuitry to inform novel brain-based biomarkers and brain-based treatments for CIPN. Methods: Eleven patients scheduled to receive taxane, platinum, or bortezomib rated CIPN severity (CIPN-20) and completed an fMRI scan before starting neurotoxic chemotherapy and/or 12 weeks later. The 7-min fMRI task involved alternating 20-sec trials of distinct attentional focus: (1) their left fingertips (somatosensory attention), (2) their heart (interoceptive attention), and (3) a flashing word “target” (visual attention; the reference condition). We found an activation cluster in primary somatosensory cortex (S1) comparing somatosensory vs. visual attention and another cluster in primary interoceptive cortex (mid/posterior insula) comparing interoceptive vs. visual attention. We tested for associations between CIPN severity and task-based activations in S1 and the insula. Because this is a pilot study, we present effect sizes (ESs) using Cohen’s d and Pearson’s r, not p-values. Results: The 11 patients were 63±12 years old, 54% women, and 54% had breast cancer with high-quality fMRI data (16 scans; 8 pre-chemotherapy). As expected, somatosensory attention increased activation in S1 compared to visual attention (ES = 1.46), and interoceptive attention increased activation in the insula compared to visual attention (ES = 0.94). Patients with worse CIPN had smaller increases in S1 activation during somatosensory vs. visual attention (ES = 0.38), suggesting reduced S1 activation during somatosensory attention (i.e., failure to activate S1) and/or increased S1 activation during visual attention (i.e., S1 chronically activated). Similarly, patients with worse CIPN had smaller increases in insula activation during interoceptive vs. visual attention (ES = 0.57). Individual differences in S1 or insula activity were not significantly explained by age, anxiety, or problems remembering (all ESs &lt; 0.12). Conclusions: CIPN severity was associated with changes in brain activity during a simple attentional task during fMRI scanning, implicating the brain’s somatosensory and interoceptive processing in CIPN. Future work should test for replication and develop biomarkers and treatments for CIPN that target somatosensory and interoceptive processing, perhaps using this attention task. NCT03021174. Funding: NIH R25CA102618, UG1CA189961, K07CA221931. Clinical trial information: NCT03021174.
B-CELL LYMPHOMA CELLS OVEREXPRESSING BMI-1 ARE CORRELATED WITH DRUG RESISTANCE THROUGH ENHANCED EXPRESSION OF SURVIVIN AND ARE MORE EFFECTIVELY ELIMINATED BY T CELLS WITH CHIMERIC RECEPTOR AGAINST CD38 THAN CD19
Authors: Kimura A, Hoshi M, Takihara Y, Ohtsubo M, Bhattacharyya J, Mihara K
Journal: Annals of Oncology (2011)
Improved survival in multiple myeloma during the 2005–2009 and 2010–2014 periods
Authors: Jill Corre, Aurore Perrot, Cyrille Hulin, Denis Caillot, Anne-Marie Stoppa, Thierry Facon, Xavier Leleu, Mamoun Dib, Lionel Karlin, Philippe Moreau, Mohamad Mohty, Clara Mariette, Jean Fontan, Jean-Pierre Marolleau, Hélène Demarquette, Borane Slama, Laurent Voillat, Margaret Macro, Frédérique Orsini-Piocelle, Sabine Brechignac, Philippe Rey, Philippe Collet, Mourad Tiab, Karim Belhadj, François Lifermann, Lauriane Clement-Filliatre, Claudine Sohn, Valentine Richez, Hervé Avet-loiseau
Journal: Leukemia (2021)
Association of C-reactive protein (CRP) with efficacy of avelumab + axitinib (A + Ax) in advanced renal cell carcinoma (aRCC): Long-term follow-up results from JAVELIN Renal 101.
Authors: Yoshihiko Tomita, James Larkin, Balaji Venugopal, John B. A. G. Haanen, Hiro-Omi Kanayama, Masatoshi Eto, Marc-Oliver Grimm, Yosuke Fujii, Yoshiko Umeyama, Mariangela Mariani, Alessandra Di Pietro, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2021)

4548 Background: CRP is an important prognostic and predictive factor in patients with aRCC receiving various therapies, such as cytokines and tyrosine kinase inhibitors. In this extended follow-up to the phase 3 JAVELIN Renal 101 trial (NCT02684006), we report the association of CRP levels at baseline (BL) and early after treatment with the efficacy of A + Ax or sunitinib (S). Methods: CRP levels were assessed at screening and day 1 of each 6-week cycle. Patients were categorized into CRP normal (BL CRP &lt; 10 mg/L), normalized (BL CRP ≥10 mg/L and ≥1 CRP value decreased to &lt; 10 mg/L during 6 weeks of treatment), and non-normalized (CRP ≥10 mg/L at BL and during 6 weeks of treatment) groups. Multivariate analysis of BL characteristics, including CRP for efficacy, was also conducted. Progression-free survival (PFS) and best overall response per independent central review (RECIST 1.1) from the second interim analysis (IA2) of overall survival (OS) and OS from the third interim analysis (IA3) were assessed. Results: Minimum duration of follow-up for IA2 and IA3 were 13 and 28 months, respectively. The table shows objective response rate (ORR), PFS, and OS by CRP group. Efficacy outcomes in the normal and normalized groups were favorable compared with the non-normalized group with both A + Ax and S. In the A + Ax arm, the complete response rate was 11.8% (normalized group), 3.8% (normal group), and 0.9% (non-normalized group). With A + Ax, the PFS in the normalized group was longer than in the normal group, but this was not observed with S. In each CRP group, all efficacy outcomes were favorable with A + Ax vs S. In the multivariate analysis, normalized or non-normalized CRP was an independent predictive factor of ORR or OS with A + Ax. Conclusions: Normal and normalized CRP levels were associated with improved A + Ax efficacy. A + Ax demonstrated favorable efficacy across CRP groups. OS in this study was immature; follow-up for the final analysis is ongoing. Further research in defining predictive value of CRP is warranted. Clinical trial information: NCT02684006. [Table: see text]
Young-onset colorectal: Emotional and psychosocial effects on patients, survivors, and caregivers.
Authors: Laura Diane Porter, Ronit Yarden, Kim Lynn Newcomer
Journal: Journal of Clinical Oncology (2021)

3592 Background: Colorectal cancer is the third-most commonly diagnosed cancer and the second-leading cause of cancer death in men and women combined in the United States. Young-onset colorectal cancer refers to individuals diagnosed under the age of 50. In recent years, the incidence has increased by 2.2% annually in individuals younger than 50 years, and 1% in individuals 50-64, in contrast to a 3.3% decrease in adults 65 years and older. The Colorectal Cancer Alliance launched the Never Too Young Survey and the Caregiver Survey to assess and better understand the unmet needs of the young-onset population and their caregivers. Methods: A cross-sectional study, conducted in the form of an online survey, was launched to better understand the experiences around YO-CRC patients and caregivers. YO-CRC patients and survivors (N = 885) and caregivers (N = 204) completed an online questionnaire that was based on established instruments including PROMIS, EORTC-QOL-30, and EORTC-CR-29. The final survey instrument and study plan were reviewed and approved by the Aspire Inc. Institutional Review Board. Results: Nearly 75% of patients/survivors shared that they have been concerned about their mental health, and 64% responded that they have needed help for their depression. Further, 67% of caregivers surveyed responded that they were also concerned about their mental health, and 68% responded that they needed help with their depression. Seventy-one percent of caregivers often felt sadness, and 30% indicated that they had lost hope. Emotional exhaustion was reported by 77% of caregivers, whether they were providing round-the-clock care or caregiving from a distance. The effect was more pronounced in the patient/survivor cohort, with 95% indicating that emotional exhaustion impacted their lives. As a result, 71% of caregivers and 29% of patients/survivors indicated that they had withdrawn from other people. These results indicate the emotional toll that colorectal cancer has on patients/survivors and caregivers and their need for further resources. Conclusions: The Colorectal Cancer Alliance is committed to meeting these needs and providing resources that support patients, survivors and caregivers. Information and services may assist the caregiver in helping the patient make decisions, including shifting roles and routines in response to changing demands of YO-CRC. Further studies should investigate psychological well-being and support strategies.
Development and molecular characterization of a human ovarian cancer cell line resistant to 2-Methoxyestradiol (1A9-2ME2R)
Authors: Daniel Escuin, Yuefang Wang, Theresa Lavallee, James H. Nettles, James P. Snyder, Paraskevi Giannakakou
Journal: Cancer Research (2005)

5092  We have recently identified a mechanistic link between disruption of the microtubule cytoskeleton and inhibition of tumor angiogenesis via the hypoxia inducible factor-1 (HIF-1) pathway. HIF-1 is a pro-angiogenic transcription factor induced primarily by tumor hypoxia, which is critically involved in tumor progression, metastasis and overall survival. We have shown that disruption of interphase microtubules by the microtubule-destabilizing drug 2ME2 impairs tumor angiogenesis by inhibiting HIF-1 levels and transcriptional activity. In order to get more insight on the molecular mechanism of HIF-1α downregulation by 2ME2, we have established a 2ME2 resistant cancer cell line (1A9/2ME2-R), by culturing 1A9 human ovarian cancer cells in the presence of increasing 2ME2 concentrations. Preliminary molecular characterization of the 1A9/2ME2-R cells has identified an acquired β-tubulin point mutation at residue 236 (GTC to ATC) leading to a Val to Ile substitution. These resistant cells exhibited 25-fold resistance to 2ME2 compared with their parental 1A9 counterparts, while remaining sensitive to other microtubule-targeting agents, including paclitaxel, colchicine and vincristine. Further mechanistic studies revealed that 2ME2 was unable to significantly inhibit HIF-1α protein in the 1A9 2ME2-R cells, consistent with the lack of drug-induced tubulin depolymerization in these beta-tubulin mutant cells. This result is in sharp contrast with the ability of 2ME2 to both depolymerize microtubules and inhibit HIF-1α protein in the parental 1A9 cells harboring wild-type tubulin. Our previous observation that pharmacologic disruption of microtubules is required for the downstream HIF-1α inhibition is both extended and confirmed. Ongoing studies in our laboratory are utilizing the 1A9 2ME2-R cells and 2ME2 analogs (modified at positions 3 and 17) as tools to elucidate the mechanism of microtubule-dependent regulation of HIF-1α, and to dissect the structural elements of 2ME2 contributing to the drug’s antitumor and antiangiogenic activity.
The Importance of Considering Frailty in Research on Older Adults—Reply
Authors: Mary R. Rooney, Elizabeth Selvin
Journal: JAMA Internal Medicine (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Contextualizing a single-arm trial of ceralasertib (cer) plus paclitaxel with real-world data (RWD) in patients (pts) with advanced melanoma previously treated with anti-PD-(L)1(PDx) therapies.
Authors: Miao Jiang, Jeeyun Lee, Daniel Jackson, Simon Smith, Sajan Khosla, Bienvenu LoembE, Emma Dean, Claire Smith
Journal: Journal of Clinical Oncology (2021)

e21542 Background: Metastatic melanoma, especially in pts who do not respond to PDx therapy, is an area of high unmet need. Chemotherapy may be used but clinical efficacy is limited. A recent Phase I study (NCT02630199) showed that cer + paclitaxel had promising anti-tumor activity with durable responses in 34 melanoma pts after failing PDx therapy. Given the lack of published prospective clinical trial data in the post-PDx setting, RWD was used to contextualize the results of the trial. Methods: Adult pts (≥18 years) diagnosed with advanced melanoma between Jan2011-Jun2020, who received PDx therapy alone or in combination with anti-CTLA4, and also received chemotherapy immediately after the PDx line (chemo cohort) were selected from the nationwide US-based Flatiron Health EHR-derived de-identified database. A subgroup of pts who received taxane was also selected. Overall survival (OS) was assessed using Kaplan-Meier methods. Key covariates such as age, gender, LDH level, number of prior lines of therapy, presence of brain and liver metastases, and prior BRAF/MEK treatment, were adjusted using propensity score-based weighting approach. Cox regression models were used to obtain the effect estimates for OS comparing the trial arm against the RWD cohorts. Results: A cohort of 114 pts met the inclusion criteria, of which 69 received taxane. Compared with the trial arm, the RWD cohorts were older, contained more males, with higher proportions receiving prior BRAF/MEK inhibitors, with brain metastasis, and LDH≤ULN. Median OS was 7.4 months (mo) in the trial arm, compared to 5.6 (unadjusted) and 3.5 mo (adjusted) in the chemo cohort. Hazard ratio of 0.49 (95% CI: 0.29-0.83, trial vs. chemo) indicated significant benefits of the trial arm over the chemo cohort. Analyses using taxane subgroup showed similar findings. Conclusions: The RWD cohorts demonstrated poor outcomes for the pts receiving chemotherapy, in particular taxanes, confirming this is a population of unmet need. The results show the potential for improved outcomes using cer + paclitaxel in pts previously treated with PDx.[Table: see text]