tbuckley/cabot-search huggingface dataset:
Interleukin-1-beta concentration and neutrophil-lymphocyte ratio as possible predicting biomarkers of response to therapy with checkpoint inhibitors.
Authors: Rashida Orlova, Natalia V. Zhukova, Anna Malkova, Ekaterina Kaledina, Anna Gubal, Vladimir Sharoyko
Journal: Journal of Clinical Oncology (2021)

3024 Background: One of the discussed predictive markers of the immune therapy efficacy is the index of neutrophils to lymphocytes ratio in peripheral blood (NLr), which reflects the activity of adaptive immunity and correlates with the level of tumor-infiltrating lymphocytes (TILs). High NLr and low TILs are associated with disease progression. Interleukin-1-beta (IL-1β) is one of the main cytokines produced by the tumor microenvironment (TMO). Overexpression of the cytokine leads to a local immunosuppression. For some tumors, elevated serum IL-1β levels have been associated with a poor prognosis. The aim of this work is to analyze the serum IL-1β level as a marker of TMO activity and the NLr as a marker of adaptive immunity activity in relation to the response to therapy with checkpoint inhibitors in patients with various solid tumors. Methods: The study involved 63 patients with various solid tumors who were treated at the City Oncological Dispensary and were prescribed checkpoint inhibitors (nivolumab (n = 33), pembrolizumab (n = 23), ipilimumab + nivolumab (n = 7)). The determination of the level of IL-1β was performed using the ELISA method ("Interleukin-1-beta, ELISA-best", Novosibirsk), a clinical blood test was performed in a dispensary. The response to treatment was assessed 3-6 months after the start of therapy. Statistical analysis was carried out in GraphPad Prism. Results: Among the examined patients 49.21% (31/63) achieved partial regression or stabilization of the process (group I), and 50.79% (32/63) progressed (group II). The mean concentration of IL-1β before treatment in group I was 2.21±0.3 pg/ml, in group II - 0.98±0.2 pg/ml. NLr was increased in 7 patients from group I and in 9 patients from group II, with the mean index level being 2.9±0.39 and 3.2±0.5, respectively. There was no statistically significant difference in the concentration of IL-1β and the NLr between the studied groups. In group II, the number of patients undergoing systemic anticancer therapy before immune therapy (n = 18) was statistically significantly higher than in group I (n = 8), p = 0.033. There was no statistically significant difference in IL-1β concentration and NLr relative to previous treatment. Conclusions: Our study showed that the level of IL-1β corresponds to that of healthy donors and its isolated determination has no prognostic value. The NLr in most patients from the progression group was higher than normal, in contrast to group I, which is confirmed in the literature. The presence of previous systemic anticancer therapy was found to be associated with disease progression. The described feature can be explained by the fact that patients who received therapy before, already have a longer period of illness, a more severe clinical condition. The presence of systemic anticancer therapy does not affect the level of IL-1β and NLr.
Efficacy of 5-Azacitidine on IDH1/2 Acute Myeloid Leukemia/Myelodysplastic Syndromes and Correlation with 2-Hydroxyglutarate Production
Authors: Christophe Willekens, Veronique Saada, Sophie Broutin, Julia Delahousse, Aline Renneville, Cynthia Petrovanu, Christophe Marzac, Jean-Baptiste Micol, Éric Solary, Florence Pasquier, Julien Lazarovici, Vincent Ribrag, Claude Preudhomme, Cyril Quivoron, Virginie Penard-Lacronique, Angelo Paci, Stephane de Botton
Journal: Blood (2017)
Racial and regional differences in incidence of oropharyngeal cancer in the United States during 2001 to 2017.
Authors: Fangjian Guo, Mihyun Chang, Abbey Berenson
Journal: Journal of Clinical Oncology (2021)

6041 Background: The incidence of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) has been reported to be increasing among both middle-aged and elderly adults in the United States. This study was to assess racial and regional differences in the incidence of OPSCC among adults in the US. Methods: We included 271,037 adult patients ≥ 20 years old diagnosed with potentially HPV-related OPSCC from the US Cancer Statistics 2001–2017 database which essentially covered the entire US population. Incidence of OPSCC was age- adjusted to the US standard population. Annual percentage change (APC) in the incidence was assessed across races/ethnicities and regions of residence. Results: Among these adults with potentially HPV-related OPSCC from 2001-2017, 5.3% were Hispanics, 83.0% were non-Hispanic Whites, and 9.2% were non-Hispanic Blacks, and 79.1% were male. Incidence of OPSCC increased from 3.9 per 100,000 in 2001 to 4.0 per 100,000 in 2017 (APC 0.43, 95% confidence interval (CI) 0.01, 0.85) in Hispanics, increased from 5.3 per 100,000 in 2001 to 8.6 per 100,000 in 2017 (APC 2.97, 95% confidence interval (CI) 2.71, 3.24) in non-Hispanic Whites, and decreased from 6.3 per 100,000 in 2001 to 5.1 per 100,000 in 2017 (APC -1.27, 95% confidence interval (CI) -1.56, -0.99) in non-Hispanic Blacks. The incidence increased from 5.8 per 100,000 in 2001 to 7.8 per 100,000 in 2017 (APC 1.94, 95% confidence interval (CI) 1.67, 2.21) in the South, increased from 5.0 per 100,000 in 2001 to 7.1 per 100,000 in 2017 (APC 2.13, 95% confidence interval (CI) 1.92, 2.34) in the Northeast, increased from 4.9 per 100,000 in 2001 to 6.3 per 100,000 in 2017 (APC 1.85, 95% confidence interval (CI) 1.53, 2.17) in the West, and increased from 4.9 per 100,000 in 2001 to 7.7 per 100,000 in 2017 (APC 2.79, 95% confidence interval (CI) -2.52, 3.07) in the Midwest. The incidence decreased from 0.9 per 100,000 in 2001 to 0.8 per 100,000 in 2017 (APC -0.81, 95% confidence interval (CI) -1.41, -0.20) among adults 20-44 years old, increased from 9.0 per 100,000 in 2001 to 12.7 per 100,000 in 2017 (APC 2.01, 95% confidence interval (CI) 1.66, 2.36) among adults 45-64 years old, and increased from 10.9 per 100,000 in 2001 to 16.7 per 100,000 in 2017 (APC 2.96, 95% confidence interval (CI) 2.75, 3.16) among adults 65+ years old. Conclusions: OPSCC incidence increased across racial/ethnic groups, regions, and age groups from 2001 to 2017, except that the incidence decreased among non-Hispanic Blacks and young people. Underlying causes for the decreasing trend in the incidence of OPSCC among certain groups need further investigation.
Real-life data of niraparib maintenance treatment in patients with recurrent platinum-sensitive ovarian cancer.
Authors: Bente Vilming, Jørgen Fallås-Dahl, Anne-Gry Bentzen, Vibeke Anett Ingebrigtsen, Elisabeth Berge Nilsen, Ingvild Vistad, Anne Dørum, Olesya Solheim, Line Bjørge, Guro Aune, Kristina Lindemann
Journal: Journal of Clinical Oncology (2021)

5560 Background: PARP (poly adenosine diphosphate [ADP]–ribose polymerase) inhibitors are the new standard for maintenance treatment in platinum sensitive recurrent ovarian cancer (PSROC), independent of germline (g-BRCA) or somatic BRCA mutation status. Real-life data after the introduction of new anti-neoplastic agents are needed to evaluate whether the benefit observed in phase III trials can be translated into clinical practice. The aim of this study was to provide real-life data on efficacy and safety of niraparib in non-gBRCA PSROC. Methods: This retrospective multi-center cohort study included patients with PSROC who were enrolled in a national individual patient access program in Norway. Efficacy and safety data were collected from the patients´ electronic medical records. The primary outcome was time from start of niraparib treatment to first subsequent treatment (TFST). Secondary endpoints included prevalence of dose interruption and -reduction, as well as adverse events. Results: The study included 106 patients with median age of 64 years (range 38-81). After median follow up of 15.3 months (95% CI 12.1-18.5), 71 patients (67%) had progressed, 64 (60%) had started a new line of treatment, and 25 (24%) had died. 25 (24%) patients were still receiving niraparib. Median duration of niraparib treatment was 7.6 months (0.4 to 27.3 months). Median TFST was 11.7 months (95% CI 9.2 -14.2). Patients with elevated CA125 after chemotherapy prior to start of niraparib had shorter progression-free survival (PFS) compared to patients with complete serological response (6.5 months (95% CI 5.7 – 7.3) vs 12 months (95% CI 6.2 – 17.9, (p &lt; 0.001)). Grade 3-4 hematologic and non-hematologic events occurred in 25% and 17% of the patients, respectively. The most common grade 3/4 hematologic events were anemia (15%), thrombocytopenia (11%) and neutropenia (8%). Adverse events led to dose interruption in 38% and dose reduction in 44% of the patients. Patients with individualized dosing based on baseline weight and platelet counts had fewer dose reductions (p &lt; 0.001) and -interruptions (p = 0.042) than patients whose dose was not adjusted to those baseline values. Conclusions: In a real-life setting, niraparib maintenance treatment in patients with non-gBRCA PSROC showed efficacy comparable with the published phase III data and an acceptable safety profile. Individualized dosing at start of treatment minimized adverse events. The prolonged PFS in patients with CA125 normalization after last chemotherapy, suggests that these patients in particular benefit from maintenance treatment but warrants confirmation in a larger sample.[Table: see text]
Postmarketing requirements for drugs approved by the Food and Drug Administration for the treatment of solid tumor cancers, 2010-2019.
Authors: Yolaine Jeune-Smith, Marjorie E. Zettler, Stephanie Fortier, Skyler Rupard, Ajeet Gajra, Bruce A. Feinberg
Journal: Journal of Clinical Oncology (2021)

e13597 Background: In recent years, efforts to improve the efficiency and speed of drug development and approval have driven a surge of Food and Drug Administration (FDA) approvals for cancer drugs. For many cancer therapies, the serious or life-threatening nature of the condition and unmet medical need confers eligibility for expedited programs. Many cancers are also rare diseases, and the increasing use of precision medicine principles to define cancer types further contributes to smaller trial sizes. With limited clinical evidence at the time of approval, cancer drugs may be subject to a greater burden of postmarketing requirements (PMRs). We analyzed PMRs for solid tumor therapies approved by the FDA over the past decade. Methods: The FDA’s novel drug approvals (2010-2019) were reviewed to identify drugs receiving primary approval for solid tumor indications. Approval letters were accessed via the Drugs@FDA database and analyzed for PMRs required under accelerated approval (AA), the Pediatric Research Equity Act (PREA) and the FDA Amendments Act of 2007 Section 505(o) (505(o)). Data are presented using descriptive statistics. Results: A total of 60 drugs received primary approval from the FDA for solid tumor indications between 2010 and 2019 (20 [33.3%] received AA, 33 [55.0%] received orphan designation, and 45 [75.0%] received Fast Track or Breakthrough Therapy designation). The proportion of drugs receiving AA doubled between the period 2010-2014 and 2015-2019 (Table). Of the 60 drugs approved, 52 (86.7%) received a total of 180 PMRs. All 20 drugs approved under AA received PMRs, with a total of 25 PMRs issued under AA. Data from new clinical trials were required for 22 (88.0%) of the 25 PMRs. No PMRs were issued under PREA. Additional safety data required under 505(o) comprised the largest proportion of PMRs; 155 total PMRs (86.1% of all PMRs) were issued for 45 (75.0%) of the drug approvals. Pharmacokinetic or other clinical safety data were required for 96 (61.9%) of the 155 PMRs. Conclusions: More than three-quarters of the cancer drugs approved for the treatment of solid tumors in the past 10 years were issued PMRs, with the majority requiring new safety data. The results of this study indicate that PMRs represent a critical mechanism by which FDA collects safety and efficacy for solid tumor therapies, and underscore the importance of PMR fulfillment. Post-marketing requirements (PMRs) for solid tumor drugs approved 2010-2019.[Table: see text]
A novel biosignature identifies DCIS patients with a poor biologic subtype with an unacceptably high rate of local recurrence after breast conserving surgery and radiotherapy.
Authors: Frank Vicini, Chirag Shah, Pat W. Whitworth, Steven C Shivers, Fredrik Warnberg, Bruce Mann, Troy Bremer
Journal: Journal of Clinical Oncology (2021)

513 Background: There is an unmet need to identify women diagnosed with DCIS who have a low recurrence risk and could omit radiotherapy (RT) after breast conserving surgery (BCS), or an elevated recurrence risk after treatment with BCS plus RT. DCISionRT and its response subtype (Rst) biosignature were evaluated in a contemporary cohort treated with BCS with or without RT to identify these risk groups. Methods: Pathology, clinical data, and FFPE tissue samples were evaluable for 485 women diagnosed with DCIS at centers in Sweden (1996-2004), the USA (1999-2008), and Australia (2006-2011). Patients were treated with BCS (negative margins) with or without whole breast RT. Ipsilateral breast tumor recurrence (IBTR) included DCIS or invasive breast cancer (IBC) that was local, regional, or metastatic. The patients were classified into Low and Elevated risk groups to assess IBTR and IBC rates. Patients in the Elevated risk group were categorized by two subtypes: a good response subtype (good Rst) or a poor response subtype (poor Rst) after BCS plus RT. Biosignatures were calculated using biomarkers (p16/INK4A, Ki-67, COX-2, PgR, HER2, FOXA1, SIAH2) assayed using IHC on FFPE tissue. Hazard ratios and 10-year risks were calculated using Cox proportional hazards (CPH) and Kaplan-Meier analyses. Results: In the DCISionRT Elevated risk group, RT was associated with significantly reduced recurrence rates, but only for those patients with a good Rst (Table, IBTR HR=0.18, p&lt;0.001, IBC HR=0.15, p=0.003, n=241). For Elevated risk group patients with a poor Rst, no benefit to RT was noted (Table). Additionally, irrespective of RT, patients with a poor Rst had 10-year IBTR/IBC rates of 25%/16%, which were much higher than good Rst rates of 6.6%/4.5% (IBE HR=3.6, p=0.02, IBC HR=4.4, p=0.04, n=190). For patients in the Low risk group, there was no significant difference in 10-year IBTR/IBC rates with and without RT (Table, IBTR p=0.4, IBC p=0.9, n=177). The distribution of clinicopathologic risk factors (age &lt;50 years, grade 3, size &gt;2.5 cm) did not identify poor vs. good response subtypes, and multivariable analysis (n=485) indicated these traditional clinicopathologic factors and endocrine therapy were not significantly associated with IBTR (p≥0.22) or IBC (p≥0.34). Conclusions: Biosignatures identified a Low risk patient group with low 10-year recurrence rates with or without RT who may be candidates for omitting adjuvant RT. Biosignatures also identified an Elevated risk group receiving BCS plus RT with a poor response subtype that had unacceptably high recurrence rates, warranting potential intensified or alternate therapy.[Table: see text]
Pseudoprogression and cancer immunotherapy: A seven year retrospective study of rate, temporal course, and predictive markers in an Irish tertiary referral center.
Authors: Kate McKendry, Fiona Desmond, Cian Ward, Austin G Duffy
Journal: Journal of Clinical Oncology (2021)

2651 Background: Immunotherapy is a relatively new treatment strategy which has achieved unprecedented clinical efficacy in many advanced malignancies. However, the pattern of tumour response to immunotherapy is distinct from other therapies and poses major challenges to clinicians. One such challenge is pseudoprogression. The aim of this study was to assess the current management of patients on immunotherapy with radiological evidence of disease progression at first restaging imaging in an Irish cancer centre, and to determine the rate, time course, and predictive markers of pseudoprogression in those patients treated beyond progression (TBP). Methods: Patients treated with immunotherapy for metastatic malignancy in MMUH between March 2013 and September 2020 were retrospectively drawn. Inclusion required follow-up restaging imaging every 4-12 weeks for the duration of treatment. Patterns of response during immunotherapy were established from radiology reports and categorized as stable (SD), response (R), mixed disease (MD), or progressive disease (PD). Pseudoprogression was defined as progression/ mixed disease at first restaging compared to baseline followed by subsequent response/stable disease. Results: The cohort of 228 patients was comprised of 80 NSCLC, 74 melanoma, 25 RCC, 19 gynaecological, 14 gastrointestinal, 6 breast, 1 ESSCLC, and 9 other cancer patients. Median age was 61.16 (IQR 49.47-69.44). Therapeutic agents were anti-PD1 alone (176) or in combination with targeted therapy (6) or CTLA4 (13), CTLA4 alone (15), and anti-PD-L1 alone (13) or in combination with chemotherapy (5). At first restaging, the number (%) classified as SD, R, MD, and PD, respectively, was 29 (12.8), 62 (27.2), 16 (7), and 76 (33.3). Treatment was stopped prior to restaging in 44 (19.3) cases. Of the 92 patients with mixed/ progressive disease, 41 were TBP and 51 were not treated beyond progression (NTBP). Evidence of radiological progression and worsening performance status (PS) were the most common reasons given by clinicians for NTBP. Of those TBP, 20 had subsequent response/stable disease, occurring at a median of 105.50 (range 58.0-420) days after the initial restaging scan and giving an overall pseudoprogression rate of 8.8%. At one year, 100% of the pseudoprogression group was alive. The neutrophil-lymphocyte ratio (NLR) was significantly lower in the pseudoprogression group compared to those with true progression (p = 0.006). There was no significant difference in performance status between the two groups. Conclusions: Pseudoprogression on cancer immunotherapy is real but uncommon, with an overall incidence of 8.8%. It can occur any time up to 420 days after initial progression and indicates a high likelihood of &gt; 1 year survival. A low NLR may be a useful predictor of pseudoprogression but a technological solution is likely needed.
An oncopalliative expertise unit in a French comprehensive cancer center: Experience at one year.
Authors: Christine Mateus, Laurence Vigouret-Viant, Sabine Voisin, Sophie Laurent, Perrine Renard, Anda Sampetrean, Elena Pavliuc, Florian Scotte, Sarah Dauchy
Journal: Journal of Clinical Oncology (2021)

e24077 Background: Anticipation of palliative care improves advanced cancer patients quality of life and may increase survival. It has also been associated with health costs reduction. However it is made difficult by societal taboos and reluctance of patients and caregivers to talk about therapeutic limitations and end of life. Methods: In a large French Comprehensive Cancer Center (CCC), the causes for both emergency consultations and medical hospitalizations have been analyzed, showing that repeated hospitalizations are more frequent when the level of care complexity increases and when the therapeutic project is unclear. Considering the European and international experiences of acute palliative care unit (APCU), we decided to create an APCU with reinforced onco-palliative expertise. This Onco-Palliative Expertise Unit (OPEU) main objective, besides treating refractory symptoms is to allow oncologists, palliative care specialists, pts and relatives to discuss together in order to redefine the therapeutic project. Results: One year after opening, this 10-bed unit has received 251 patients in 314 stays. 53% came directly from the home, 46% were already being followed by our palliative care team. After an average length of stay of 11.6 days, discharge was distributed between return home (41%), a palliative care unit (26%), death (22%) and other oncology units, or other hospitals (11%). At the opening, refractory symptoms were the most frequent reason for hospitalization (67% of stays). For the first 6 months period to the second one, discussing the therapeutic project increased from 23% to 34% of the hospitalization causes in the OPEU, showing the appropriation of this unit by the oncologists. A discussion about the project was carried out for almost all stays. On admission, specific cancer treatment was ongoing for 56% of stays. After assessment and multidisciplinary discussion, 49% of them decided to stop chemotherapy. Conversely, the start or resumption of treatment was recommended for 9% of stays without specific treatment on admission. The OPEU is a decompression chamber in the pt care pathway, which allows a multidisciplinary analysis of the pt’s condition on a single unit and leads to a quick and more appropriate therapeutic decision. Of the 251 pts hospitalized, only 19% were readmitted to hospital during the same one-year period, mainly for refractory symptoms. Conclusions: The creation of an OPEU in a CCC allows getting around the taboo of palliative care. It supports the dialogue between the oncologist and the pt, allows the pt to make the therapeutic project evolve toward a life project, avoiding costly unreasonable obstinacy.
Supportive care services (SCS) during curative-intent treatment with chemoradiation for patients with locally advanced head and neck cancer (HNC).
Authors: Ethan Harris, Alec Kacew, Siva Sreedhar, Ardaman Shergill
Journal: Journal of Clinical Oncology (2021)

e18041 Background: SCS assist in managing symptoms and outcomes for patients in palliative care settings. But impact of services in curative intent settings is not well defined. Here we evaluate this for head and neck cancer patients. Methods: Following IRB approval, we retrospectively reviewed charts of patients with HNC treated from 2014-2017 at the University of Illinois Hospital. Of 260 patient charts reviewed, 67 patients fit the study criteria, which included completing treatment with curative intent at University of Illinois Hospitals, not living at a skilled nursing facility, and follow-up of at least 3 months. Demographic data and treatment course data were collected. SCS included opioid use, tracheostomy use, G-tube use, prophylaxis for mucositis, speech and swallow f/u, nutritionist visits, social worker visits, and anti-emetic prophylaxis. Outcomes included number of hydration visits, number of ER visits, and number of days in the hospital. We tested the significance of correlations between continuous variables using Pearson correlation and the significance of difference in a continuous variable between two groups using the Wilcoxon ranked sum test. We used Cox proportional hazards model for analyses of overall survival (OS). Analyses were univariable. Results: 20 patients had oropharyngeal cancer. 47 had non-oropharyngeal disease. 57 patients received cisplatin and 10 patients received cetuximab, concurrently with radiation therapy. Median weight loss was 6.0kg during treatment. Highest potency opioid at end of treatment was not associated with outcomes. Among the full cohort, having a G-tube was associated with increased number of ER visits (median 1.5 vs. 0.0, p &lt; 0.01), hospitalizations (median 2.0 vs. 0.0, p &lt; 0.01), and number of days in the hospital (median 7.0 vs. 0.0, p &lt; 0.01). Increased hydration appointments, meanwhile, did not predict outcomes. In subgroup analysis of patients who received G-tubes, ER visits before or after G-tube placement did not predict OS (HR 0.64, p = 0.56 for ER visits before G-tube placement, HR 1.06, p = 0.75 for ER visits after G-tube placement). Number of hydration visits after starting treatment for cetuximab vs cisplatin was significant (median 8 for cisplatin and 2 for cetuximab, p = 0.02). Conclusions: G-tube placement, even after placement, was associated with medical care needs during treatment, suggesting an unmet need for this patient population. Further studies are needed to determine how to best provide support for this vulnerable patient population.