tbuckley/cabot-search huggingface dataset:
A phase III multicenter randomized clinical trial to compare cisplatin plus fluorouracil with or without docetaxel as the first-line induction chemotherapy for locoregionally advanced nasopharyngeal carcinoma: Long-term outcomes update.
Authors: Wang Fang FangZheng
Journal: Journal of Clinical Oncology (2021)

6032 Background: A phase III multicenter prospective randomized controlled trial was conducted to compare cisplatin plus 5-fluorourcil with or without docetaxel as first-line induction chemotherapy in the patients with locoregionally advanced nasopharyngeal carcinoma (LANPC). Here, we report on the long-term outcomes and late toxicities of the trial (NCT01536223). Methods: Patients with newly diagnosed LANPC, stage III-IV disease, Karnofsky performance score≥70, without metastasis were eligible and randomly assigned 1:1 to TPF versus PF for three cycles. The primary end point was progression-free survival; local control, OS and advent events were important key secondary end points. The Kaplan-Meier method and the log-rank test were used to conduct and compare the survival curves in this study. Results: Two hundred ninety-nine patients were enrolled. 276 patients (138 TPF and 138 PF) were evaluable. Baseline characteristics were well-balanced between two groups, and the median age was 48 (range, 18-60 years). The ORR rates after induction chemotherapy and chemoradiotherapy were 90.6% and 9797.8% in TPF group and 87.0% (P &gt; 0.05) and 97.8% (P &gt; 0.05), respectively. The median follow-up was 99 months. For all patients, the 5- and 8-year OS and PFS were 76.9% and 74.9%, 72.3% and 69.1%, respectively. PF was associated with a similar PFS versus TPF ( 5-year PFS of 72.4% versus 73.2%, P =.747), and an equivalent OS at 5 years ( 79.2% and 79.1%, P = 0.519). Treatment-related grade 3 to 4 advent events were less frequent with PF compared with TPF. Conclusions: With prolonged follow-up, the survival outcomes in the PF group were not non-inferiority to those in the TPF group, but grade 3 to 4 advent events were less frequent. Clinical trial information: NCT01536223.
A phase II trial of chemotherapy plus pembrolizumab in patients with advanced NSCLC previously treated with a PD-1 or PD-L1 inhibitor: Big Ten Cancer Research Consortium BTCRC-LUN15-029.
Authors: Nikhil Shukla, Sandra K. Althouse, Susan Perkins, Muhammad Furqan, Ticiana Leal, Nasser H. Hanna, Greg Andrew Durm
Journal: Journal of Clinical Oncology (2021)

9073 Background: Chemoimmunotherapy with a platinum doublet plus a checkpoint inhibitor (CPI) is a standard of care for pts with advanced NSCLC. While some pts experience prolonged responses to initial CPI therapy, the majority of pts will eventually experience PD. It is unknown if continuing CPI treatment beyond progression has any advantages in this setting. We report the results of a phase 2 trial of chemotherapy plus pembrolizumab in pts with advanced NSCLC previously treated with a PD-1 or PD-L1 inhibitor. Methods: Pts experiencing PD after clinical benefit to CPI (PFS &gt; 3 months) were enrolled. Pts received pembrolizumab 200 mg q3wks plus next-line chemotherapy (gemcitabine 1000 mg/m 2 IV D1 and D8 q3wks, or docetaxel 60-75 mg/m 2 IV D1 q3wks, or pemetrexed 500 mg/m 2 IV D1 q3wks [non-squamous histology only]). The primary endpoint was PFS by RECIST 1.1. Key secondary endpoints included ORR, OS, and toxicity. The null hypothesis was median 3-month PFS with pembrolizumab plus next-line chemotherapy and the alternative hypothesis was median 6-month PFS with pembrolizumab plus chemotherapy. Results: 35 pts were enrolled. Median follow-up was 18.1 months and median age 63 (44-80). 51.4% male and 48.6% female. 82.9% were current or former smokers. Histology included 74.3% with adenocarcinoma, 20% with squamous cell carcinoma, 5.7% with NSCLC NOS. Treatment regimens included pembrolizumab/docetaxel (40%), pembrolizumab/gemcitabine (45.7%), or pembrolizumab/pemetrexed (14.3%). Median number of cycles of pembrolizumab was 6 (1-31). Median PFS using RECIST 1.1 and irRECIST was 5.2 months (95% CI 3.6-11.2, p &lt; 0.05) and 6.9 months (95% CI 3.8-12), respectively. Median OS was 26.8 months (95% CI 13.4-30.9). Best response using RECIST 1.1 was PR (23.5%) and SD (53%). 45.7% of pts experienced G3 or higher treatment-related AEs (TRAEs). Most common TRAEs were fatigue (60%), anemia (51.4%), and nausea (42.9%). There were no treatment related deaths. Conclusions: Pembrolizumab plus next-line chemotherapy in pts with advanced NSCLC who experienced PD after clinical benefit to CPI was associated with prolonged PFS compared with historical controls of single agent chemotherapy. Further investigations into which pts would benefit from continued CPI treatment after progression is warranted. Clinical trial information: NCT03083808.
Data on diabetes-specific distress are needed to improve the quality of diabetes care
Authors: Jane Speight, Norbert Hermanns, Dominic Ehrmann, Maria Teresa Anarte Ortiz, Koula Asimakopoulou, Arshiya Baig, Debbie Cooke, Sonya Deschênes, Maartje de Wit, Christopher Garrett, Eveline Goethals, Christel Hendrieckx, Elizabeth Holmes-Truscott, Richard IG Holt, Jörg W Huber, Khalida Ismail, Sanjay Kalra, Thomas Kubiak, Rossella Messina, Briana Mezuk, Giesje Nefs, Lisa Newson, Arie Nouwen, Frank Petrak, Frans Pouwer, Nouha Saleh-Stattin, Timothy C Skinner, Frank J Snoek, Jackie Sturt, Michael Vallis
Journal: The Lancet (2021)
Real-world efficacy and safety of lenvatinib-base therapy for patients with unresectable hepatocellular carcinoma in China: A multicenter retrospective analysis.
Authors: Qicong Mai, Song Chen, Feng Shi, Zhiqiang Mo, Jian He, Wenbo Guo, Xiaoming Chen
Journal: Journal of Clinical Oncology (2021)

e16192 Background: Lenvatinib has been approved as a first-line systemic for advanced hepatocellular carcinoma (HCC) after the randomized phase III REFLECT trial. The aim of this study was to assess the lenvatinib-base treatment patterns and safety in real-world clinical settings in China. Methods: In this multicenter retrospective study, A total of 278 patients with unresectable HCC were treated with lenvatinib-base treatment between October 2018 and November 2020 were analyzed. Therapeutic effect was determined using the RECIST 1.1 and mRECIST criteria. Progression free survival (PFS), overall survival (OS) and treatment-related adverse events (TRAE) were also evaluated. Results: Of 278 unresectable HCC patients (median age: 56.1±11.9 years), 220 (79.1%) had cirrhosis caused by HBV infection. 215 (77.3%) and 63 (22.7%) patients were classified as Child-pugh A and B class, respectively. 233 (83.8%) and 45 (16.2%) patients received lenvatinib in first-line and second-line systemic therapies, respectively. 223 (80.2%) patients were treated with lenvatinib plus arterially directed therapy (TACE or HAIC of FOLFOX) and 55 (19.8%) were treated with lenvatinib alone. The objective response rate were 34.9% (RECIST) and 47.5% (mRECIST), while the disease control rate were 75.5%. With a median follow-up period of 12.8 months, the median PFS and OS were 7.8 months (95% CI 7.1–8.4) and 17.2 months (95% CI 14.9–19.6), respectively. Results from the multivariate analysis showed that the significant independent favorable prognosis factors were tumor burden&lt; 50% (P=0.033), Child–Pugh A class (P&lt;0.01), AFP level &lt;200ng/mL (P=0.045), the combination with lenvatinib and arterially directed therapy (P&lt;0.01). TRAE occurred in 219 of 278 patients (78.8%), most common TRAE were hypertension (n=118; 42.4%) and hand-foot skin reaction (n=91; 32.7%). The most common grade 3–4 TARE were hypertension (n=23; 8.3%), decreased appetite (n=18; 6.5%), AST elevation (n=14; 5%), and diarrhea (n=14; 5%) across all study patients. Conclusions: In this multicenter real-world study, lenvatinib-base treatment could be accomplished with well tolerated and response for unresectable HCC patients. Combination with arterially directed therapy could likely improve the overall survival.
Decrease of oncological patients’ hospital visits during Covid-19 pandemic: The experience of a tertiary Romanian center.
Authors: Cristina Crisan, Calin Ioan Cainap, Andrada Larisa Deac, Andrei Dan Havasi, Ovidiu Balacescu, Loredana Balacescu, Ovidiu Vasile Bochis, Ioan-Cătălin Vlad, Simona Sorana Cainap
Journal: Journal of Clinical Oncology (2021)

e13607 Background: The outbreak of COVID-19 pandemic has changed the provision of medical services worldwide. Oncological patients continued receiving specialty treatments. We assess the impact of the pandemic on the oncological patients' visits to a tertiary cancer center. Methods: We analyzed registrations from the administrative data system of in and outpatients in all departments of the Cluj-Napoca Oncology Institute, during March-October 2020, compared to the same 7-month period of the previous year. Results: The decrease during March-October 2020 was of 40.2% for new referrals overall (with the most significant drop in April, of 80%), of 52.5% for medical oncology inpatients, 39% for pediatric oncology department inpatients, 69% for radiotherapy inpatients, 34.9% for surgical interventions and 31% decrease of issued pathology reports. The decrease was less important for outpatients: only 10% for medical oncology outpatient department, 33% for radiotherapy, and 27% for breast cancer unit outpatients. Imaging investigations were only slightly influenced by the pandemic (reduction of 5% for MRI scans, 19% for mammograms, whereas performed CT scans were even more after the outbreak of COVID-19). Conclusions: Our results show a decrease in the number of patients during the period after the outbreak of the COVID-19 pandemic, more for inpatients and less significant for outpatient departments, probably because of the internal circuits reorganization but also because of healthcare measures taken nationally and locally to limit the spread of the pandemic. Keywords: COVID-19, pandemic, oncology referrals, disruption.
ENO1 Promotes Lung Cancer Metastasis via HGFR and WNT Signaling–Driven Epithelial-to-Mesenchymal Transition
Authors: Hsin-Jung Li, Feng-Yi Ke, Chia-Ching Lin, Mei-Yi Lu, Yi-Huei Kuo, Yi-Ping Wang, Kang-Hao Liang, Shin-Chang Lin, Ya-Hsuan Chang, Hsuan-Yu Chen, Pan-Chyr Yang, Han-Chung Wu
Journal: Cancer Research (2021)

Abstract ENO1 (α-enolase) expression is significantly correlated with reduced survival and poor prognosis in many cancer types, including lung cancer. However, the function of ENO1 in carcinogenesis remains elusive. In this study, we found that high expression of ENO1 is present in metastatic lung cancer cell lines and malignant tumors and is associated with poor overall survival of patients with lung cancer. Knockdown of ENO1 decreased cancer cell proliferation and invasiveness, whereas overexpression of ENO1 enhanced these processes. Moreover, ENO1 expression promoted tumor growth in orthotopic models and enhanced lung tumor metastasis in tail-vein injection models. These effects were mediated by upregulation of mesenchymal markers N-cadherin and vimentin and the epithelial-to-mesenchymal transition regulator SLUG, along with concurrent downregulation of E-cadherin. Mechanistically, ENO1 interacted with hepatocyte growth factor receptor (HGFR) and activated HGFR and Wnt signaling via increased phosphorylation of HGFR and the Wnt coreceptor LRP5/6. Activation of these signaling axes decreased GSK3β activity via Src–PI3K–AKT signaling and inactivation of the β-catenin destruction complex to ultimately upregulate SLUG and β-catenin. In addition, we generated a chimeric anti-ENO1 mAb (chENO1-22) that can decrease cancer cell proliferation and invasion. chENO1-22 attenuated cancer cell invasion by inhibiting ENO1-mediated GSK3β inactivation to promote SLUG protein ubiquitination and degradation. Moreover, chENO1-22 prevented lung tumor metastasis and prolonged survival in animal models. Taken together, these findings illuminate the molecular mechanisms underlying the function of ENO1 in lung cancer metastasis and support the therapeutic potential of a novel antibody targeting ENO1 for treating lung cancer. Significance: This study shows that ENO1 promotes lung cancer metastasis via HGFR and WNT signaling and introduces a novel anti-ENO1 antibody for potential therapeutic use in lung cancer.
Developing, implementing, and validating a social toxicity assessment tool of cancer (STAT-C).
Authors: Abdul-Rahman Jazieh, Hoda Jradi, Omar B. Da'ar, Mohammad Alkaiyat, Yousuf Zafar, Ashwaq Aman Mohammed Alolayan
Journal: Journal of Clinical Oncology (2021)

e24115 Background: The social impact of cancer on patients and their family is well known. Yet, unlike with physical and financial toxicities, no validated tools are available to measure this impact. This study aimed at developing, validating, and implementing a novel social toxicity assessment tool for patients with cancer diagnosis (STAT-C). Methods: Questions were generated through multiple steps including focus groups of patients, their families, and oncology care professionals. Content validity, internal consistency, face validity and factor analysis were conducted. The questionnaire (in Arabic language) was administered to 150 patients with cancer served at King Abdulaziz Medical City, Riyadh, Saudi, Arabia. Results: STAT-C contains 14 items covering three domains: Social Relations domain (eight questions) related to relationship with parents, spouse, children, siblings, friends, members of congregation, and caregiver; Social Activities domain (two questions) measures participation in social events and leisure; and Economic Impact domain (four questions) related to standard of living, finances, and loss of job. The total possible score for each patient for the 14 items in the tool varied between -28 and +28 (Range = 56). Dividing the range by three levels of a socioeconomic toxicity yielded the length of each level, which effectively defined the categories as- Severe social toxicity (SST score: -28 to -9.3), mild social toxicity (MST: -9.2 to 9.5) and no social toxicity (NST: 9.6 to 28). Conclusions: Our study revealed that STAT-C is a valid and reliable tool in assessing the social toxicity of cancer in Arabic-speaking patients. Validating the tool in an English-speaking population is planned. The tool should enable oncology professionals to deliver better patient-centered care as a component of a holistic approach.
Progression of tumors with development of cerebral metastases is accompanied by suppression of thyroid and glucocorticoid functions.
Authors: Valeria A. Bandovkina, Elena M. Frantsiyants, Ayna M. Salatova, Dmitry A. Kharagezov, Oleg I. Kit
Journal: Journal of Clinical Oncology (2021)

e14005 Background: Cutaneous melanoma (CM), breast cancer (BC) and lung cancer (LC) metastasize to the brain most frequently. Early diagnosis of cerebral metastases is challenging and requires new prognostic criteria. Imbalance of thyroid and glucocorticoid hormones changes the growth and development of malignant tumors. The purpose of the study was to identify readily available prognostic criteria for cerebral metastases in cancer patients at various stages of treatment and follow-up. Methods: Blood levels of cortisol and total triiodothyronine (tT3) were determined by RIA (Immunotech, Czech Republic) in patients with BC (n = 50), LC (n = 50) and CM (n = 50) without brain metastases and in patients with BC (n = 25), LC (n = 25) and CM (n = 25) with cerebral metastases. Results: Blood levels of cortisol in BC, LC and CM patients were normal in 63-84% and elevated on average by 1.7 times in 16-37%. Levels of tT3 in LC were normal, and in BC and CM – within the normal limits, but 1.3 times lower than the mean values. In patients with cerebral metastases, cortisol was lower than the norm by 4.9, 2.5 and 3.6 times in 36% BC, 75% LC and 45% CM cases, respectively. Levels of tT3 in all patients with cerebral metastases were lower than the norm or values in patients without metastases by 2 times and lower. Conclusions: Decreased levels of both cortisol and tT3 in patients with BC, LC and CM may serve as one of prognostic markers of possible development of cerebral metastases. The dynamic determination of levels of thyroid and glucocorticoid hormones is required in cancer patients at various stages of treatment and follow-up.
Groupe Francophone des Myelodysplasies (GFM). Treatment of progression of Philadelphia-negative myeloproliferative neoplasms to myelodysplastic syndrome or acute myeloid leukemia by azacitidine : a report on 54 cases on the behalf of the Groupe Francophone des Myelodysplasies (GFM)
Authors: S Thepot
Journal: Blood (2010)
Anlotinib enhanced penpulimab efficacy through remodeling of tumor vascular architecture and immune microenvironment in hPD-L1/hPD-1 humanized mouse model.
Authors: Yunlong Shan, Chongjin Zhong, Qi Ni, Mengying Zhang, Guangji Wang, Fang Zhou
Journal: Journal of Clinical Oncology (2021)

2581 Background: Even though immune checkpoint inhibitor (ICI) such as anti-PD-1 mAb has emerged as effective treatment for tumor regression, the response rate of ICI monotherapy in solid tumor is low. Many studies have demonstrated that the efficacy of combination therapy of ICI and anti-angiogenesis was superior to monotherapy. Penpulimab (AK105), a humanized IgG1 mAb that blocks PD-1 binding to PD-L1, engineered to eliminate FcγR binding and ADCC/ADCP completely. Here, we explore a new combined therapy of penpulimab and anlotinib, an oral multi-targeted tyrosine kinase receptor inhibitor. Methods: MC38-hPD-L1 tumor-bearing B-hPD-1 humanized mouse model were conducted to investigate the effects of anlotinib (1 mg/kg, every day, p.o) or penpulimab (5 mg/kg, twice a week, i.p) alone or in combination. Immunofluorescence was applied to elucidate tumor vessel normalization. In vivo imaging was conducted to detect the distribution of AF647-labelled penpulimab after anlotinib treatment. Flow cytometry and other techniques were performed to investigate intratumoral immune cells. Results: After 3-week treatment, immunotherapeutic administration of anlotinib or penpulimab showed moderate inhibition of tumor growth (tumor volume: 66.5% and 58.4% of control group, respectively), while combined treatment of anlotinib with penpulimab significantly decreased tumor volume to 36.5% of control group. Tissue pathological and blood biochemical results showed no significant toxic and side effects. Immunohistochemistry revealed that anlotinib induced tumor vascular normalization, indicated by decreased CD31 + area, increased α-SMA around tumor vessels and reduced GLUT1 + area. Furthermore, anlotinib markedly enhanced the delivery of AF647-penpulimab into tumors. Combining anlotinib with penpulimab also promoted infiltration and activity of anti-tumoral immune cells by reducing the level of immune checkpoint TIM3 and increasing the IFNγ secretion from T cells. Conclusions: Our work provides a strong scientific rationale for the combination therapy of anlotinib and penpulimab to improve tumor microenvironment and immunotherapy, which highlights the clinical potential for this new combined therapy.
RARE-21. A RARE CASE OF PEDIATRIC SPINDLE CELL ONCOCYTOMA WITH EML4-ALK FUSION
Authors: George Michaiel, Debra Hawes, Samuel Guzman, Ashley Margol, Jaclyn Biegel, Jianling Ji
Journal: Neuro-Oncology (2021)

Abstract A 12 year-old male presented with a 2-month history of intermittent headaches, nausea, and vomiting. Magnetic resonance imaging (MRI) of the brain revealed a 2.2 x 3.5 x 2.6 cm lobulated, sellar/suprasellar mass, mildly T1/T2 hyperintense, with mild homogeneous enhancement and diffusion restriction. He underwent transsphenoidal and right craniotomies for gross total resection of the mass. Pathology demonstrated a hypercellular neoplasm with spindled to ovoid tumor cells arranged in fascicles and tight whirls, consistent with a spindle cell oncocytoma. OncoKids, a DNA- and RNA-based next generation sequencing panel, demonstrated an in-frame EML4 exon 2-ALK exon 19 fusion with a total of 179,872 supporting reads. The EML4-ALK fusion gene is predicted to encode a chimeric tyrosine kinase that facilitates multimerization and autophosphorylation of ALK, and activates its downstream targets, such as RAS/ERK, PI3K/AKT, and JAK/STAT pathways. This fusion is found in approximately 5% of patients with non-small cell lung cancer, a subset of inflammatory myofibroblastic tumors, as well as single cases of pulmonary atypical carcinoid, cholangiocarcinoma, and high-grade glioma. However, it has not been previously described in oncocytoma. Chromosomal microarray analysis demonstrated two interstitial non-contiguous deletions in 2p, and an interstitial deletion in 18q that does not include any known cancer-related genes. The deleted segment in 2p23.3p23.2 includes DNMT3A, which mediates DNA methylation and functions in modification of gene expression. DNMT3A mutations are frequent in hematological malignancies, however their role in oncocytoma is currently unknown. The proximal breakpoint of the deletion in 2p23.3p23.2 is in close proximity to but does not reside within ALK. Spindle cell oncocytoma is rarely reported in the pediatric population, with only one case described in the literature. This is the first case report of an oncocytoma with an EML4-ALK fusion. Additional studies are warranted to confirm its functional effect.
Prognostic value of systemic inflammatory markers in first- and subsequent-line immunotherapy and durability of response in NSCLC.
Authors: Fahmin Basher, Diana Saravia, Gilberto Lopes
Journal: Journal of Clinical Oncology (2021)

e21210 Background: Treatment of advanced non-small cell lung cancer with immune checkpoint inhibitors (ICI) has been shown to yield durable responses. High neutrophil-to-lymphocyte ratios (NLR), low lymphocyte-to-monocyte ratios (LMR) and high platelet-to-lymphocyte ratios (PLRs) have been used as surrogates for increased levels of inflammation in the tumor microenvironment that can predict cancer progression and response to therapy. However, the comparative prognostic role of these markers account for when immunotherapy is utilized has not been explicitly determined. Methods: We performed a retrospective review of 233 patients with advanced stage NSCLC at the University of Miami / Sylvester Comprehensive Cancer Center who received ICI either as first-line (1L) or second-line (2L) therapy and for whom laboratory data, in particular absolute neutrophil, lymphocyte, monocyte, and platelet counts, were available pre-treatment and 4 weeks after initiation of immunotherapy. Results: Using receiver operating characteristic (ROC) curves, we identified cutoff values with optimal prognostic value for NLR (4), LMR (2), and PLR (200). Median age, histology, and smoking history were equivalent across each group. Improved OS was observed in our cohort for patients in which pre-treatment NLR &lt; 4 (54.4m vs. 35.9m, p = 0.0069), LMR &gt; 2 (54.4m vs. 32.3m, p = 0.0016), and PLR &lt; 200 (54.4m vs. 27.5m, p = 0.0007), while PFS was unaffected when looking strictly at these cutoffs. We then observed that PFS could be better predicted after stratifying NLR, LMR, or PLR when taking into account whether ICI was administered as 1L or 2L. We also determined that changes in (Δ) NLR or LMR (but not PLR) by at least 20% between baseline and 4 weeks after initiation of ICI could predict duration of response to ICI. Conclusions: In conclusion, the NLR, LMR, and PLR are powerful surrogates for the tumor microenvironment and can predict responses to ICI in advanced NSCLC when used in the context of previous lines of therapy and subsequent pro-inflammatory changes. Our study shows that ICI used in the first-line setting results in more durable responses, and can overcome an unfavorable tumor microenvironment. In addition, we demonstrate that in NSCLC, durability of responses can be predicted by changes in these systemic inflammatory response markers early after the initiation of ICI.[Table: see text]