bluuebunny/crossref_metadata_2025 huggingface dataset:
Camrelizumab plus apatinib in patients with recurrent and/or metastatic nasopharyngeal carcinoma: A single-arm, multicenter, phase 2 trail.
Authors: Mo Yunyan , Pan Yufei , Zhang Bin , Zhang Jian , Liu Zhengchun , Luo Meiqing , Su Yixin , Jiang Wei
Published: June 2022

e18025

Background: Our previous study demonstrated that apatinib has preliminary clinical benefit in recurrent and/or metastatic nasopharyngeal carcinoma (RM-NPC). Preclinical studies showed the combination of immune checkpoint inhibitors and antiangiogenic drugs produces a synergistic effect in anti-tumor activity. This phase 2 trail evaluated the efficacy and safety of camrelizumab combined with apatinib in patients with RM-NPC. Methods: In this study, patients with RM-NPC received 250 mg apatinib orally once per day plus 200 mg camrelizumab by intravenous infusion every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) assessed according to RECIST version 1.1. The key secondary endpoints included progression-free survival (PFS), overall survival (OS) and safety. The study is registered with. Results: From January 14, 2021 to September 15, 2021, 26 patients with RM-NPC were enrolled in this clinical study with median follow-up duration of 8 months (range:4-12 months). The ORR was 38.5% (10/26), and the DCR was 61.5% (16/26). Median PFS (mPFS) was 6 months. Median OS was not reached. Of the 26 patients, 6 patients (23.1%) had treatment-related grade 3 or 4 adverse events, including anemia(7.7%), stomatitis(3.8%), headache(3.8%), pneumonia(3.8%) and myocarditis(3.8%). No treatment-related deaths occurred in this trial. Conclusions: Camrelizumab plus apatinib had promising antitumor activity and manageable toxicities in patients with RM-NPC, and the mPFS by this combination regimen was longer than our previously reported mPFS by apatinib monotherapy. Larger randomized trials to evaluate this new combination strategy are warranted. Clinical trial information: NCT04350190. [Table: see text]
The predictive and prognostic value of weight loss and body composition prior to and during treatment with immune checkpoint inhibitors in patients with recurrent or metastatic head and neck cancer.
Authors: Willemsen Anna C. H. , De Moor Nina , Van Dessel Jeroen , Bila Michel , Baijens Laura W.J. , Hauben Esther , Van Den Hout Mari , Hoeben Ann , Clement Paul M. , Schols Annemie M.W.J.
Published: June 2022

e18027

Background: Response rates of immune checkpoint inhibitor (ICI) therapy for recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) are relatively low. This study evaluates the predictive and prognostic value of weight loss and changes in body composition prior to and during ICI therapy in R/M HNSCC. Methods: This retrospective multicenter cohort study enrolled ninety-eight patients. Patient, tumor and treatment characteristics were retrieved from health records, including neutrophil and platelet-lymphocyte-ratio (NLR and PLR). Cachexia was defined according to the international consensus (Fearon et al. 2011). Skeletal muscle (SM), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) were evaluated on baseline and follow-up computed tomography scans at the third lumbar vertebrae level. Univariable and multivariable regression analysis were performed for six months progression free survival (PFS6m) and overall survival (OS). Results: Thirty-four patients (35%) experienced significant early weight loss (> 2%) during the first six weeks of therapy. This subgroup presented a significantly higher NLR and PLR at baseline. NLR and PLR were significantly correlated with VAT and SAT index. Independent predictors of PFS6m were lower world health organization performance status (WHO PS) (HR 0.16 [95% CI 0.04-0.54] p = 0.003), higher baseline SAT index (HR 1.045 [95% CI 1.02-1.08] p = 0.003), and early weight loss < 2% (HR 0.85 [95% CI 0.74-0.98] p = 0.03). WHO PS and baseline cachexia in combination with > 2% early weight loss were independent predictors of OS (HR 2.09 [95% CI 1.11-3.92] p = 0.02, HR 2.18 [95% CI 1.13-4.21] p = 0.02). Conclusions: The combination of cachexia at baseline and weight loss during the first six weeks of ICI therapy is associated with worse OS in HNSCC patients treated with ICI therapy. Patients with early weight loss during ICI treatment show an increase in systemic inflammation. The mechanism of how adipose tissue interferes with ICI response needs further investigation.
Improved laryngeal function after neoadjuvant therapy for advanced thyroid cancer: A potential outcome of interest for future clinical trials.
Authors: Abdelhamid Ahmed Amr Hesham , Silver Karcioglu Amanda , Feng Zipei , Shonka David C. , Iwata Ayaka J. , Cabanillas Maria E. , Wirth Lori J. , Zafereo Mark E. , Randolph Gregory W.
Published: June 2022

e18030

Background: Advanced thyroid cancers can invade the recurrent Laryngeal Nerve (RLN) resulting in vocal cord paralysis (VCP). This can significantly impact the surgical strategy given the need to sacrifice the invaded RLN, the potential for bilateral VCP and tracheotomy. Methods: We retrospectively identified patients diagnosed with advanced thyroid carcinomas (of any histology) at 3 high-volume tertiary centers who met the following criteria: treated between 01/2017 and 12/2022, tested for driver/targetable somatic mutations, received targeted neoadjuvant therapy, underwent laryngoscopic exam to assess vocal cords (VC) functional status before, during and after neoadjuvant therapy, and underwent surgery. Results: We identified 6 patients who met the eligibility criteria. Mean age at diagnosis is 69. Five patients were diagnosed with anaplastic thyroid carcinoma, while 1 with papillary thyroid carcinoma. Somatic mutations were detected in BRAFV600E in 6 patients (100%), TERT promoter in 3 (50%) and in PIK3CA & TP53 in 2 patients each (33%). Five patients received dabrafenib/trametinib & 1 patient received lenvatinib. One patient received radiotherapy before neoadjuvant therapy. Baseline laryngoscopic exam detected 5 left-sided VCP and 1 right-sided VCP. After neoadjuvant therapy, 4 patients (67%) regained VC function after 3 months of therapy. By 13.5 months, all patients (100%) regained normal VC function, with a mean time-to-return of VC function of 5 months. The affected RLN could be surgically spared in 5 patients (83%). Conclusions: Use of neoadjuvant targeted therapy resulted in return of VC function in all patients after initially abnormal laryngeal exams, with 67% of patients showing return of function after 3 months. Additionally, neoadjuvant therapy resulted in tumor response sufficient to spare 5 RLNs from surgical resection (83%). Serial laryngoscopic exams during neoadjuvant therapy could guide surgical strategy, impact surgical timing, and provide an additional meaningful treatment outcome. VC function could be used as an endpoint in future neoadjuvant trials. Potential limitations include tertiary center referral bias and selection bias (patients who met eligibility criteria may have favorable trajectory, while patients with aggressive disease who didn’t respond to therapy were excluded). Clinical trials are undergoing to further validate our results. [Table: see text]
Induction chemotherapy using carboplatin and paclitaxel followed by hypofractionated radiation therapy in locally advanced hypopharyngeal and laryngeal squamous cell cancer.
Authors: Abdullah Famya , Adil Allah Rakha , Akhtar Muhammad Saeed , Quraishi Arif Moin , Hashmi Quratul Ain , Sattar Amir , Sanwal Isharat Shehrood , Mateen Abdul
Published: June 2022

e18039

Background: Head and neck cancer (HNC) is one of the most common cancers in Pakistan due to excessive use of chewable tobacco. Locoregional control is not optimum due to advanced stage at presentation and suboptimal cancer treatment facilities. Innovations in treatment schedules are of utmost importance to tackle the problem of overburden of patients and shortage of resources for radiation therapy in the country. The aim of the study is to assess the efficacy of induction chemotherapy with carboplatin and paclitaxel (CP) followed by hypofractionated radiotherapy (HRT) in patients with locally advanced laryngeal and hypopharyngeal cancers. Methods: A total of 68 patients with biopsy proven HNC were included. Patients having primary tumor in larynx (35) and hypopharynx (33) with TNM stage III to IVB were selected. The patients were planned for three cycles of CP every three weeks in a dose of AUC = 5 and 175 mg/m² on day 1 of each cycle respectively. After three cycles of chemotherapy, patients were planned for hypofractionated radiotherapy (HRT). A total of 55 Gray (Gy) was planned with 2.75 Gy per fraction and five fractions a week. Spinal cord dose was limited to 33 Gy. Response Evaluation Criteria in Solid Tumor (RECIST) was used to assess various response rates using computed tomography (CT) six weeks after completion of HRT. Patients were followed for a median of 27.4 months to assess disease free survival (DFS) and overall survival (OS). Results: 61 patients (90%) were available for assessment. Others were excluded due to inability to complete the planned treatment. Eight patients (12%) showed disease progression during treatment and were switched to other form of treatment. Seven patients (10%) showed grade 3 mucosal toxicity and needed treatment interruption. Thirteen patients (19%) showed hematological related grade 1-2 toxicity. The complete response (CR) was seen in 18 (35%), partial response (PR) in 27 (52%) and stable disease SD in 7 (13%) patients. Three year DFS and OS were 45% and 58% respectively. Mean and median DFS (year) were 3.67±0.13 (95% confidence interval [CI] 3.19-3.94) and 4.24±0.43 (CI 3.46-4.52) respectively. Mean and median OS (year) were 3.89±0.11 (CI 3.72-4.15) and 4.12±0.23 (CI 3.87-4.38) respectively. Conclusions: Induction CP followed by HRT is a reasonable in locally advanced laryngeal and hypopharyngeal cancer. A larger phase III randomized trial will be better to define its role before routinely recommending this schedule in these patients.
Cytokine-induced memory-like (CIML) NK cells and association with circulating immune microenvironment.
Authors: Xiao Shanshan , Fan Tongqiang , Wang Qian , Wang Tao ,   Hangzhou Repugene Technology Co,.Ltd
Published: June 2022

e18042

Background: Cytokine-induced memory-like (CIML) NK cells are attractive for adoptive cell therapeutic approaches due to their key characteristics which include anti-tumor responses, prolonged proliferation and persistence in vivo. Several NK cell subsets have been reported in human and mice, but their heterogeneity and trajectories in human peripheral blood remains poorly characterized. We aimed to evaluate the developmental trajectories and prognosis outcomes of several CIML NK subsets between HPV+ and HPV- HNSC patients. Methods: A publicly available scRNA-seq dataset (only CD45+PBMC data sets were used) (Kürten et al., 2021) was obtained and stratified by two definitions of CIML NKs: (1) increased granzyme B mRNA expression and (2) preactivated with iterleukin-12 (IL-12), IL-15 and IL-18. Single-cell analysis was performed, followed by sub-clustering of NK populations. Results: 4,794 NK cells from 6 HPV+ and 11 HPV- HNSC patients were analyzed in our study. Expression profiles showed that these NK cells were CD56dimCD16+CD57-NKs. Further investigation showed that these cell populations exhibit a cytokine-induced memory-like phenotype, including increased granzyme B mRNA and preactivated with IL-12, IL-15 and IL-18. Transcriptomic profiles demonstrated that CIML NK cells can be classified into three subsets, including Bl1, Bl2, and Bl3, where Bl1 and Bl3 were found to be consistent with the previous studies, Bl2 was a newly identified NK cluster in this study. Pseudotime analyses suggested that CIML NK cells transitioned from Bl3 (is in cytolytic state) to Bl2, and then (maintains intermediate cell states) to Bl1 (supports cytotoxic activity), regardless of HPV status. There were 20, 60, and 26 Up-regulated genes in Bl, Bl2, and Bl3 in HPV+ patient compared to HPV- patients, respectively. Biocarta pathway analyses showed that NK cell pathway was highly enriched in all NK subsets from HPV+ patients, instead of HPV- patients, indicating a developmental independent characteristic. Survival analyses showed poor prognosis outcomes for high expressed CIML NK signatures in no matter HPV+ or HPV- patients. Conclusions: We investigated CIML NK cells in human peripheral blood and found that Bl1, Bl2, and Bl3 NK clusters showing the developmental patterns of increased cytotoxicity independent of HPV status. The Bl2 is a novel NK cell cluster which presents intermediate cell states. The cluster signatures were correlated with poor clinical outcomes, highlighting its’ potential clinical values for CIML NK-targeted immunotherapies.
Spatial transcriptomics unravels novel signaling patterns at the leading edge of oral squamous cell carcinoma.
Authors: Arora Rohit , Cao Christian , Kumar Mehul , Chanda Ayan , Samuel Divya , Matthews Wayne , Chandarana Shamir , Hart Robert , Dort Joseph C. , Hyrcza Martin , Bose Pinaki
Published: June 2022

e18043

Background: Head and neck cancer is the 6th most common cancer worldwide. Oral squamous cell carcinoma (OSCC) is the most prevalent head and neck cancer that is characterized by aggressive local invasion and metastasis. Despite the leading edge (invasive front) of the tumor being a driver of OSCC pathophysiology, its biology and clinical relevance have not been fully characterized. We used spatial transcriptomics to explore signaling patterns within the leading edge and tumor core. Methods: Fresh-frozen, surgically resected OSCC samples from three HPV-negative OSCC patients were profiled using the 10x Genomics Visium Spatial Gene Expression platform. Leading edge and tumor core regions were defined by pathologist annotations and expression of previously identified edge and core gene signatures from the literature. Spatial differential gene expression (DGE) analysis and pathway analysis was performed using the Seurat package and Ingenuity Pathway Analysis (IPA), respectively. Cell-cell interaction networks were reconstructed using the CellChat package. Results: The leading edge and tumor core displayed unique transcriptional and signaling profiles that were conserved across all three OSCC patient samples. DEG analysis revealed 31 genes enriched in the leading edge and 62 genes enriched in the tumor core with a log2FC > 0.58 and adjusted p-value < 0.01. The top genes upregulated in the leading edge were FN1, COL1A1, COL1A2, IFITM3, and SPARC. Top tumor-core genes included CRCT1, LCE3D, DEFB4A, SPRR2A, and CNFN. IPA analysis of upregulated DEGs in the leading edge and tumor core predicted the activation of wound healing and GP6 signaling pathways, and activation of intrinsic prothrombin activation and MSP-RON signaling pathways, respectively. Cell communication analysis revealed that the leading edge had higher intercellular signaling than the tumor core. Upregulated leading edge cell signaling modules included collagen, CD99, CSPG4, and non-canonical WNT pathways, which have been linked to tumor invasion, metastasis, and adhesion. COL1A1 and COL1A2 ligands and CD44 and SDC1 receptors were upregulated in leading edge signaling. The tumor core was enriched for ANGPTL and PERIOSTIN cell signaling modules. Conclusions: This is the first study to characterize the tumor core and leading edge of OSCC tumors using spatial transcriptomics. Further investigation of the therapeutic potential of identified signaling pathways may improve OSCC outcomes.
Tumor mutation burden (TMB) and Notch1 gene alteration are associated with short disease-free survival in early laryngocarcinoma.
Authors: Chen Xi , Gong Xiao-yang , Chen Hai-bing , Chen Dong-sheng , Zhao Lele
Published: June 2022

e18049

Background: Patients with early-stage laryngocarcinoma, even stage T1-2N0, are at substantial risk of relapse and death. Molecular alterations are thought to be associated with the immune microenvironment in the tumor and to have an important role in predicting the prognosis. In this study, we explored the distinct features of molecular alterations and immune-related gene expression and examined the relationship between molecular alterations and prognosis. Methods: A total of 42 stage T1-2N0 laryngocarcinoma patients were enrolled, no patients received chemotherapy or immunotherapy before surgery, tissue samples from radical operation were collected. Of these, 23 cases developed disease progression within 24 months after operation [shorter disease-free survival (shorter DFS)], while others 19 cases showed longer DFS over 24 months (longer DFS). Distinct features of molecular alterations and immune-related gene expression in Formalin-fixed paraffin-embedded (FFPE) samples through using DNA sequencing and an immune oncology panel RNA sequencing platform were performed. Results: A total of 293 mutations were detected within 42 patients, the median number of mutations in the short-DFS group was higher than that in the long-DFS group (9.0 vs. 5.2; P = 0.045). No correlation between mutation type and DFS was found. TMB-high (Top 25%) was associated with worse DFS (TMB-L: Not reached, TMB-H: 11.5 months, p = 0.036; HR, 2.4; 95% CI 1.05 to 5.48). Among 522 cancer-related genes, alterations in 51 genes were detected. TP53 (33/42, 79%) was the most common mutation gene in the entire cohort. Mutations of LRP1B (30.4% vs 5.3%, p = 0.039) and Notch1 (21.7% vs 0%, p = 0.030) were significantly occurred in the short-DFS group, patients with Notch1 mutation had a significantly shorter DFS period (P = 0.0012). Univariate and multivariate analysis showed that high TMB and Notch1 mutation were independent prognostic factors in DFS. Conclusions: In early-stage laryngocarcinoma, Notch1 mutation and high TMB were associated in patients with short-DFS, indicating the potential prognostic biomarkers and therapeutic molecular targets for early-stage laryngocarcinoma.
Voxel-based radiomics outlines spatial heterogeneity of cerebral radiation necrosis (RN) associated with bevacizumab (Bev) response in head and neck radiotherapy (RT) patients.
Authors: Tan Hong Qi , Cai Jinhua , Sim Adelene Y.L. , Huang Luo , Chua Melvin L.K. Lee Kiang , Tang Yamei
Published: June 2022

e18063

Background: RN is a debilitating toxicity of head and neck RT, with incidences of 4% to 24%. Bev is a promising drug for managing RN, but there is currently no biomarker that could predict a priori if a patient would benefit from Bev. Here, we aimed to use radiomics to predict Bev response. However, current radiomics tools suffer from issues of interrater contouring variability and explanability of the radiomics models. We therefore investigated a voxel-based radiomics approach to characterize the spatial heterogeneity of RN, and define subregions that are associated with Bev response. Methods: 118 consecutive nasopharyngeal carcinoma (NPC) patients who were diagnosed with RN post-RT, and were treated with Bev between Jul 2012 and Mar 2019 at the Sun Yat-Sen Memorial Hospital were enrolled into the study. 77 patients with 101 brain lesions treated between Jul 2012 and Dec 2017 were assigned to the training set, and 41 patients with 51 brain lesions treated between Jan 2018 and Mar 2019 were used for validation. All patients received Bev prescribed at 5 mg/kg every fortnightly for up to 4 courses. We extracted voxel-based radiomics features from each segment drawn on T2 FLAIR MRI images, followed by a 3-step analysis (individual- and population-level clustering, before delta-radiomics) to obtain a clustered heat map of subregions within the RN lesion. Anatomical correlation to areas of edema, necrosis, and their interphase was performed. Delta-radiomics tracked the ∆ of each cluster to Bev. Features were then extracted from each radiomics cluster for model building. Results: 71 (70.3%) and 34 (66.7%) lesions had documented radiological responses to Bev in the training and validation sets, respectively. Responders (N = 105) and non-responders (N = 47) showed a 71.8% (IQR: 54.7-87.5) and 13.2% (IQR: 7.98-21.4) reduction in RN volumes, respectively. Five optimal clusters were determined using the shoulder method with ΔK metric. Spatial analyses revealed that 2 of the 5 clusters were associated with the edema areas, with 92.6% and 74.3% of the voxels located within this anatomic subregion. The two corresponding clusters were significantly associated with a response to Bev (Odds ratio [OR]: 11.12 (95% CI: 2.54-73.47), P = 0.004; OR: 1.63 [1.07-2.78], P = 0.042). Finally, we developed and validated a clinicoradiomics model based on features extracted from the 2 clusters that improved the prediction of Bev response, compared with a clinical-only model for both the training (AUC 0.852 vs 0.755) and validation (AUC 0.816 vs 0.691) cohorts. Conclusions: Our spatial radiomics approach revealed anatomic subregions that contain relevant radiomics features that could predict Bev efficacy in the treatment of RN in NPC patients. This method would improve the interpretability of radiomics, compared with current methods that lack spatial resolution.
Oncological safety of harvesting local flaps from the neck in clinically node positive patients with oral squamous cell carcinoma.
Authors: Saha Aditi Subrata , A Anoop , Vijay Sandeep , Nair Raveena , Thomas Linu , George Rithin
Published: June 2022

e18065

Background: Reconstruction of complex orofacial defects following tumour resection has always posed as a challenge for clinicians for providing functional and morphological outcomes. Though microvascular free flaps revolutionized reconstruction, local flaps provide a viable alternative in resource constraint settings. Oncological safety of harvesting local flaps has always been a matter of debate in oral squamous cell carcinoma due to proximity of nodal stations. Available literature on oncological safety is limited to clinically node negative patients. The purpose of this study was to evaluate the oncologic safety of local flaps in clinically node positive patients. Methods: Retrospective analysis of data available of all patients diagnosed with clinically node positive oral squamous cell carcinoma who underwent modified radical neck dissection at Malabar Cancer Centre during the period January 2012 to December 2017 was done. Demographic profile, tumour characteristics and pathological outcomes were compiled. The factors included were pathological tumour, nodal stage, levels of nodes involved, extranodal extension, choice of flap and site of recurrence. Fisher's exact test was used to compare recurrence patterns between local and regional flaps. Results: A total of 309 clinically node positive patients were analyzed with a median follow up of 4 years. Overall incidence of pathologically proven nodal metastases to ipsilateral levels Ia Ib, II, III, IV and V were 8.1%, 35.3%, 39.5%,15.5%, 2.9% and 1.3% respectively. Level Ia was most commonly involved in buccal mucosa and tongue cancers. Levels Ib, II, III were most commonly involved in tongue and buccal mucosa cancers. Level IV was commonly involved in tongue cancers while level V in cancer of retromolar trigone. Local flaps analyzed were submental flap (2.6%), supraclavicular flap (2.6%), infrahyoid flap (2.6%), sternocleidomastoid muscle flap (4.5%), nasolabial flap (1.3%), facial artery myomucosal flap (1.6%). Pathological nodal positivity was 60% and 52% in local and regional flaps respectively. Amongst the patients who had reconstruction with submental flap there were no nodal recurrences at level Ia, only 1 patient had recurrence at flap site. Amongst the patients who had reconstruction with supraclavicular flap there was 1 patient with pathological involvement of level V as per histopathological report but no nodal recurrences at level V. There was no difference in pattern of nodal recurrence between local and regional flaps (p = 0.436). Conclusions: This retrospective analysis is the first of its kind analysing the oncological safety of harvesting local flaps in clinically node positive oral squamous cell carcinoma. Thus, with appropriate management of the levels Ia and V nodal compartment, oncologic outcomes are not compromised, thereby making it oncologically sound to harvest local flaps in N+ neck.
Neoadjuvant trial with toripalimab, albumin paclitaxel, and cisplatin on pathological response in locally advanced resectable oral squamous cell carcinoma (Illuminate Trial).
Authors: Zhong Lai-Ping , Huang Ying-ying , Sun Jing-jing , Li Jun , Dong Min-jun , Zhu Guopei , Li Jiang , Ju Wu-tong
Published: June 2022

e18067

Background: In patients with locally advanced resectable oral squamous cell carcinoma (OSCC), major pathological response (MPR) to neoadjuvant therapy may translate into improved survival. The combination of anti-PD-1 and chemotherapy as neoadjuvant protocol has not been well reported in OSCC. Methods: The prospective single arm trial (NCT04473716) was performed to evaluate the neoadjuvant therapy with anti-PD-1 (Toripalimab) and chemotherapy (albumin paclitaxel/cisplatin) in OSCC patients at clinical stage III and IVA (AJCC 2018). The patients received two cycles (21 days each) of intravenous albumin paclitaxel (260mg/m2), cisplatin (75mg/m2) and Toripalimab (240mg) on day 1 and day 22. Radical surgery was performed within two weeks after neoadjuvant therapy. Post-operative radiotherapy/chemoradiotherapy was performed within 1.5 months after surgery. The primary endpoints were MPR and safety. Primary tumors were assessed for the percentage of residual viable tumor cells on HE staining, and tumor with no more than 10% viable tumor cell was considered as MPR. Results: From Nov. 2020 to Apr. 2021, 20 patients were enrolled, including 16 males and 4 females, at clinical stage III (16) and IVA (4). They aged from 19 to 75 (median 54) years . The primary tumor site was eight tongue, six mouth floor, three gingiva, two retromolar trigone and one buccal mucosa. The neoadjuvant therapy was well-tolerated with low incidence of grade 3-4 adverse events (AEs) including 5% grade 4 neutropenia, 10% grade 3 leukopenia, 5% grade 3 neutropenia, hypokalemia, vomiting, and rash each. Common grade 1-2 AEs included baldness/rash/itch/pain/fatigue, AST/ALT/uric acid elevation, nausea/vomiting/diarrhea, hyperbilirubinemia, proteinuria, neutropenia/leukopenia. All AEs were relieved after expectant treatment, the subsequent standard treatment was not delayed. According to pathological evaluation, the MPR rate was 60% (12/20), including 30% (6/20) pCR. According to RECIST 1.1, radiological evaluation on neoadjuvant therapy showed two CR, ten PR, seven SD and one PD. It was significantly consistent between pathological and radiological evaluation in linear regression analysis ( P＜0.0001). Combined positive score (CPS) of PD-L1 expression in biopsy was evaluated in 19 patients, MPR was archived in all 4 patients with CPS≥10, in 6 out of 8 patients (75%) with CPS≥1, and in 5 out of 11 patients (45.5%) with CPS < 1. Conclusions: Neoadjuvant therapy with combination of Toripalimab, albumin paclitaxel, and cisplatin in resectable OSCC patients is safe and well-tolerated, with high MPR rate. Clinical trial information: NCT04473716.
Metronomic systemic PCm (paclitaxel, carboplatin + metronomic) neoadjuvant chemotherapy in head and neck cancer.
Authors: Singh Gunjesh Kumar , Prabhash Kumar , Patil Vijay Maruti , Noronha Vanita , Joshi Amit , Menon Nandini Sharrel , Singh Pragya , Qayyumi Burhanuddin , Singh Ravikant
Published: June 2022

e18073

Background: Neoadjuvant chemotherapy (NACT) in head and neck cancers (HNC) with taxane, platinum, 5-FU (TPF) regimen is both toxic as well as difficult to use in resource-constrained settings. We used a novel combination of weekly chemotherapy and oral metronomic chemotherapy (OMCT) and assessed the efficacy and safety of this combination as NACT in locally advanced HNC patients. Methods: This is a retrospective analysis of prospectively maintained data. 56 patients with technically unresectable HNC received NACT with paclitaxel (80mg/m2) plus carboplatin (AUC2) - weekly schedule and OMCT (methotrexate 9mg/m2 once a week, celecoxib 200mg twice daily, and erlotinib 150mg once daily) - PCm regimen. Patients were assessed clinically and radiologically after a minimum of six cycles for resectability. The radiological response was evaluated as per RECIST 1.1. We report the response rate, resectability, survival, and tolerance of this NACT regimen. Results: The median age of the patients was 41 years. Fifty-two patients (92.9%) were male. Buccal mucosa (60.7%) and oral tongue (17.9%) were the commonest sites of primary seen followed by alveolus (10.7%), the floor of mouth (5.4%), and larynx (5.4%). AJCC 2017 stage IVA and IVB disease were present in 64.3% and 35.7% of patients respectively. Edema up to zygoma (44.6%), high ITF involvement (19.7%), technically unresectable nodal disease (16.1%) and disease reaching up to vallecula (12.5%), or hyoid bone (5.4%), and nodal encasement (180-270 degree) of the internal carotid artery (1.8%) were the reasons for technical unresectability. The median number of NACT administered was six. The tumor showed partial response in 54 (96.4%) patients, 2 (3.6%) patients had stable disease and none of the patients had tumor progression. Surgery was planned in 47 (83.9%) patients after NACT, however due to logistic issues only 35 (62.5%) patients could undergo surgery. Pathological complete response was seen in 27 (48.21%) patients. After a median follow-up of 7.36 months, median PFS was not reached in the whole cohort and surgery group of patients, whereas it was 5.23 (95% CI, 4.08 -6.38) months in the non-surgery group. Median OS was not reached in our cohort. Common grade 3/4 toxicities (CTCAE 5.0) observed were oral mucositis in 6 (10.7%) patients, diarrhea in 4 (7.1%), and febrile neutropenia in 1 (1.7%) patients. Conclusions: Weekly scheduled PCm is an efficacious and well-tolerated regimen and can easily be administered in resource-constrained settings.
Factors associated with baseline quality of life in patients with oral cavity and oropharyngeal cancer.
Authors: Deng Jie , Murphy Barbara A. , Andersen Lucy , Dietrich Mary S.
Published: June 2022

e18079

Background: Baseline quality of life (QOL) predicts for survival in head and neck cancer patients. The purpose of this study was to identify factors contributing to baseline QOL in patients with newly diagnosed oral cavity or oropharyngeal cancer (OCOPC) in order to identify potential targets for intervention. Methods: 115 patients with OCOPC completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, Hospital Anxiety and Depression Scale, and Brief Health Literacy Screen (BHLS). Pearson correlation and ANOVA statistics were used to analyze the data. Results: The median global health-related QOL score was 66.7 (IQR: 50, 83.4); 35.7% of participants reported anxiety and 18.3% reported depressive symptoms (HADS ≥8); 30.8% of patients had BHLS values of ≤ 9. Factors associated with significant decrease in global health-related QOL score: household income of < $20,000/year (p = .010); low health literacy (p = .021); having symptoms of anxiety (p < .001); having depressive symptoms (p < .001); and non-HPV associated cancer (p < .001). Increased tumor stage, older age, single/widowed marital status, and unemployment were associated with the lower scores on the physical QOL subscale (p < .05). Increased tumor stage was associated with lower scores on role and social QOL subscales (p < .05), and younger age was associated with lower scores on emotional QOL subscale (p < .05). Conclusions: Baseline QOL is associated with socioeconomic and disease-related determinants. Clinical trial information: NCT02412241.
Perceptions towards breast and cervical cancer development and screening in transgender and nonbinary persons.
Authors: Roznovjak David , Petroll Andrew , Lakatos Anne , Narayan Raj , Cortina Chandler Scott
Published: June 2022

e18500

Background: Approximately 1.4 million adult Americans identify as transgender (TG) or non-binary (NB), a number that has steadily increased over time. In this population, cancer risk is unclear, and screening and treatment guidelines are lacking. We sought to assess TG and NB persons’ perceptions towards breast and cervical cancer screening, risk of cancer development, and thoughts towards gender-affirming hormone therapy in the setting of a hormone-receptor positive breast cancer. Methods: A single-institution online survey was administered from October 2021-January 2022 at our comprehensive LGBTQ+ Inclusion Health Clinic. Participants with female sex at birth were asked about breast and cervical cancer, while those assigned male sex at birth were exclusively asked about breast cancer. A 5-point Likert scale was used to assess attitudes toward cancer screening and concerns regarding cancer development. Results: 40 patient responses were collected: 13% were TG women, 45% TG men, 23% NB, and 20% identified as other (i.e., agender, genderqueer, etc). 71% were assigned female sex at birth (59% of whom had chest masculinization surgery), 27% were assigned male sex at birth, and one individual was intersex at birth. 52.5% were age < 30, 84% were Caucasian, 65% had at least a bachelor’s degree, and all but one respondent had health insurance. The majority reported they were not familiar with breast (77%) or cervical (60%) cancer screening recommendations for their sex-assigned at birth or current gender identity. 23% reported concern regarding breast cancer development and cited family history as the primary reason. In patients age > 40, 50% had a mammogram (MMG) in the past 10 years. When presented with information regarding screening MMG and automated breast ultrasonography (ABUS), 78% reported they would prefer ABUS over MMG for breast cancer screening. 84% of respondents were currently using or had previously used gender-affirming hormone therapy, and of these, 61% reported they would stop therapy in the event they developed a hormone-receptor positive breast cancer. In patients assigned female sex at birth, 25% had a hysterectomy and, in those who still had a cervix, 50% reported having a Pap smear in the past 5 years and 38% were concerned about cervical cancer development. Conclusions: This survey identified that > 60% of TG and NB individuals are unaware of breast and cervical cancer screening guidelines, > 20% are concerned about breast and cervical cancer development, and < 50% of patients eligible for breast and cervical cancer screening had undergone screening in recent years. Additionally, in the setting of a hormone-receptor positive breast cancer, only 61% would consider stopping gender-affirming hormone therapy. Further data on the risk of breast and cervical cancer development and incidence in TG and NB persons is needed to inform optimal screening and treatment guidelines.
Improvements in myeloma specific survival over the last two decades.
Authors: Mankan Nidhi , Nooka Ajay K.
Published: June 2022

e18503

Background: Improvement in overall survival (OS) have been observed among myeloma patients over the last several decades, mainly due to improvement in therapeutic options. For a disease, more common in the elderly (median age of diagnosis of 70), and a median reported OS exceeding 10 years (Joseph et al JCO 2020), reaching normal life-expectancy for a myeloma patient has become more realistic now than ever before. In this context, where the competing risks for mortality for myeloma patients are higher, we have evaluated the changes in the myeloma specific survival (MSS) using a population-based database Surveillance, Epidemiology, and End Results (SEER)-18 database. Methods: Interrogation for International Classification of Diseases (ICD) for Oncology 3rd edition histology codes 9731/3 resulted in 65848 cases. After excluding 1360 cases of extraosseous plasmacytoma and 2011 cases of solitary plasmacytoma of bone, a total of 62477 cases of myeloma were found. 9322 cases were excluded due to myeloma not being the primary malignancy, leaving a total of 53155 cases with active follow for the primary analysis. OS and MSS were estimated using the Kaplan-Meier method. Improvements in OS and MSS were compared by 4 eras (1975-88; 1989-1998; 1999-2008; 2009-2018) by race and gender. Results: White patients (40040 -75.3%) and males (28104 -52.9%) comprised majority of the study population. 9495 black patients (17.9%) and 3004 Asian/Pacific Islanders (5.7%) were the other major racial groups included in the analysis. The median OS for myeloma patients in the era 1975-1988 was 24 months (95% CI 23.22-24.77) while the simultaneous median MSS was 32 months (95% CI 31-32.99). Significant improvements in OS occurred by the era of 2008-2018 (56 months (95% CI 54.31-57.69). Improvement in MSS was more prominently observed during this era - 87 months (95% CI 83.2-90.80). The OS and MSS for each of the groups by gender and race have been tabulated in table. Conclusions: OS and MSS have improved over the last two decades, more prominently in the last decade. Improvement in MSS clearly highlights the fact that myeloma as the primary cause of death has declined over the last two decades among most groups of patients and it is encouraging to see the benefit extending to the minorities. Future studies may incorporate MSS as an endpoint, which might accurately reflect the benefit offered by the newer safer therapeutics.
The effect of race, employment, and poverty on outcomes in chimeric antigen receptor therapy for DLBCL patients.
Authors: Johnson Grace , Patel Kedar , Jain Michael D. , Blue Brandon Jamaal
Published: June 2022

e18506

Background: Limited information is known about how socioeconomic (SES) factors contribute to outcomes after CAR T-cell therapy for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). While racial and SES disparities have been demonstrated to effect outcomes after Autologous Stem Cell Transplant for DLBCL patients, little is known about this association after CAR T. Methods: Using data from Moffitt Cancer Center's electronic medical record system, we retrospectively evaluated patients diagnosed with DLBCL at our center who underwent CART therapy (n = 200). Data was analyzed by residential area deprivation index (ADI) for patients receiving CAR T therapy for R/R DLBCL at a single tertiary care center. Survival and CAR T-related toxicity outcomes were evaluated based on patient baseline characteristics, disease features, and demographics using multivariable Cox proportional-hazards (PH) regression model and multivariable logistic regression model. Patient socioeconomic status was represented by area deprivation index ranking mapped through 9-digit zip codes. Results: The study included 200 patients receiving CAR T therapy at Moffitt Cancer Center for R/R DLBCL; median age was 65; 46.8% were female, 53.2% male; 89.8% white, 10.2% non-white; median ADI rank of 4. As for disease characteristics; 18.9% had double/triple hit lymphoma by FISH for MYC and BCL2 or 6 translocations; 83.6% had extranodal disease sites. Patients were treated with a median of 3 prior lines of therapy, and most patients (81%) had stage III/IV lymphoma at time of leukapheresis for CAR T. 8.38% of patients experienced grade 3 or higher cytokine-release syndrome (CRS), and 34.6% of patients experienced grade 3 or higher neurotoxicity. Area deprivation index and education level did not significantly contribute to overall survival when adjusted for other clinical features on multivariable Cox PH regression analysis. However, unemployment negatively impacted overall survival (HR = 4.296, P = 0.0243). Progression-free survival was unaffected by ADI, education level, or employment. In terms of CAR T-related toxicities, demographic features did not affect the risk for grade 3 CRS on multivariable logistic regression model. On Wilcoxon rank testing, area of deprivation indices did not significantly differ among patients with or without grade 3 CRS. Conclusions: These results suggest that ADI and other SES factors do not significantly contribute to progression free survival, CRS or neurotoxicity. This study shows unemployment was a significant predictor for poor overall survival after CAR T in patients with DLBCL. This is the first study to evaluate the significance of SES, race, and employment on DLBCL patients after CAR T. Future efforts should be used to investigate measures to increase employment and understand factors associated with unemployment.
Epidemiological and clinical characteristics of patients with cervical cancer and their care pathway in Rio de Janeiro, Brazil.
Authors: Emmerick Isabel M , Vinhal Faria Lara , Castanheira Debora , lazzaroni Moraes Elaine , Sobreira da Silva Mario Jorge
Published: June 2022

e18512

Background: Cervical cancer (CC) is one of the most common cancers in Brazil. This study analyzes the epidemiological and clinical characteristics of CC patients from 2012 to 2017 and their care pathway in Rio de Janeiro, Brazil, considering the municipal and state regulations. Methods: Retrospective study using interrupted time series, including women registered in the Hospital Cancer Registry from January 2012 to December 2017. The interventions analyzed were the implementation of the municipal (August 2013) and state (June 2015) regulation for the treatment of CC in Rio de Janeiro. The main outcomes were (A) Individuals from the metropolitan region I (%); (B) referred by the public sector (%); (C) Group I or II staging (%) (D) Patients who received surgery as first treatment (%) (E) positive outcome (%). Results: 3,460 women were included, 71% were 30 to 59 years old. (A) Individuals from the metropolitan region I accounted for over 68% of the patients, with a statistically decrease after municipal regulation and an increase after state regulation. (B) The public sector referred more than 85% of patients by the end of the period, and despite less than 60% of patients diagnosed with stage I and II (C) the percentage of surgery (D) and positive outcomes (E) were increased over time. Conclusions: Municipal and state regulations organized the flow of patients nevertheless is important to invest in infrastructure to increase early detection, aiming to improve equity of access.[Table: see text]
Clinical utility of widespread germline testing of cancer patients in a diverse community cancer clinic.
Authors: Patel Kashyap B. , Oh William K. , Jun Tomi , Naidu Sashi , Nathwani Nyati , Hansen Gabriel , Hubert Adara , Mukhi Hirangi , Chhadwa Shilpa , Zabala Valerie , Gill Sonia , Branchcomb Randall , Mehta Dhwani , Nixon Sandra , Kodali Ashima , Zimmerman Michelle
Published: June 2022

e18537

Background: Identification of germline mutations can determine prognosis, inform targeted therapies, allow risk-reducing interventions, and suggest additional cancer screenings in patients and their biological relatives. Large prospective cohort studies have been historically skewed towards wealthier socioeconomic populations that lack ethnic diversity and vastly underrepresent African Americans. Recently, small studies outside of standard clinical guidelines reveal detection of pathogenic variants in germline testing with significant clinical ramifications. We present our single center experience of prospective germline testing in a small community clinic in suburban and rural South Carolina with understudied real-world populations. Methods: We performed germline testing, outside of guidelines, in patients presenting at earlier age or with either rare tumors, or recurrent/multiple malignancies. This prospective, observational cohort included a suburban and rural underserved population where approximately 30% identify as African American. Patients were counselled about testing that performed outside of guidelines. Results: We identified 67 individuals outside the guidelines concordance, compromising of 45 male and 22 female patients, within the first 6 months of this prospective, observational cohort. Patients reported race as African American (14), White (50), or Asian American (3). Rare germline findings included Li Fraumeni syndrome, Fanconi’s syndrome, Perelman’s disease, and Von Hippel Lindau’s disease. We summarize our findings in the attached table. Conclusions: There are limited studies that report prevalence of germline findings in cancer patients who are unselected by clinical practice guidelines. Studies also lack representation of ethnic minorities. Recently published data on the clinical utility of broad-based germline testing of all incoming patients suggest current practice of guidelines and genetic counselor recommended testing should be re-examined for broader testing for all incoming cancer patients in a more inclusive manner.[Table: see text]
Evaluating predictors of food insecurity among patients with cancer in the safety-net setting.
Authors: Velazquez Manana Ana I. , Borno Hala , Trejo Evelin , Zhang Sylvia , Rodriguez Saldana Abigail A. , Leung Ivan C. , Seligman Hilary K. , Lin Tracy Kuo
Published: June 2022

e18550

Background: Patients with cancer, especially minority and low-income individuals, are at increased risk of financial toxicity and food insecurity. The COVID-19 pandemic has added dire economic challenges to vulnerable populations leading to a global increase in food insecurity. We sought to evaluate the severity and predictors of food insecurity among low-income patients with cancer. Methods: We conducted a cross-sectional multi-lingual survey (i.e., English, Spanish, and Chinese) on a convenience sample of patients with cancer who receive oncologic care at a safety-net hospital. Food insecurity and financial toxicity were measured using validated scales [i.e., US Department of Agriculture Household Food Security Survey and the Comprehensive Score for Financial Toxicity (COST)]. The primary outcome was food insecurity during COVID-19 and predictors of interest included sex, financial toxicity, insurance change, and degree of acculturation. Data was summarized using descriptive statistics and we explored associations between food insecurity and predictors of interest using bivariate regression. Results: A total of 140 patients participated in the study, of whom 56% were male and 47% were 50-64 years old. The most common cancer diagnoses were breast cancer (33%), followed by prostate (13%) and lung cancer (12%). The diverse study participants self-reported being 42% Hispanic/Latinx, 33% Asian, 18% Black or African American, and 14% White. Over half (52%) reported an annual household income ≤$24,999 and 50% experienced a decrease in income during the COVID-19 pandemic. The median COST score was 24 (IQR: 19-31) with 41% experiencing financial toxicity (COST < 26). Most participants experienced food insecurity, including 42% with low food security and an additional 19% with very low food security. In bivariate analysis, increasing financial toxicity (i.e., lower COST score) was associated with a 21% increased risk of very low or low food security (95% CI: 1.11-1.32) and 13% increased risk of low food security (95% CI: 1.05-1.21). Male sex was associated with 312% increased risk of very low food insecurity when compared to female sex (95% CI: 1.02-9.55). Acculturation and changes in insurance coverage were not associated with increased risk of food insecurity. Conclusions: Food insecurity was highly prevalent in this multi-ethnic cohort of low-income patients with cancer. Interestingly, male sex was significantly associated with increased risk of very low food insecurity. Further analyses should explore this potentially at-risk population, their access to nutrition-related support, and the impact of food insecurity in cancer outcomes.