tbuckley/cabot-search huggingface dataset:
Outcomes of combined immunotherapy and palliative radiotherapy in patients with recurrent/metastatic head and neck cancers.
Authors: Yanshuang Cheng, Juan Wang, Ji Sun, Yahua Zhong, Qiuji Wu
Journal: Journal of Clinical Oncology (2024)

e18002 Background: Immunotherapy has revolutionized the treatment for recurrent/metastatic head and neck cancers (R/M HNC). It is uncertain whether the combination of immunotherapy and radiotherapy can provide survival benefits for R/M HNC. Methods: This study included patients with R/M HNC who underwent immunotherapy in our institute from November 2018 to October 2022. All patients received intravenous PD-1 inhibitors every 3 weeks. Palliative radiotherapy was administered to localized lesions for symptomatic treatment purposes in addition to systemic therapies. Tumor response was evaluated using RECIST1.1 criteria. The primary outcome measures were progression-free survival (PFS) and overall survival (OS). Other outcome measures were disease control rate (DCR) and objective response rate (ORR). The Kaplan-Meier method was utilized for survival analysis, and univariate and multivariate Cox regression analysis was conducted to identify prognostic factors associated with PFS and OS. Results: We included 129 R/M HNC patients. The median follow-up time was 14.0 months. The median number of immunotherapy courses received was 4 (range: 1-60). During immunotherapy, 43 patients received palliative radiotherapy, targeting primary tumors, lymph nodes, metastasis in liver, lung, bone, and other sites. Following the treatments, 16 (12.4%) patients achieved complete response (CR), 44 (34.1%) achieved partial response (PR), 35 (27.1%) had stable disease (SD), and 34 (26.4%) had progressive disease (PD). The ORR was 46.5% and the DCR was 73.6%. The group receiving immunotherapy combined with palliative radiotherapy had higher ORR (65.1% vs 37.2%, p = 0.005) and DCR (90.7% vs 65.1%, p = 0.004) than those without palliative radiotherapy. The PFS (15.0 months vs 4.0 months, p = 0.0027) and OS (not reached vs 26.0 months, p = 0.036) were improved in patients receiving palliative radiotherapy compared to those not. Patients who had received prior radiotherapy (n = 81) had a shorter PFS (4.0 months vs 14.0 months, p = 0.014), while there was no difference in OS (p = 0.16). We further showed that patients had better PFS (20.0 months vs 2.0 months; p &lt; 0.0001) and OS (43 months vs 17 months; p = 0.0043) when they received more than 4 cycles of immunotherapy. At the same time, our findings demonstrated that immunotherapy combined with nanoparticle albumin‐bound (nab-) paclitaxel-based regimens may prolong PFS (14.0 months vs 4.0months vs 2.5months, p = 0.0055) than gemcitabine-based regimens and other regimens. Conclusions: In patients with R/M HNC, the combination of immunotherapy and palliative radiotherapy demonstrates a synergistic effect, resulting in survival benefits. Prior radiotherapy might compromise patients’ PFS. Increasing the number of immunotherapy cycles and combining with nab-paclitaxel chemotherapy may improve patient survival.
Nuclear receptor subfamily 4A2: Novel role and a potential therapeutic lead in cancers.
Authors: Mudasir Ahmad Kumar, Aga Basit, Tariq Masoodi, Sanjib Chaudhary, Assif Assad, Muzafar Rasool Bhat, Zubair A. Shah, Ammira S. Al-Shabeeb Akil, Ajaz Ahmad Bhat, Surinder K. Batra, Muzafar Ahmad Macha
Journal: Journal of Clinical Oncology (2024)

e18017 Background: Perineural invasion (PNI) is a pathological process where cancer cells infiltrate surrounding nerve tissues, markedly increasing the risk of cancer recurrence, metastasis, post-surgical complications, and associated pain. Alarmingly, PNI is prevalent in 80 - 100% of Head and Neck Squamous Carcinoma (HNSCC) and Pancreatic Ductal Adenocarcinoma (PDAC) cases. In these tumors, nerve invasion often occurs as a distinct route of metastasis, bypassing the usual lymphatic or vascular routes. Despite the rigor of surgical interventions and post-operative radiation, PNI-associated tumors recurrently manifest, emphasizing an urgent need to elucidate the underlying molecular interplay between tumor cells and nerves. Methods: Our study focuses on the Nuclear receptor subfamily 4A2 (NR4A2) transcription factor, known for its pivotal roles in cellular homeostasis and response to pathological conditions. Results: Comprehensive analyses employing tissue microarrays, curated public datasets, and cell lines unveiled a consistent overexpression of NR4A2 in HNSCC and PDAC tumor cells compared to their normal counterparts. Intriguingly, genome-wide chromatin immunoprecipitation (ChIP) sequencing with an NR4A2-specific antibody highlighted an enrichment of genes linked to neuronal guidance, suggesting a probable NR4A2-mediated mechanism underpinning PNI. Further, an in-depth analysis of these ChIP-enriched neuronal genes using The Cancer Genome Atlas (TCGA) confirmed their heightened expression in HNSCC and PDAC tumor tissues relative to healthy tissues. Advancing our research with graph neural networks and sophisticated bioinformatics, we identified two potent lead compounds targeting NR4A2. Preliminary Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) assessments of these compounds indicate favorable safety and efficacy profiles for clinical application. We are currently conducting comprehensive evaluations of these compounds, deciphering their molecular mode of action and therapeutic potential in cell culture and animal models. Conclusions: To sum up, our findings reveal a yet unknown role of NR4A2 in the landscape of PNI in HNSCC and PDAC. The AI-driven discovery and ensuing validation of NR4A2-centric inhibitors present a novel therapeutic avenue to curb cancer progression, prevent metastasis, and potentially improve patient outcomes.
Economic evaluation of the novel PD-1 inhibitor toripalimab in recurrent or metastatic nasopharyngeal carcinoma: Cost-efficiency and expanded access modeling versus pembrolizumab.
Authors: Ivo Abraham, Marc Pondel, Karen MacDonald
Journal: Journal of Clinical Oncology (2024)

e18015 Background: Toripalimab, a novel anti-PD-1 antibody recently approved in the US as a breakthrough therapy in combination with gemcitabine and cisplatin (GemCis) for first-line treatment of adults with metastatic or recurrent locally advanced nasopharyngeal carcinoma (R/M NPC), is a category 1, NCCN-recommended preferred regimen. Although not FDA-approved for this indication, other PD-1 inhibitors, including pembrolizumab, are NCCN-recommended in combination with GemCis (category 2A but without direct evidence). The wholesale acquisition cost (WAC) of toripalimab at market entry is 80% that of pembrolizumab. This simulation modeling evaluates the cost-efficiency of toripalimab+GemCis versus pembrolizumab+GemCis in R/M NPC and the budget-neutral expanded access to the toripalimab regimen enabled by savings. Methods: Utilizing WAC drug costs and treatment administration costs, we modeled the cost-efficiency over a treatment duration equivalent to the toripalimab JUPITER-02 trial median PFS of 21.4 months (m). Without trial evidence for pembrolizumab+GemCis in R/M NPC, we assumed that such a regimen would be comparable to toripalimab+GemCis in median PFS. We also assumed that 31 cycles of PD-1 inhibitor (with GemCis in cycles 1-6) are administered over a median PFS of 21.4m. Using the cost-efficiency savings, we simulated the potential for budget-neutral expanded access to toripalimab treatment. A second model utilizing an ex ante toripalimab average sales price (ASP) of 80% of pembrolizumab ASP was estimated. Results: The WAC model estimated the toripalimab regimen to cost $292,316 (all agents over 21.4m or 31 cycles) while the pembrolizumab regimen costs $361,229, for savings of $68,913 per patient. These savings enable 7.7 additional toripalimab maintenance cycles to be purchased on a budget-neutral basis for every patient treated. For every 4.24 patients treated with toripalimab+GemCis instead of pembrolizumab+GemCis, one additional patient can be treated with the full toripalimab regimen (all agents) for 21.4m. Extrapolated to the 2024 US incident R/M NPC population of 1207 patients, if 50% of patients are treated with toripalimab+GemCis instead of pembrolizumab+GemCis savings of $41,589,183 provide access to 4,513 additional toripalimab maintenance cycles or 142 full toripalimab regimens (all agents for 21.4m) budget-neutrally. Similar results were demonstrated in the ASP model. Conclusions: With a market entry WAC that is 20% lower than pembrolizumab, toripalimab can generate approximate savings of $69,000 per patient over the median PFS treatment duration of 21.4m. If 50% of R/M NPC incident patients are treated with toripalimab, savings provide access to the full toripalimab+GemCis regimen to an additional 142 patients—effectively raising the treatment rate to 62% at no additional cost.
Utilizing stereotactic body radiation therapy in combination with tyrosine kinase inhibitors for therapeutic benefit in thyroid cancer.
Authors: Sundeep Kaur, Bin Gui, Maged Ghaly, Nagashree Seetharamu
Journal: Journal of Clinical Oncology (2024)

e18065 Background: Tyrosine kinase inhibitors improve overall survival (OS) and progression free survival (PFS) in metastatic thyroid cancer. Additionally, studies have shown success of hypo-fractionated radiotherapy in controlling local disease not responsive to systemic therapies. However, there is limited data assessing the combined benefits of radiation therapy (RT) and systemic therapy. This study aimed to determine the effects of adding radiation to tyrosine kinase inhibitors (TKIs) for symptomatic locoregional/metastatic iodine-refractory thyroid cancer. Methods: 21 patients with metastatic/loco-regionally advanced thyroid cancer were treated with radiation to areas of symptomatic disease alone or along with continuation of oral TKIs between March 2016 and December 2023. 18 were treated with RT + TKIs, while 3 were treated with RT only. Response to treatment was assessed 3 months post- RT treatment via imaging and clinical examination. The primary endpoint was assessing overall response rate as per RECIST 1.1. Secondary endpoints included local control, adverse effects, progression-free survival, and overall survival. Results: Median age of patients was 70. 12 patients were male, 14 patients had distant metastases. Histologic types include 12 papillary thyroid cancers, 4 anaplastic, and 5 others. 18 patients (85.7%) received treatment to thyroid mass, others were treated for nodal, soft tissue, and/or bone metastases. Most patients (90.5%) received stereotactic body radiation therapy (SBRT), while 2 patients received intensity-modulated radiation therapy (IMRT) due to insurance denial. The regimen that was frequently used (52.4%) was SBRT 800cGy in 5 fractions. 5 patients were treated with lenvatinib, 5 with dabrafenib/trametinib, and 4 with cabozantinib. 4 patients developed severe AEs requiring discontinuation or change in treatment plan. 74% of patients had documented response at 3 months post-treatment. 19 patients had additional follow up imaging and at median follow up of 16 months, 14 patients had continued clinical response with 9 complete responses (47.4%) and 5 partial responses (26.3%). The median duration of disease control at the site of RT was 23.4 months. Treatment was well-tolerated in general. 13/20 (65%) patients completed treatment without any interruptions or delays. Conclusions: SBRT can be effectively and safely administered to achieve durable disease control in patients with aggressive thyroid cancer histology when combined with tyrosine kinase inhibitors. This strategy warrants evaluation in prospective clinical trials.
Real-world effectiveness and safety of PD-1 inhibitors combined with recombinant human endostatin and chemotherapy in refractory, recurrent/metastatic nasopharyngeal carcinoma.
Authors: Shuang Huang, Caineng Cao, Mengyun Qiang, Yonghong Hua, Qifeng Jin, Ting Jin, Xiaozhong Chen
Journal: Journal of Clinical Oncology (2024)

e18007 Background: Nasopharyngeal carcinoma(NPC) is one of the most common head and neck malignancies with a high overall survival rate. However, the treatment of refractory, recurrent or metastatic NPC is complicated. This study aimed to evaluate the safety and effectiveness of GEP (Gemcitabine combined with recombinant human endostatin (Rh-endostatin) and anti-PD-1 antibody) in patients with refractory, recurrent or metastatic NPC that cannot be treated locally in the real-world setting. Methods: Patients with refractory, recurrent or metastatic NPC (Refractory patients were defined as those unsuitable for local treatment due to extensive tumor recurrence/metastasis or necrosis of ulcers) treated in our hospital from December 2022 to October 2023 were retrospectively reviewed and analyzed. with the GEP regimen. Patients received 1-6 cycles of GEP therapy, including Gemcitabine (1.0 g /m 2 ond1 and d8) combined with Rh-endostatin (180-210 mg/continuous intravenous pump 72-120h) and PD-1 antibody, Objective response rate (ORR) and disease control rate (DCR) were determined by Clopper-Pearson's method. The incidence of adverse events (AES). Results: A total of 25 patients who completed ≥ 2 cycles of treatment and at least one efficacy assessment were included in the efficacy analysis. The median age was 59 years (range: 33-75 years), 36% of patients ≥ 65 years. There was significant liquefaction necrosis in 17 cases (68%). 68% of the patients were treated with second-line or above GEP. 32% (8/25) of patients had tumor progression after anti-vascular therapy, and 44% (11/25) had disease progression after immunotherapy. Based on RECIST 1.1, the ORR was 44.00% (95%CI: 26.67%, 62.93%), and DCR was 92.00% (95%CI: 70.04%, 95.83%). The history of immunotherapy was a significant influence factor on ORR. 30 patients who received at least one course of GEP therapy were included in the safety analysis. Grade 3 AEs were observed in 7 patients (20%), with hematological toxicity (6/7) and hypertension (1/7). Other AEs with more than 20% incidence were hematological toxicity (93.0%), weight loss (67.0%), abdominal distension and constipation (47.0%), hypertension (47%), infection (33.0%), liver dysfunction (27.0%), nausea and vomiting (23.0%), and infusion reaction (20.0%). The recurrent lesions of 15 patients with recurrent NPC were accompanied by significant liquefaction necrosis and ulcers. The ORR was 46.7%, and DCR was 100%. Among them, 5 patients had grade 1 nosebleed, and the other grade 2 or above AEs were hematological toxicity, and there were no grade 4 treatment-related AEs. Conclusions: Real-world data demonstrated that GEP was well-tolerated, safe and effective in patients with refractory, recurrent or metastatic NPC.
Comparative efficacy of pembrolizumab with carboplatin and paclitaxel as first-line (1L) therapy in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC): A network meta-analysis (NMA) with matching-adjusted indirect comparison (MAIC).
Authors: Dandan Zheng, Ali Mojebi, Christopher M. Black, Hilde Giezek, Niroshini Naicker, Chiara Vanetta, Sam Keeping, Sanjay Merchant, Marcin Radoslaw Dzienis
Journal: Journal of Clinical Oncology (2024)

e18006 Background: The single-arm, phase IV, KEYNOTE-B10 (KNB10) trial demonstrated the antitumor effect of the KNB10 regimen for 1L treatment of R/M HNSCC. It is critical to understand the comparative efficacy of the KNB10 regimen versus other recommended interventions in 1L R/M HNSCC, using advanced evidence synthesis methodologies, to inform clinical decision making. Methods: A systematic literature review, conducted on October 31, 2023, identified 25 randomized controlled trials evaluating 1L interventions in R/M HNSCC, of which six evaluated recommended interventions and formed a connected network. Of these, KEYNOTE-048 was determined to be the most similar study to the disconnected, single-arm, KEYNOTE-B10 trial. Therefore, individual patient-level data from KEYNOTE-B10 final analysis were reweighted and matched to KEYNOTE-048 via a MAIC in terms of metastatic disease, PD-L1 Combined Positive Score, ECOG performance status, primary tumor location as well as HPV status, sex, race, age, and smoking status. KEYNOTE-B10 was then considered an additional treatment arm of KEYNOTE-048 and was incorporated in the network. Fixed-effect NMA models in Bayesian framework were then used to estimate odds ratios of objective response rate (ORR), with 95% credible intervals, for comparisons between KNB10 and other interventions recommended for 1L R/M HNSCC. Results: Results from the fixed-effects NMA are summarized in the table. For ORR, the KNB10 regimen was more efficacious compared to pembrolizumab+platinum+5-FU, cetuximab+platinum+5-FU, platinum+5-FU, cisplatin+paclitaxel, cisplatin, 5-FU, and methotrexate ( p &lt; 0.05). There was no statistically significant difference in ORR between the KNB10 regimen and cetuximab+cisplatin+docetaxel. Conclusions: This NMA with MAIC suggests patients treated with the KNB10 regimen had improved or comparable ORR outcomes versus other recommended 1L interventions for R/M HNSCC, which further reinforces the combination therapy of pembrolizumab+platinum+taxane as an acceptable alternative 1L treatment option for R/M HNSCC. Future analyses should additionally compare survival outcomes between the KNB10 regimen and other recognized interventions in this patient population. [Table: see text]
Epidemiological analysis and overall survival of thyroid cancer in a developing Middle Eastern Country over 18 years.
Authors: Zaid A. Abdulelah, Ahmed A. Abdulelah, Abdulrahman Ahmad Alhajahjeh, Mohammad Al-Dqour, Aseel Saadeh, Hikmat Abdel-Razeq
Journal: Journal of Clinical Oncology (2024)

e18071 Background: The significance of thyroid cancer lies not only in the resulting morbidity and mortality, but in its prevalence as the most commonly encountered endocrine malignancy in the Middle East and globally. Given that thyroid cancer epidemiology in the Middle East is not sufficiently evaluated, the establishment of epidemiological characteristics of thyroid cancer in the Middle Eastern population is of substantial importance for the introduction of effective interventions, especially in scarcely resourced countries and populations. Methods: Comprehensive data on 4,362 patients of various nationalities residing in Jordan diagnosed with thyroid cancer during the period 2000-2018 were retrieved from the Jordan Cancer Registry, the official institutionalized reporting body for cancer epidemiology in Jordan. Epidemiological analysis including Kaplan-Meier analysis and regression models was performed to establish the epidemiological features of thyroid cancer in a Middle Eastern population. Results: A total of 4,362 patients with a mean age of 43.5 ± 29.6 years old and a significant female predominance of 74.9% were included in the analysis. 7.97% of the enrolled patients were smokers at the time of diagnosis. Thyroid carcinoma was found in the right and left thyroid lobes almost equally the same, with only 1.28% having involvement in both lobes. Localized thyroid carcinoma was encountered in 28.8% of the sample, while 6.65% had systemic involvement and distant metastasis. The observed overall survival rate was determined to be 94.7%, 94.7%, 94.1%, 88.2%, and 86.6% at 1-year, 2-year, 3-year, 4-year, and 5-year interval, respectively. There is a statistically significant incline in the crude incidence of thyroid cancer in Jordan over the 18 years with a crude incidence estimated effect of 0.19 (P-value&lt;0.001). Conclusions: Over 18 years, thyroid cancer in Jordan has been progressively increasing in incidence with a worrisome uptrend that carries significant socioeconomic and health burden. Ensuring preventative measures such as reduced exposure to radiation and early detection of thyroid nodules are warranted to achieve better outcomes.
Prevalence and risk factors associated with chronic pain among survivors of head and neck cancer.
Authors: Rong Jiang, Meng Chen, Melissa Christina White, Katherine Ramos, Cheyenne Corbett, Tammara L Watts, Evan Michael Graboyes, Nosayaba Osazuwa-Peters
Journal: Journal of Clinical Oncology (2024)

e18016 Background: There are over 500,000 survivors of head and neck cancer (HNC) in the United States. Pain is one of the most common symptoms of HNC due to disease anatomy, treatment and post-treatment toxicities. While opioid treatment is a mainstay in HNC care, factors associated with chronic pain are not properly understood. Methods: We built a retrospective cohort of adult patients with a history of HNC using the National Health Interview Survey (NHIS) from 2010 to 2021 that collected through personal household interviews ( n = 353). Chronic pain was defined using the question: In the past three months, how often did you have pain? Would you say never, some days, most days, or every day? Chronic pain was coded as “yes” if the response was most or every day, and “no” if it was never or some days. Using weighted logistic regression analysis adjusting for age and sex, we examined the association between chronic pain and sociodemographic (race, insurance, education, income, employment and smoking history) and clinical (depression, and self-rated health status) factors. Results: Among individuals with a history of HNC, 149 (adjusted Prevalence Rate = 43.2%; 95% CI: 36.6%, 49.8%) had experienced chronic pain in the past three months. There were significant associations with clinical factors, as individuals with poor self-rated health (aOR = 6.42; 95% CI: 3.25, 12.70) and those with depression (aOR = 3.25; 95% CI: 1.73, 6.11) had increased odds of reporting chronic pain. Among sociodemographic factors White race (aOR = 2.52, 95% CI: 1.04, 6.10) and Medicaid insurance (aOR = 3.76, 95% CI: 1.40, 10.10) were associated with and increased odds of reporting chronic pain. There was no significant association of education, income, employment or smoking history with chronic pain among the study HNC survivors. Conclusions: Over 40% of individuals with a history of HNC may be living with chronic pain, unequally distributed based on race, payor status and comorbid depression. Given the current opioid crisis in the United States, and the poor outcomes associated mental health in cancer survivors, our findings highlight clinical and social determinants of health factors that should be taken into the consideration for management of chronic pain among survivors of HNC patients.