tbuckley/cabot-search huggingface dataset:
Induction chemotherapy effects on very advanced (T3/T4) human papillomavirus-related oropharyngeal cancer for participation in hypoxia-directed major de-escalation (30 Gy) definitive treatment trial.
Authors: Eric Jeffrey Sherman, Nadeem Riaz, Lara Dunn, Heiko Schöder, Rick Wray, Ian Ganly, Jay Boyle, Snehal G. Patel, Babak Givi, James Vincent Fetten, Winston Wong, Tony Hung, Anuja Kriplani, Kaveh Zakeri, Daphna Y. Gelblum, Yao Yu, Linda Chen, Achraf Shamseddine, Richard J. Wong, NANCY Y. LEE
Journal: Journal of Clinical Oncology (2024)

6076 Background: De-escalation trials in human papillomavirus associated oropharyngeal carcinoma (HPV+ OPC) often exclude patients with very locally advanced disease. We previously demonstrated in a Phase II study that for patients with T1-T2 HPV+OPC that de-escalation to 30Gy of definitive chemoradiation based on lack of hypoxia on 18 F-FMISO (fluoromisonidazole) PET (ROC Study) is associated with excellent outcomes (JNCI 2021; JCO 2024). Here, we hypothesized that induction chemotherapy (ICT) could be used in locally advanced (T3-T4) HPV+OPC to down-stage patients and make them eligible for de-escalation and simultaneously improve tumor hypoxia. Methods: We conducted a pilot study in HPV+ OPC patients with AJCC v7 T3-T4 and/or large volume N2b-N2c-N3 disease (i.e. pts ineligible for ROC Study (NCT03323563)). ICT – carboplatin (AUC2), paclitaxel (90 mg/m2), and cetuximab (250 mg/m2 after 400 mg/m2 loading dose) weekly for 6 weeks. To be eligible for de-escalation (ROC), after ICT, patients needed to be down-staged (&lt;=T2). 18 F-FMISO PET scan done prior to ICT, after ICT, and, if eligible for ROC study, about 2 weeks after start of radiation therapy. If an 18 F-FMISO PET scan showed no hypoxia at any time point, no further scans necessary and patients received 30Gy of radiation therapy with 2 cycles of chemotherapy concurrently. Primary outcome is 2-year local control rate in 20 evaluable patients (description only in this pilot study). This abstract reports only on the outcomes of the ICT portion of the study. Results: 20 patients were accrued 3/2023-12/2023. Median age - 70 years old (46-88); Male – 95%; ECOG PS 0 – 80%. Tumor stage – T3 (70%); T4a (30%); N2b (70%); N2c (30%). All 20 patients had pretreatment hypoxia by 18 F-FMISO. Of the 17 evaluable patients post ICT, 14 (82%) had no hypoxia on post ICT scan (other 3 still receiving ICT). Of 3 patients with hypoxia after ICT, 2 had resolution 2 weeks into radiotherapy, and 1 patient is still pending intra-treatment scan. All 17 evaluable patients had a significant enough of a response anatomically to allow treatment on the ROC Study. All patients to date were able to receive 2 cycles of cisplatin (100 mg/m2) without dose or treatment adjustment. Conclusions: Preliminary results suggest that ICT can allow more advanced tumors (T3/T4), that are typically excluded from de-escalation studies, to be de-escalated and may eliminate tumor hypoxia in a large proportion of cases, but a larger study is needed to confirm these results. Further followup of outcomes (2 year local control rate) is still needed. Clinical trial information: NCT05491512 .
Evaluating perceived barriers to optimal care in head and neck cancer: A mixed-methods study.
Authors: Steven Francis Powell, Beth Michelle Beadle, Tammara L Watts, Jessica H. Maxwell, Linda Hutkin-Slade, Hilda Haynes-Lewis, Kimberly Demirhan, Elana Plotkin, Angie Rush, Jacqueline Dibble, Joseph Kim
Journal: Journal of Clinical Oncology (2024)

6079 Background: Head and neck cancer (HNC) is a complex disease that requires multidisciplinary care and poses significant challenges for patients and healthcare providers. Despite the availability of evidence-based guidelines, achieving optimal HNC care faces many barriers. This mixed-methods study explores the perceived barriers by patients and clinicians to optimal HNC care. Methods: The Association of Cancer Care Centers (ACCC) collaborated with the Head and Neck Cancer Alliance and the American Society for Radiation Oncology (ASTRO), along with an expert steering committee of multidisciplinary roles representing diverse cancer care centers, to evaluate the current landscape of HNC care delivery. Using an explanatory sequential design, ACCC conducted patient (n= 247) and provider (n=206) surveys and four focus groups which included patients with HNC and clinicians to capture barriers to optimal HNC care. Results: Barriers were classified as patient-related, provider-related, and system-related factors. Survey highlights include: 32% of patients received multimodal treatment including surgery, radiation, and medications; 50% of clinicians were at centers that utilized multidisciplinary clinics for HNC; 60% of patients “strongly agreed” they were satisfied with their care; 48% of patients felt members of their treatment team communicated and coordinated care “very well”; and 56% of patients “strongly agreed” clinicians explained their diagnosis comprehensibly. Clinicians and patients differed in their perspectives on how care was delivered in a few areas: 52% of clinicians vs. 40% of patients agreed that side effects of treatment were explained in ways that patients could understand; 29% of clinicians vs. 21% of patients felt that emotional concerns and mental health needs were addressed. Clinicians identified key areas that needed improvement to provide more effective care: financial resources (62%), dedicated navigation (45%), and coordination across members of the care team (45%). Qualitative analysis of focus group responses identified travel logistics to care centers, inadequate health insurance coverage, and lack of dental insurance delaying care as major systems-related barriers to optimal HNC care. Conclusions: This study revealed insights into the delivery of optimal care in HNC in the US, including being a high-volume center, having dedicated HNC nurse navigators, and multidisciplinary meetings for care coordination. Multifactorial barriers to optimal HNC care were also identified and will be used to inform future educational programming and the development of interventions to improve care.
Patients with radioiodine-refractory differentiated thyroid cancer (RAI-R DTC) with BRAF V600E and/or K601E mutation status: A real-world view of effectiveness of lenvatinib monotherapy.
Authors: Francis P. Worden, Lori J. Wirth, Neil Reynolds, Charley Cooper, Olivera Rajkovic-Hooley, Gary Milligan, Phananh Pham, Hakim Saal, Marcia S. Brose
Journal: Journal of Clinical Oncology (2024)

6098 Background: Lenvatinib was approved for the treatment of patients RAI-R DTC in the United States (US) in 2015, and the treatment landscape has evolved with agents targeting specific driver mutations. We assessed real-world clinical effectiveness of first line therapy with lenvatinib in patients with BRAF-mutated tumors, wild-type (WT) tumors, and patients who have not been tested for BRAF mutations (BRAF untested tumors). Methods: A retrospective chart review of RAI-R DTC patients in the US who initiated first-line lenvatinib monotherapy between February 13, 2015, and September 30, 2020. Data, including a boosted cohort of patients with BRAF-mutated tumors collected in late 2023, were abstracted from patients’ electronic health records and were de-identified. Descriptive analyses were conducted in patient cohorts with BRAF V600E and/or K601E mutated tumors, wild-type (WT) tumors, and BRAF untested tumors. Best response in first-line therapy was captured, real-world progression-free survival (rwPFS) and real-world overall survival (rwOS) were assessed using Kaplan-Meier methods. Results: Of the 361 patients reviewed, 185 had records showing BRAF mutational status testing. 89 had BRAF V600E and/or K601E mutated tumors, 96 had WT tumors. 176 patients did not have BRAF mutational assessment. Of all subjects, 73.7% were White/Caucasian, 15.2% were African American, and 16.8% were Hispanic/Latino; 27.1% had ECOG performance status ≥2. The median follow-up times for each cohort were 30.0, 18.7 and 18.0 months, showing the longer follow up period for the BRAF-mutated cohort boost. Kaplan-Meier estimation for lenvatinib treatment discontinuation for the three cohorts at 24-months were as shown in the table below. Provider-reported overall response rate (complete or partial response) was 76.4%, 75.0% and 69.3% respectively. The estimated 24-month rwPFS rates (95% CI) were 74.1% (62.2%-82.8%), 61.7% (49.6%-71.8%), and 69.8% (60.9%-77.0%) respectively. Median rwOS was not reached for patients with BRAF-mutated and WT tumors, median OS was 54.2 months for BRAF untested tumors. Estimated rwOS rates at 12- and 48-months were 93.2% (85.4%-96.9%) and 83.9% (73.3%-90.3%) in BRAF-mutated patients, 90.6% (82.8%-95.0%) and 68.5% (53.4%-79.6%) in WT patients, and 90.2% (84.7%-93.8%) and 72.5% (61.6%-80.7%) in BRAF untested patients respectively. Conclusions: In this US real-world experience, the effectiveness of lenvatinib is consistent across a diverse cohort of RAI-R DTC patients with BRAF-mutated, WT, and BRAF untested tumors. This has implications for the first-line use of lenvatinib in BRAF mutated patients. [Table: see text]
Mapping the mental health correlates of head and neck cancer: A systemic review and meta-analysis.
Authors: Pablo Jiménez Labaig, Claudia Aymerich, Antonio Rullan, Sandra Llop, Irene Brana, Jon Cacicedo, Kevin Joseph Harrington, Ana Catalan
Journal: Journal of Clinical Oncology (2024)

6077 Background: Patients with head and neck cancer (HNC) present particularly high levels of mental health disorders. Yet the actual rate of relevant mental health symptoms and disorders, along with its determinants, remains unclear. Methods: A PRISMA/MOOSE-compliant systematic review and quantitative effects meta-analysis (PROSPERO: CRD42023441432) was conducted to determine the prevalence of depression, anxiety, distress, post-traumatic stress, insomnia and suicide among patients with HNC. MEDLINE, WebofScience, Cochrane Central Register, KCI-Korean Journal, SciELO, Russian Science Citation Index and Ovid/PsycINFO databases were searched from database inception to August 1, 2023. Secondary analyses were used to assess longitudinal trajectories of the samples over time. Results: 208 studies (n=713,527, median age 60.7; 25.5% female) were included. 19.5% patients reported depressive symptoms (95% confidence interval [CI]=17-21%), 17.8% anxiety symptoms (95%CI=14-21%), 34.3% distress (95%CI=29-39%), 17.7% post-traumatic symptoms (95%CI=6-41%) and 43.8% insomnia symptoms (95%CI=35-52%). Diagnostic criteria assessments revealed lower prevalence of disorders: 10.3% depression (95%CI=7-13%), 5.6% anxiety (95%CI=2-10%), 9.6% insomnia (95%CI=1-40%), and 1% post-traumatic stress (95%CI=0-84.5%). Pooled suicide incidence was 161.16 per 100,000 individuals per year (95%CI=82-239). A higher prevalence of anxiety was found in patients undergoing primary chemoradiation compared to surgery, and increased distress in smokers and advanced tumor staging. European samples exhibited lower prevalence of distress. Patients were more likely to be depressed after finishing radiation treatment. Conclusions: Patients with HNC exhibited a notable prevalence of mental health issues across various domains, where suicide emerged as a particular concern. There is a need for improved methods of assessment and intervention for these mental health concerns. Preventive interventions should be implemented before the start of radiation treatments. [Table: see text]
Neoadjuvant tislelizumab with afatinib for locally advanced head and neck squamous cell carcinoma (neoCHANCE-1): An open-label, single-arm, phase 2 study.
Authors: Zhigong Wei, Huijiao Chen, Lei Cai, Fei Chen, Jun Liu, Xingchen Peng
Journal: Journal of Clinical Oncology (2024)

6073 Background: For patients with locally advanced head and neck squamous cell carcinoma (HNSCC), even receiving surgery with adjuvant radiotherapy or chemoradiotherapy, those remain at high risk of recurrence or metastasis. Neoadjuvant immunotherapy has been used in HNSCC, but provides only modest pathological response. Given single agent activity and unique mechanism of action of immune checkpoint inhibitors and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), we aimed to evaluate the antitumour activity and safety of neoadjuvant PD-1 blockade with EGFR inhibition in locally advanced HNSCC. Methods: This open-label, single-arm, phase 2 trial was done at a a tertiary hospital in China. Eligible patients were aged 18 years or older and had resectable HNSCC disease, had an Eastern Cooperative Oncology Group performance status of 0–1, had at least one measurable target lesion according to the RECIST 1.1, had no prior antitumor therapy for HNSCC. Patients received neoadjuvant treatment with intravenous tislelizumab (200 mg) on the first day of each 3 week, with totally two cycles and orally afatinib (30 mg) starting on the first treatment day and ending on the day before surgery, with totally six weeks, and then patients proceeded to receive surgical resection. The primary endpoint was major pathological response, defined as the presence of 10% or less residual viable tumour at the time of surgery. Results: A total of 25 patients were enrolled completed the neoadjuvant therapy. Eight of 23 evaluable patients exhibited a major pathological response (MPR) (35%; 95% confidence interval [CI], 16%—57%), of which four had a complete pathological response of primary tumor (17%, 95%CI, 5%—39%). The overall response rate was 48% (12/25, 95%CI: 28%—69%) and disease control rate was 100% (25/25, 95%CI: 86%—100%). Common grade 3—4 adverse events included diarrhea (5/25 [20%]), hypokalemia (4/25 [16%]) and rash (3/25 [12%]). No treatment related fatalities were observed. Immunologically, post-neoadjuvant treatment demonstrated increased CD3, CD8, and CD56 expression within the tumor microenvironment. The increase of CD8 and CD56 expression level was significant higher in patients achieving MPR, along with elevated circulatory NK cells at baseline, compared to those in patients achieving non-MPR. Conclusions: This study underscores encouraging antitumor activity, manageable toxicity profile and promising immune activation elicited by neoadjuvant tislelizumab plus afatinib for HNSCC, which deserves further assessment. Clinical trial information: NCT05517330 .
A prospective multicenter trial of dose escalation for weekly gemcitabine concurrent with intensity-modulated radiotherapy following cisplatin and gemcitabine induction chemotherapy in patients with locally advanced nasopharyngeal carcinoma.
Authors: Zeng Qi, Bingqin Lin, Fangming Li, Yumeng Liu, Siyang Wang, Feiqiang Deng, Shaona Lei
Journal: Journal of Clinical Oncology (2024)

6071 Background: Gemcitabine and cisplatin induction chemotherapy, followed by cisplatin-based concurrent chemoradiotherapy, constitutes the standard treatment for locally advanced nasopharyngeal carcinoma (LANPC). However, the substantial cumulative dosage of cisplatin used in this approach renders it intolerable for many patients due to advanced age or compromised renal function. Therefore, identifying alternative chemotherapeutic agents is crucial. Gemcitabine is a potent radiosensitizer with an overall favorable safety profile. Despite extensive research on the maximum tolerated dose (MTD) of concurrent gemcitabine chemotherapy in head and neck cancer, its MTD as a single-agent chemotherapy concurrently administered with intensity-modulated radiotherapy (IMRT) in LANPC remains uncertain. Methods: Patients diagnosed with stage III-IVa nasopharyngeal carcinoma were prospectively enrolled in three hospitals located within the largest NPC endemic area in southern China. After two cycles of cisplatin plus gemcitabine induction chemotherapy, patients underwent combined concurrent radiochemotherapy (70 Gy/6-7 weeks) with weekly gemcitabine. The initial dose level was set at 25mg/m 2 and subsequently escalated in a sequential manner to higher doses of 50mg/m 2 , 100mg/m 2 , 200mg/m 2 , and 300mg/m 2 etc. Our study employed a dose escalation strategy in which the dosage was incremented to the next group only if no more than one out of six patients experienced Dose-Limiting Toxicity (DLT), until DLT occurred in at least two patients. Patients underwent follow-up evaluations every three months. This study is registered with ClinicalTrials.gov under NCT04522050. Results: Between October 2018 and December 2023, a total of 39 Chinese patients were enrolled, 36 (27 males, 9 females) patients were considered evaluable. The incidence of DLT was observed in two out of six patients receiving a dosage level of 300 mg/m², with both cases presenting Grade 3 oral mucositis. Subsequently, the study was replicated using the same dosage level, resulting again in two instances of DLT: one case with Grade 3 radiation dermatitis and another case with oral mucositis. Consequently, a reduced dosage level of 200mg/m² was determined as MTD. No significant hematological toxicity or serious gastrointestinal adverse events were observed. Tumor response evaluation by MRI after twelve weeks of IMRT showed a complete response rate of 100%. To date, only two cases (5.56%) have been reported exhibiting tumor recurrence. Conclusions: The MTD for weekly gemcitabine with IMRT following induction chemotherapy in LANPC is determined to be 200 mg/m 2 . The DLT associated with this treatment regimen primarily consists of radiation dermatitis and/or oral mucositis. Clinical trial information: NCT04522050 .
Analysis of PD-L1 expression in locally advanced head and neck squamous cell carcinoma and its correlation with the efficacy of neoadjuvant immunotherapy + chemotherapy: A retrospective real-world study.
Authors: Haolei Tan, Wenxiao Huang, Ying Long, Hailin Zhang, Waisheng Zhong, Pingqing Tan, Yaqian Han, Feng Liu, Cuihong Jiang, Jinyun Li, Yujuan Zhou, Zheng Wu
Journal: Journal of Clinical Oncology (2024)

6074 Background: The incidence rate of HNSCC in Hunan China are notably higher than in other regions, likely due to the high prevalence of betel nut chewing. Therefore, we conducted a study to examine the PD-L1 expression in newly diagnosed locally advanced (stage III-IVB) HNSCC patients. Methods: 1. We conducted a retrospective analysis of the PD-L1 expression (represented as CPS) in pre-treatment biopsy tissues from locally advanced HNSCC. 2. 57 patients received neoadjuvant treatment consisting of nab-paclitaxel+ cisplatin+ pembrolizumab. The efficacy of the treatment was evaluated using pathology assessments. Results: 1. A total of 373 patients were included. The top five primary sites of the tumors were the tongue(32.17%), Buccal oris (20.91%), oropharynx (10.19%), hypopharynx(9.92%), and gingiva(7.77%). The proportion of patients with PD-L1 CPS≥20 (55.23%) was significantly higher than the 43.20% reported in the KEYNOTE-048 study. Furthermore, the subgroup was even higher in the buccal oris (70.51%) and gingiva (72.41%). 2. A total of 57 patients were tested for PD-L1 CPS and received neoadjuvant treatment.After surgery, 22/57 (38.60%) achieved pathological complete response (pCR) or major pathological response (MPR), 29/57 (50.88%) achieved partial pathological response (pPR), resulting in an overall response rate (ORR) of 89.47%. In the PD-L1 CPS ≥20 group, the ORR was as high as 91.89% (34/37). 3. Among the 57 patients, 36 patients had lymph node metastasis. After treatment, 15/36 patients (41.67%) achieved pCR/MPR in lymph nodes, 7/36 patients (19.44%) achieved pPR, resulting in an ORR was 61.11% (22/36). Conclusions: 1. The oral cavity is the most common primary in HNSCC in Hunan,China. In the locally advanced , the proportion of PD-L1 CPS ≥20 is higher than reported in other studies. 2. Regardless of PD-L1 expression, neoadjuvant treatment with nab-paclitaxel+ cisplatin+ pembrolizumab has shown a high rate of local disease control in newly diagnosed HNSCC patients. Additionally, the use of neoadjuvant therapy has improved the delineation of surgical safety margins, leading to 100% R0 resections in all 57 patients. 3. The response of the primary lesion in patients treated with neoadjuvant therapy is better than that of the lymph node. Patients with a well-responding primary lesion but multiple lymph node metastases should be closely monitored for the possibility of short-term systemic metastasis. [Table: see text]
GI snapshot: arrhythmia, dysphagia and weight loss in a 71-year-old man
Authors: Martina De Siena, Loredana Gualtieri, Simone Varca, Maria Valeria Matteo, Valerio Pontecorvi, Vincenzo Bove, Cristiano Spada, Ivo Boškoski
Journal: Gut (2024)
Prospective validation of ctHPVDNA for detection of minimal residual disease and prediction of recurrence in patients with HPV-associated head and neck cancer treated with surgery.
Authors: Shun Hirayama, Yana Al-Inaya, Ling Aye, Michael E. Bryan, Dipon Das, Julia Mendel, Saskia Naegele, William C Faquin, Peter Sadow, Adam S. Fisch, Derrick Lin, Mark A Varvares, Allen Feng, Kevin S. Emerick, Daniel G. Deschler, Michael S. Lawrence, A. John Iafrate, Annie Chan, Jeremy Richmon, Daniel Faden
Journal: Journal of Clinical Oncology (2024)

6010 Background: Prediction of minimal residual disease (MRD) following surgery, and thus the need for adjuvant therapy, is currently based on clinicopathologic risk factors which have poor individual prognostic capacity. We previously reported that MRD detection by ctHPVDNA droplet digital (dd)PCR as early as post-operative day (POD) 1 is predictive of recurrence in stage I-II HPV+HNSCC patients. Here, we applied a significantly more sensitive custom whole genome hybrid-capture-based next generation sequencing assay, termed HPV-DeepSeek, to validate the prognostic capacity of ctHPVDNA detection and explore the optimal timing of MRD testing in HPV+HNSCC patients. We tested the primary hypothesis that patients with MRD detection within 6 weeks of surgery would have inferior PFS at 2 years and the secondary hypothesis that patients with ctHPVDNA positivity detected at any point following treatment completion would have inferior PFS at 2 years. Methods: 98 patients with HPV+HNSCC were prospectively enrolled with a mean follow-up of 712 days. All patients underwent surgery as primary treatment and clinicopathologic adjusted adjuvant treatment. 10ml blood samples were collected before surgery, in the post-operative period (POD 1-42), and serially in follow-up. MRD was defined as a lack of ctHPVDNA clearance during the 6 weeks following surgery. Cell free DNA was extracted from plasma and run on HPV-DeepSeek, and on existing ddPCR assays for head to head comparisons. Results: 96/98 (98%) of patients had detectable ctHPVDNA pre-treatment. 30/98 patients (31%) were MRD positive. Patients who were MRD positive had significantly worse 2 years PFS compared to MRD negative patients (78% vs 98%, P=0.0009). Predictive performance improved by limiting time points to POD 7-42 (2 year PFS 60% vs 97%, P&lt;0.0001) as significantly fewer patients were MRD positive &gt;1 week after surgery, suggesting the use of an ultra-sensitive assay such as HPV-DeepSeek requires adjustment of MRD time points. Patients with detectable ctHPVDNA following completion of all treatment had significantly worse 2-year PFS compared to patients without detectable ctHPVDNA (0% vs 97%, P&lt;0.0001). 7/98 patients had cancer recurrence during follow-up that was detected by ctHPVDNA with a mean lead time of 207 days (35-518) to clinical diagnosis. Conclusions: ctHPVDNA detection by HPV-DeepSeek is a highly specific biomarker of MRD in HPV+HNSCC, accurately predicts disease progression and detects recurrence earlier than standard care clinical.