bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real world evidence for use of NACT in locally advanced external auditory canal cancer.
Authors: Rai Rahul Kumar , Patil Vijay Maruti , Noronha Vanita , Menon Nandini Sharrel , Saha Saswata , Alone Mitali , Pai P. S. , Laskar Sarbani , Prabhash Kumar 
Published: June 2022

e18000 Background: The management of very locally advanced external auditory canal cancers (LAEACC) is complicated, has a dismal prognosis and there is limited literature available for guidance. At our institute, we have offered neoadjuvant chemotherapy (NACT) to such patients. The objective of the current analysis was to study the outcomes and adverse events with this approach. Methods: We identified 16 patients with LAEACC over a period of 10 years (2010-2020) from the neoadjuvant chemotherapy (NACT) database of the Head and Neck department at our hospital. All patients were seen in a multidisciplinary clinic before and after NACT. Further local therapy was planned as per the response and ECOG PS of the patient. SPSS version 20 was used for analysis. Descriptive statistics were performed and Kaplan-Meier analysis was done to evaluate overall survival and progression-free survival. Results: Out of 16 patients enrolled in the study, 14 patients eventually received NACT. The median age was 59.5 years (27 - 83), the male to female ratio was 7:1 and the ECOG PS was 0-1 in 14 (87.5%) and PS 2 in rest. The regimen offered was a 2 drug regimen of taxane and platinum in 11 patients and a 3 drug regimen of TPF in (7.14%) patients. The median cycle received was 2. Post NACT 6 (42.85%) patients underwent surgery, 5 (35.71%) received radical CTRT and 3 (21.42%) patients received palliative treatment. The median progression-free survival was 1.67 years [95% CI (0.364 - 6.175)] while the median overall survival was 2.0 years [95% CI (0.455 - 6.175)]. Conclusions: Locally advanced EACC where upfront surgery is not feasible, NACT can be considered an option as patients receiving NACT have a 44.44% response rate and surgical resection rate of 42.8%.
Clinical utility of circulating tumor DNA in patients with head and neck cancers.
Authors: Onyshchenko Mykola , Rock Adam , Sila Chad , LaBarbera Katie , Rathore Richa , Ji Ping , McPhaul Laron 
Published: June 2022

e18003 Background: Globally, head and neck cancers (HNCs) account for over 900,000 cases annually with a meager overall survival rate of 50%. While early-stage HNCs may be amenable to surgery, advanced disease is treated with systemic therapy or chemoradiation. For localized disease, chemo-radiation is often curative, but is associated with severe toxicity. Assessment of systemic treatment in the era of immunotherapy is often challenging due to the pseudoprogression phenomenon. In general, surveillance is limited to clinical follow-up and radiological imaging due to the lack of a sensitive and specific biomarker to assess treatment response and disease progression. Circulating tumor DNA (ctDNA) has shown promise as a reliable marker of disease activity in several solid tumors. In this study we evaluated the clinical utility of ctDNA for monitoring of therapeutic response and disease progression in patients with HNCs. Methods: ctDNA analysis was performed utilizing a personalized, tumor-informed ctDNA assay (Signatera™ bespoke mPCR NGS assay) in patients with advanced stage (III, IV) HNC who underwent chemoradiation or systemic therapy. ctDNA levels were measured at diagnosis, throughout treatment and during remission. The primary endpoint was correlation of ctDNA kinetics with radiological response. The secondary endpoint was the rate of ctDNA positivity during remission. Additional data collected included patient demographics and tumor clinicopathologic characteristics. Analysis was conducted using descriptive statistics. Results: ctDNA kinetics from 15 patients with squamous HNCs were analyzed. Due to insufficient time points, 5 five patients were excluded from this analysis. At diagnosis, 9/10 (90%) patients were ctDNA-positive, with baseline ctDNA levels ranging from 0.2 to 8500 mean tumor molecules (MTM)/mL of plasma. Patients received either chemoradiation (7/10) or (chemo)immunotherapy (3/10). Among patients who received chemoradiation, 4 out of 7 cleared ctDNA in less than 40 days, while 2 out of 7 had persistent ctDNA after 40 days. Those who showed ctDNA clearance had a continued response at 3-6 month follow-up both by ctDNA and by standard of care imaging. The 2 patients that did not clear ctDNA by day 40 ultimately relapsed on imaging and had rising ctDNA levels within 3 months of completion of chemoradiation. The patient who was ctDNA negative at baseline remained negative throughout the treatment and follow up. Of the patients who received chemo(immunotherapy), 2/3 cleared ctDNA after 2 cycles of therapy and continued to be in remission. The remaining patient who did not show ctDNA clearance became refractory to treatment. Conclusions: Our study demonstrates the feasibility of personalized and tumor-informed ctDNA in patients with advanced HNCs. Monitoring of ctDNA kinetics during therapy may enable prediction of therapeutic response and early disease progression to guide clinical decision-making.
Real-world time on treatment analysis of pembrolizumab treated recurrent/metastatic head & neck squamous cell carcinoma (R/M HNSCC) patients stratified by ECOG PS in the United States.
Authors: Black Christopher Matthew , Wang Liya , Ramakrishnan Karthik , Turzhitsky Vladimir 
Published: June 2022

e18007 Background: There is limited evidence on the real-world use of pembrolizumab therapy post-approval in 1L R/M HNSCC. The study estimated real-world time on treatment (rwToT) of pembrolizumab monotherapy and pembrolizumab + platinum + 5FU for 1L R/M HNSCC patients, stratified by ECOG PS. Methods: This retrospective study of the nationwide de-identified electronic health record (EHR)-derived Flatiron Health Advanced H&N database selected patients initiating pembrolizumab monotherapy or pembrolizumab + platinum + 5FU between 07/01/19 - 12/31/20 with follow-up until 07/31/21. Patients with prior platinum-based therapy ≤6 months, prior primary cancers, or treatment with a clinical study drug were excluded. rwToT was defined as length of time between first and last documented administration date pembrolizumab. Patients with a record of next line of therapy, death, or treatment gap ≥120 days from the last administration date were considered discontinued. Patients without a discontinuation event were censored at the end of follow up. Kaplan-Meier analysis was conducted to assess median rwToT and landmark on-treatment rates. All results were stratified by ECOG PS 0-1 (similar to KEYNOTE-048, the registrational clinical trial) and ECOG PS 2-3. Results: A total of 402 patients initiated 1L treatment with pembrolizumab therapy. Of those patients, 297 (73.9%) had a recorded ECOG PS score, majority with an ECOG PS score of 0/1 (Overall: 77.8%, pembrolizumab monotherapy: 70.5%, pembrolizumab + platinum + 5-FU: 84.1%). The median rwToT was higher among the ECOG 0/1 patients compared to ECOG 2/3 patients for both regimens (pembrolizumab monotherapy: 4.4 vs 2.2 months, pembrolizumab + platinum + 5-FU: 5.0 vs 3.5 months). Conclusions: In the real-world, treatment duration with pembrolizumab monotherapy or pembrolizumab+platinum+5-FU in 1L R/M HNSCC was similar to KEYNOTE-048, when restricted to a trial-matched population of ECOG PS 0-1 patients. Treatment duration tended to be shorter in the real-world ECOG PS 2/3 population, who are commonly excluded from clinical trials.[Table: see text]
PEP503 (NBTXR3), a radioenhancer, in combination with concurrent chemoradiation (CCRT) in locally advanced or recurrent head and neck squamous cell carcinoma (HNSCC): Dose-finding of a phase 1b/2 trial.
Authors: Wang Cheng-Hsu , Chao K.S.Clifford , Chen Ping-Tsung , Yeh Kun-Yun , Chen Yen-Chao , Chen Yao-Liang , Yang Shih-Wei , Wu Tsung-Han , Chang Pei-Hung , Young Chi-Kuang , Tsan Din-Li , Tsai Ming-Hsui , Hsieh Ching-Yun , Chen Wen-Cheng , Tsai Yuan-Hsiung , Hsu Cheng-Ming , Chang John W. C. , Yu Wei-Che , Shen Bor-Nian 
Published: June 2022

e18041 Background: PEP503 (aka NBTXR3), a novel radioenhancer composed of functionalized hafnium oxide nanoparticles, is designed for intratumoral injection to increase radiation energy deposition within solid tumors and subsequent tumor cell killing, without increasing toxicity to surrounding healthy tissue. PEP503 nanoparticles plus RT has been tested in elderly HNSCC patients and has demonstrated a good safety profile. The phase 1b part of the study aimed to test the feasibility and the recommended phase 2 dose (RP2D) of PEP503 intratumoral injection when added with low-dose (LD) weekly cisplatin-containing chemoradiation (CCRT) in HNSCC. Methods: Patients who had T3-4 locally advanced HNSCC suitable for CCRT were eligible. An intratumoral single injection of PEP503 was performed 24 to 72 hours before the start of CCRT: consisting of IMRT (70̃72 Gy, 2-2.12 Gy/fraction) and weekly cisplatin (low dose, 40 mg/m2) concurrently during IMRT. Traditional 3+3 design was planned for dose escalation and 5 levels of PEP503 were planned, including 5%, 10%, 15%, 22%, and 33% of the baseline GTV by MRI. PEP503 Intra-tumor dispersion was anayzed by CT-scan. Results: Twelve (12) patients (male/female: 11/1; oral cavity/oropharynx: 11/1) were enrolled, with 3, 6, and 3 patients at 5%, 10%, and 15% PEP503 dose levels, respectively, in combination with LD cisplatin CCRT. DLTs were observed in one patient at 10% dose level which were G3 ALT and G3 AST increased. Common G3 AEs observed across dose levels were stomatitis (50.0%), WBC decreased (33.3%), decreased appetite (16.7%), neutrophil count decreased (16.7%), and leukopenia (16.7%), and only one G4 AE (hyponatraemia) was observed. CT images demonstrated PEP503 within the tumor contour after injection throughout the CCRT period. Hafnium, for all patients, was either not detected or below the Lower Limit of Quantification (LLOQ) in the circulation 60 minutes after PEP503 intratumoral injection, and not found in urine. DCR was achieved in 100% of patients with responding patients for an ORR of 58.3%. No subjects received salvage surgery after study treatment. Study was terminated early before MTD and RP2D could be determined. Conclusions: Adding PEP503, a radioenhancer, via a single intratumoral injection to weekly cisplatin-containing CCRT was feasible and safe for patients with locally advanced or recurrent LA-HNSCC. RP2D was not reached due to study early termination. Clinical trial information: NCT02901483.
High-risk non-16 human papillomavirus genotypes in head and neck squamous cell carcinoma.
Authors: Wotman Michael , Ferrandino Rocco , Gold Brandon , Albstein Nicole , Alpert Naomi , Junn Jacqueline , Westra William , Posner Marshall R. 
Published: June 2022

e18052 Background: Oropharyngeal cancer patients with Human Papillomavirus (HPV)-associated disease have more favorable outcomes. HPV16 is the primary genotype in this population. Our knowledge of the impact of high-risk non-16 HPV (HRN16) subtypes on survival is limited. The objective of this study is to investigate the incidence, demographics, and survival outcomes of HRN16 genotypes in patients with HPV-positive head and neck squamous cell carcinoma (HNSCC). Methods: This is a retrospective chart review of patients diagnosed with HPV+ HNSCC from 2012-2021 at the Mount Sinai Health System. Genotyping was performed with polymerase chain reaction (PCR). Demographic, clinical and tumor data was extracted from electronic medical records.The primary outcomes are overall survival (OS) and event-free survival (EFS) for patients with non-metastatic disease at presentation, treated with curative-intent, with > 6 months follow-up.Survival analysis was performed by Kaplan-Meier method. Results: 733 patients had HPV+ HNSCC, and 109 (14.9%) are HRN16 subtypes. Mean age at diagnosis is 62.4 years. Most individuals are non-Hispanic white males, non-active smokers, social drinkers, and have good performance status (Table). A majority has non-metastatic oropharyngeal cancer treated with standard of care (SOC) definitive therapy. The predominate genotypes are HPV35 (39.4%, n = 41), HPV33 (27.9%, n = 29), and HPV18 (14.4%, n = 15). Survival analysis demonstrated no significant differences in OS (log-rank p = 0.90) and EFS (log-rank p = 0.19) among the different HRN16 subtypes. There was a trend for better EFS for HPV35. Conclusions: HRN16 genotype may not meaningfully impact patient outcomes in HNSCC. Larger multivariate analyses may identify specific site and genotype differences in survival comparedwith HPV16-assoicated disease and indicate if patients with selected HRN16 subtypes are candidates for treatment de-escalation.[Table: see text]
Can immediate reconstruction with submandibular gland transposition broaden indications for transoral surgery for tonsillar cancer?
Authors: Robert Wang , Bigcas Jo-Lawrence , Okuyemi Oluwafunmilola , Yang Albert , Young Allen 
Published: June 2022

e18054 Background: Stratification based on pathologic parameters allows for reduced adjuvant radiotherapy in intermediate risk and observation alone for low risk oropharyngeal p16+ cancer (E3311 ECOG-ACRIN trial). Selection for transoral surgery (TOS), usually robotically assisted, for tonsillar cancers depends on the size and invasiveness of the primary tumor, involvement of adjacent parts such as the soft palate, proximity to external carotid artery branches, medial ipsilateral carotid artery that might be exposed with radical resection, and the likelihood of substantial communication between the oropharynx and internal neck structures. Postoperative recovery can be associated with substantial pain and dysphagia and a length of stay of > 5 days. There is a paucity of simple options for sealing the neck from the pharynx to prevent neck infection, exposure of larger vessels and salivary fistula, so large and deep tonsillar cancers are usually given chemoradiation. Larger surgical defects healing secondarily tend to require longer recoveries due to dysphagia and odynophagia. Methods: A prospective study of vascularized ipsilateral submandibular gland transposition flaps to primarily repair the surgical defect after TOS to resect previously untreated tonsillar cancers was performed from 2019 to 2022. A total of 19 patients underwent resection and repair. These included those with cancers extending to the soft palate (4) and medial position of internal carotid artery adjacent to the tumor (1). All had obvious communication between the neck and the pharynx after TOS, and had branches of the facial and external carotid arteries to the deep resection site ligated with neck dissection, prior to TOS. The submandibular gland flaps were sewn in place using robot assistance and hand. One patient had an extended flap with accompanying submental skin to repair the soft palate. Results: Partial dehiscence superiorly at the palate was the most common complication at 11%. None developed salivary fistulas or deep neck infections. Iatrogenic facial artery pedicle injury that was repaired occurred in one case. Oral intake was started at 1-3 days and length of stay averaged 5 days. There were no bleeding episodes at the TOS sites of cancer resection. All resections had clear margins. All submandibular gland flaps survived, with one patient having attached adipose tissue debrided in the office, healing uneventfully thereafter. Conclusions: The ability to primarily repair after resection of more extensive tonsillar cancers, that leave large communications between the pharynx and the neck, with a readily accessible and easy to harvest submandibular gland flap may change those previously selected for chemoradiation to be able to have TOS instead as initial treatment. This would allow for more pathological risk assessment of tonsil cancers and decreased adjuvant treatment when appropriate.
Osteoradionecrosis in head and neck cancer patients: Risk factors and comparison of grading systems.
Authors: Lee Junhyung , El-Maghrabi Amr , Keshavarzi Sareh , Xu Wei , Huang Shao Hui , Waldron John , Kim John , Ringash Jolie , Hahn Ezra , Cho John , Bratman Scott Victor , Eng Lawson , de Almeida John R , Goldstein David Paul , Irish Jonathan Crawford , Chepeha Douglas Brian , Hope Andrew J. , Glogauer Michael , Watson Erin , Hosni Ali 
Published: June 2022

e18057 Background: We aimed to identify the incidence and risk factors for osteoradionecrosis (ORN) in head and neck cancer (HNC) patients. We also compared frequency of severity scores across different ORN grading systems. Methods: Retrospective review was conducted for HNC patients who were managed at our institution (2011-2018) with curative-intent definitive, pre- or post-operative intensity-modulated radiation therapy (IMRT) with 45Gy, and underwent pre-IMRT dental evaluation. Jaw ORN was defined based on: 1) clinical signs (exposed bone, bone spicules, sequestra, infection and fistula), 2) radiological finding (abnormal bone pattern, radiographic sequestra and pathological fracture), and 3) treatment required and response to therapy, either conservative (chlorhexidine rinse, antibiotics, PENTOCLO, and hyperbaric oxygen) or surgical (sequestrectomy, debridement, and jaw resection). ORN events were retrospectively graded using 6 different grading systems. Pre-IMRT periodontal condition (PC) was classified by universal multi-dimensional staging system based on number of teeth and bone loss (stages 0 to IV). Multivariable analysis (MVA) using logistic regression was applied to identify risk factors of ORN. Results: A total of 2735 HNC patients were included; median age 61 years, 30% (n = 807) current/ex-smokers, 72% (n = 1914) had moderate to severe PC (stage II-IV), 53% (n = 1459) oral cavity/oropharynx (OC/OP) primary tumor. The median IMRT dose was 70Gy/35 fractions, 43% (n = 1170) received concurrent chemotherapy, and 37% (n = 1006) underwent surgery. A total of 227 patients (8.3%) developed ORN. There was discrepancy in different grading system for capturing and reporting the degree of severity (i.e. grade) of ORN (table). On MVA, risk factors for ORN were: current/ex-smoker (OR 1.5, 95% CI: 1.12-2, p< 0.01), stage II-IV PC (OR 1.7, 95% CI: 1.17-2.36, p< 0.01), primary OC/OP tumor (OR 4.4, 95% CI: 3.08-6.29, p< 0.001], and IMRT dose prescription ≥60Gy (OR 3.5, 95%CI: 1.11-11.33, p< 0.01). Conclusions: ORN is relatively uncommon in HNC patients, however it can be under-reported by different grading systems. Risk factors for ORN were: smoking history, pre-IMRT poor PC condition, OC/OP primary tumor, and higher dose (≥60Gy) IMRT.[Table: see text]
Changing patterns of second primary malignancies and cause-specific mortality among patients with major salivary glands cancers in the United States: A population-based study.
Authors: Chamarti Karthik , Bakhati Bibek , Rudraraju Vasudha , Mannem Maneesh , Rajput Maryam , Garza John , Bajaj Kelash 
Published: June 2022

e18081 Background: Salivary gland neoplasms are rare entities that comprise approximately 5% of all head and neck malignancies. The incidence of major salivary gland (MSG) cancers has increased about 54% from 1970 to 2000 in the United States (US). We undertook this study to investigate the risk of second primary malignancies (SPMs) and cause-specific mortality (CSM) in patients with MSG cancers using a national registry from the US. Methods: We estimated the incidence of SPMs among two-month survivors of MSG cancers using the Surveillance, Epidemiology, and End Results (SEER)-18 registries between 2008 to 2018. The risk of SPMs were calculated using standardized incidence ratios (SIRs) and the CSM by standardized mortality ratios (SMRs) and absolute excess risk (AER)/10,000 population. Results: We included 845 patients with MSG cancers in this study. The median age of diagnosis was 67 yrs (range 0 - 85 yrs). The median follow-up duration was 24 months (range 0 - 130 months). The median latency period for SPM development was 30 months (range 4 - 117 months). A total of 38 (4.5%) patients developed 41 SPMs at last follow-up. The SPM risk for cohort was significantly elevated (SIR = 1.81, 95% confidence interval [CI] = 1.30 - 2.46) compared with general population. The SPM risk was statistically higher among males (SIR = 2.42, 95% CI = 1.66 - 3.42) but not significant in females (SIR = 0.95, 95% CI = 0.44 - 1.81). Specific sites with highest SPMs risk included tonsil (SIR = 52.45, 95% CI = 1.33 - 292.22) followed by oral cavity (SIR = 15.55, 95% CI = 7.11 - 29.52). The risk for tonsil cancers were high from 5 to 10 years of initial diagnosis. While risk for oral cavity cancers, remained high throughout follow-up period. At the last follow-up, 214 (25%) patients had died. There was statistically significant risk of mortality due to MSG cancers (SMR = 5,453.61, 95% CI = 4,385.34 - 6,703.41, AER = 517.87) and oral cavity cancers (SMR = 663.40, 95% CI = 537.97 - 809.29, AER = 557.41) (Table). Conclusions: Our study concludes that men with MSG cancers are at an increased risk for SPMs compared to women. The risk of specific SPMs (tonsil and oral cavity cancers) was high even after a long period from the initial diagnosis of MSG cancers. This highlights the need for long-term surveillance in these patients for SPMs development.[Table: see text]
Trends in early phase clinical trials: A tale of exponential economic growth and access.
Authors: Reddy Neha K. , Coleman Niamh , Subbiah Vivek 
Published: June 2022

e18504 Background: There has been exponential economic growth in the BRIC (Brazil, Russia, India and China) nations in recent years, and outsourcing of clinical trials to these countries has occurred in tandem. Our study aimed to assess the current status of early phase oncology clinical trial recruitment in the BRIC countries, to assess the impact of these emerging economies and global markets in health care. Methods: We reviewed the open-access clinical trial registry, clinicaltrials.gov, for registered interventional recruiting early phase trials (Phase I/II) in the BRIC countries in adults and analyzed each country separately and collectively. We extracted descriptive data and established a database and proceeded to perform literature review and examine trends in early phase clinical trials. Results: We identified 888 recruiting early phase clinical trials in BRIC countries; China had 95% (842/888) of the trials, Brazil 1.5% (13/888), Russia 3.4% (30/888) and India 0.34% (3/888). For tumor specific studies, gastrointestinal (17%, 148/888), lung 11% (94/888) and breast (17%, 53/888) cancers were the most studied. Most trials were industry-sponsored (76%, 675/888); and most conducted in a single country (95%, 846). Industry-sponsored studies comprised 96% in China (635/842), 87% in Russia (26/30), 92% in Brazil (12/13), 67% (2/3) in India. Overall, immunotherapy agents in single and combination treatment strategies were the most common agent under investigation, with novel therapies such as CAR T-cell therapy (eg. CAR-T/TCR NK-CAR CAR-T/TCR-T Cell) being increasingly used in China (168 single agent trials, 30 trials in combination: 24% of trials in China). In contrast, CAR T-cell therapy trials were not yet in BRIC nations outside of China. Combination studies were frequent (33%, 293/888), and included a variety of combination strategies utilizing targeted therapies, immunotherapies, chemotherapies, antibody drug conjugates and novel biologics. Conclusions: Despite the economic explosion and shift of non-oncology clinical trials to BRIC nations, US and Europe continue to dominate in the design and conduct of early phase clinical trials in hematology and oncology. However, there has been exponential growth in early phase trial testing in China, which now accounts for 18.5% of the world’s population and has the majority (95%) of trials in BRIC nations. Contrastingly, India, which accounts for 17.7% of world’s population, has < 1% of BRIC nation trials. In keeping with trends in the US and Europe, there is a dominance of industry-sponsored studies in BRIC countries. Globally, early phase trials are increasing in their complexity with ongoing interest in immune modulation as a treatment strategy.