bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronotherapy in head and neck cancer (HNC): A systematic review.
Authors: Abu-Samak Abdel-Azez , Abu-Samak Mohammad , Al-Waeli Haider , Cai Wenji , Al-Tamimi Mohammad , Tamimi Faleh , Nicolau Belinda 
Published: June 2023

e18016 Background: Chronotherapy in cancer is optimizing the administration time of anti-cancer treatment according to circadian rhythm and cellular phase to improve the efficacy against tumor cells while decreasing side effects on normal cells. Several randomized controlled trials (RCT) evaluated chronotherapy of chemotherapy (chrono-chemotherapy: time-specific infusions) and/or radiotherapy (chrono-radiotherapy: morning radiotherapy) in various cancers and reported improved treatment efficacy and reduced toxicity. However, the effect of chronotherapy in HNC treatment is unclear as there are no prior systematic reviews reported. Therefore, this systematic review summarizes available clinical evidence on the effect of chrono-chemotherapy (CCT) and chrono-radiotherapy (CRT) on treatment response and adverse events in HNC adult patients. Methods: We conducted a systematic search using Medical Subject Headings (MeSH) in four online databases (OVID, Embase, CINAHL and Scopus), and 6078 articles identified were published in English between the databases' inception date and June 30, 2022. We included original peer-reviewed retrospective and prospective human studies investigating CCT and/or CRT versus conventional treatments in HNC patients. We excluded articles that contained no abstract, were unrelated to HNC, were pre-clinical and case reports, or did not include time-specific interventions in their methods. Results: 16 studies were finally included. Overall, studies were heterogenous in demographics, study design, intervention, and outcome measures, thus meta-analysis could not be performed. Nine studies (RCT = 3, Non-RCT = 2 & Retro = 4) investigated CRT. Squamous cell carcinoma (SCC) was mainly reported as the primary tumor (stage I-II). 7/9 studies reported a significant reduction in the incidence of oral mucositis (Grade ≥3) in the CRT group as opposed to conventional radiotherapy (RT) groups (p < 0.05). In contrast, treatment response was investigated in 4/9 studies and was insignificant (p > 0.05). Seven studies (RCT = 5 & Retro = 2) investigated CCT in patients diagnosed with SSC (stage II-IV). All included studies had concurrent RT. Different chemotherapeutic agents were used in combinations or as a single agent, namely Cisplatin, 5- Fu, Paclitaxel and Docetaxel. CCT groups in all studies achieved a significant reduction in Nausea & Vomiting (Grade ≥3), while a significant reduction in Leukopenia & Thrombocytopenia (Grade ≥3) was reported in 2 studies only (p < 0.05). Treatment response (OS and PFS) was not significantly different (p > 0.05) between both groups except 2 studies reported significantly higher ORR in chronotherapy groups (p < 0.05). Conclusions: CCT and CRT in HNC treatment in most studies provided evidence of toxicity reduction while treatment response was maintained. However, large multicentric randomized controlled studies with standardized protocols and optimized designs are still needed.
A retrospective study evaluating the efficacy of pembrolizumab for metastatic or locally recurrent head and neck cancer: A real-world experience.
Authors: Pirruccello Jonathan P. , Afzal Muhammad Zubair , Palmer John P , Dore Maura , Shirai Keisuke 
Published: June 2023

e18018 Background: Metastatic and locally recurrent head and neck cancer is an unfortunate occurrence and is associated with a historically poor prognosis. The KEYNOTE 048 trial reported an overall response rate (ORR) of 17% in this patient population after treatment with pembrolizumab. The purpose of our study is to evaluate the real-world outcomes in patients with metastatic or recurrent head and neck cancers treated with pembrolizumab or pembrolizumab containing regimens at our NCI designated comprehensive cancer center. Methods: We reviewed the medical records of 39 patients with advanced head and neck cancers treated with pembrolizumab or pembrolizumab containing regimens between 9/1/2017 and 12/31/2021. Patients with a diagnosis of cutaneous squamous cell carcinoma in the head and neck region and nasopharyngeal cancers were excluded. Results: Thirty-seven patients were included in the final analysis with a median age of 67. The median time to last follow-up was 12 months with a median time on therapy of 3.2 months. The most common location was oropharynx (87%), and 59% of the study population had documented CPS scores greater than 1. Approximately 60% of patients had distant metastatic disease at the time of initiation of pembrolizumab including one patient with symptomatic brain metastases prior to initiation of therapy. The most common site of metastatic disease was the lungs (51%). The ORR was 11.7%, while the median OS and median PFS were 10 and 2.9 months, respectively. Three patients experienced a complete response (CR), including one patient with a lasting, durable response of 50.9 months. The six-month and one-year PFS were 100% in those who responded or had stable disease (five patients). Ten patients (27%) required hospitalization due to treatment related adverse effects. Conclusions: The role of pembrolizumab in the setting of advanced head and neck cancer is well-established based on findings from large clinical trials. We report an ORR of 11.7% and median PFS of 2.9 months in patients treated with pembrolizumab containing regimens. Although the findings of our small retrospective study suggest a lower response rate than previously reported, the progression free survival in responders at six and twelve months was 100%. Identification of potential responders to immunotherapy has been an active area of research and our study suggests that a subset of patients with metastatic and/or locally recurrent head and neck cancer may experience long and durable responses to pembrolizumab containing regimens. [Table: see text]
Long term disease-free survival in locoregional, metastatic and/or recurrent UCNT.
Authors: Hadji Imène 
Published: June 2023

e18023 Background: Undifferentiated Carcinoma of Nasopharyngeal Type (UCNT) is a rare and aggressive type of head and neck cancer related to the Epstein Barr virus (EBV), genetic (HLA B5 in Algeria) and environmental factors. It is the most frequent histological variant of ENT cancers. It has geographically selective epidemiologic features unrelated to external carcinogens, and is known to be radiosensitive and chemosensitive. Methods: Seventy-one patients with biopsy-proven UCNT presenting to a single oncology unit between 2015 and 2022 were assessed for their long-term response to treatment. The sex ratio of cases was 3M: 1F; thirty-one patients (43%) were under the age of 50; 11 (15%) under the age of 35; and among these, there were two 19 year old males. The initial median World Health Organization (WHO) performance status was 1.6. These patients with locoregional (LR), recurrent (REC) and/or metastatic (MTS) UCNT were treated with monthly cycles of platinum-based chemotherapy of cisplatin (CDDP) 75 mg/m2 IV or Carboplatine AUC-4 and Docetaxel 75 mg/m2 IV followed by fluorouracil (5FU) 1000 mg/m2/day continuous IV infusion days 1 to 4 (TPF) in locally advanced disease, and with cisplatin (CDDP) 75 mg/m2 day 1 or Carboplatine AUC-5; and fluorouracil (5FU) 1000 mg/m2/d continuous IV infusion days 1 to 4 (PF) in recurrent and/or metastatic cases. The choice of systemic therapy was individualized based on patient characteristics including performance status, goals of therapy. Results: Those LR or MTS patients who were still alive without evidence of disease after 36+ months were categorized as complete responders (CRs). A subgroup of CRs was identified who had failed prior chemotherapy. MTS patients with less than three distant osseous sites underwent additional radiation therapy. Conclusions: Encouraging results for this particular type of head and neck cancer confirm the chemosensitivity of UCNT, and the observation of long-term responders makes curability a real consideration.
Metastases harbored in the maxillofacial region: Patient and cancer related characteristics and outcomes.
Authors: Turgeman Shahar , Turgeman Ilit , Emodi Omri , Wolff Amir , Rachmiel Adi 
Published: June 2023

e18029 Background: Maxillofacial metastases from distal primary sites are rare, accounting for less than 1% of all newly diagnosed cancer in the head and neck region. Clinical manifestation is non-specific and lesions are often misdiagnosed as benign or inflammatory lesions, and mistreated. We sought to describe maxillofacial metastases and evaluate associations with treatment and patient related outcomes. Methods: Data from all patients diagnosed with cancer in the maxillofacial region between 2008-2020 were extracted retrospectively from the hospital registry, and those with radiological and histological evidence of metastatic lesions were included in the analysis. Patient demographics, clinical presentation, features of primary cancer and treatment were collected. Paired t-tests and univariate regression models were used to evaluate an association between variables and overall survival (OS). Results: Of 532 patients diagnosed with cancer in the maxillofacial region, 15 (2.8%) were found to have metastases from distal primary cancers and included in the study. The group comprised 8 males (53.3%) and 7 females (46.6%), mean age 69 years (range 43 -88) and most common primary malignancies were lung (27%), gastrointestinal (27%) and prostate (20%), with 60% adenocarcinoma histology and the rest SCC and undifferentiated carcinoma. Presenting symptoms included trismus, pain, and swelling in 40% of cases. Clinically, most intraoral manifestations were classic oral ulcerations while the most frequent extra oral features were diffuse pre-auricular and mandibular swelling. Mean time to diagnosis was 22 days (range 7-60), however, intraoral lesions were diagnosed numerically earlier than extra oral (18 vs 23 days, p = 0.5). The mandible was the primarily involved hard tissue location (40%), and the parotid, for soft tissue lesions (33%). Mean SUV for PET-CT scans was 4.4 (range 2.0-10.93) and CT demonstrated bone expansion and lysis (50% each) and periosteal reaction (33%). In total, 60% of patients in the study had a change to their treatment after diagnosing the metastasis, while 40% with direct radiation (30-70 Gy) to the metastatic site. Median OS was 5 months while 60% of patients in the study group survived less than 6 months. Despite being twice as likely to receive treatment (75% vs 37.5%), patients with intra oral metastases had significantly shorter survival than those with extra oral metastases (13.3 vs 2.9 months, 95% CI 3.025-17.689, p < 0.01). No other associations were observed between patient demographics, cancer type and treatment, with survival. Conclusions: The maxillofacial region appears to be a late site for cancer metastasis, with non-specific presentation. As patient survival outcomes improve across cancer types and the array of possible alternative diagnoses increases, clinicians should be aware of this entity to ensure rapid referral for diagnosis and palliative treatment.
Combinatorial immune biomarkers of efficacy on buparlisib and paclitaxel in patients with SCCHN: BERIL-1 sub-analysis.
Authors: Soulieres Denis , Lucas Justin , Xu Sherry , Lu Sunny , Dreyer Kevin , He Nanhai , Tang Tom , Birgerson Lars E , Licitra Lisa F. , Faivre Sandrine 
Published: June 2023

e18030 Background: Previous analysis of the BERIL-1 Phase 2 clinical trial (Soulieres et al, CCR, 2018), evaluating the efficacy of Buparlisib + Paclitaxel, was one of the largest genomic landscape analyses to date in metastatic SCCHN. With the recent approval of PD-1 in this indication, we sought to expand the analysis, focusing on combinatorial biomarkers of immune infiltration in addition to specific genomic alterations. The goal is to evaluate hierarchically prognostic and predictive biomarkers to select predefined analysis in the current Phase 3 clinical trial, BURAN (NCT04338399) post immune modulatory therapy. Methods: The results of this analysis focused on combination of genomic alterations in both tumor and plasma samples. Alterations found in tumor versus plasma revealed over 50 differentially altered genes. Combination of these sample types is more comprehensive of the patients’ true mutational and copy number status; no significant differences in alteration frequency between treatment and placebo treatment arms were identified. We evaluated correlations between select biomarkers and improvement in efficacy end points of Progression Free Survival (PFS) and Overall Survival (OS) between the treatment and control arms and within the treatment arm. Results: The most frequently altered genes were, TP53 (49%), NOTCH1 (21%), PIK3CA (19%), FAT1 (15%), and CDKN2A (13%). Previous analysis demonstrated that TP53 mutations as well as high immune infiltration (> 10% intratumoral or stromal TILs) showed improvement in PFS & OS. Further improvement to OS was observed in subjects with high immune infiltration and TP53 (p = .031, HR = 0.52), PIK3CA (p = .005, HR = 0.34), NOTCH1(p = .046, HR = 0.13) or FAT1(p = .007; HR = 0.28) alterations when compared to non-altered subjects in the treatment arm. Further improvement to PFS was observed in subjects with high immune infiltration and TP53(p = .031, HR = 0.52) or FAT1(p = .006, HR = 0.23) alterations when compared to non-altered subjects in the treatment arm; NOTCH1 alterations showed strong trends in improved PFS. Additionally, high tumor mutational burden (TMB) combined with alterations in the TP53 pathway showed significant OS improvement (p = .052, HR = 0.44) compared with the placebo arm. Conclusions: This analysis highlights unique insights into the mechanism of Buparlisib and Paclitaxel in of metastatic SCCHN patients; a significant improvement in efficacy observed when specific alterations are considered in the context of immune infiltration. These observations will be further explored in the ongoing Phase 3 clinical trial, BURAN. Additional analysis to be presented at the meeting include prognostic and predictive value of each biomarker and combination, differences between tumor and plasma samples, and comparison with end of treatment samples.
Lactate metabolism as a dictator of patient outcomes and immune microenvironment in head and neck squamous carcinoma.
Authors: Chen Xiaochuan , Pan Junping , Ding Qin , Huang Zongwei , Yang Hanxuan , Qiu Sufang 
Published: June 2023

e18038 Background: Head and neck squamous cell carcinoma (HNSCC) treatment is facing clinical challenges. Recent research reports have highlighted the integral function performed by the tumor microenvironment (TME) in the prediction of clinical outcomes. Lactate metabolism mediates many cancers’ initiation and progression, including metastasis, angiogenesis and immunosuppression. However, the prognostic significance of lactate metabolism-related genes (LMRGs) and the role of TME in HNSCC requires further elucidation. Methods: We built a prognostic multigene signature with LMRGs and systematically correlated the risk signature with immunological characteristics and immunotherapy efficacy. Next, a series of single-cell sequencing analyses were used to characterize lactate metabolism in TME.The most important prognostic gene among risk signature was screened by machine learning analysis. Finally, single-cell sequencing analysis, immunofluorescence analyses, and a series of in vitro experiments were used to explore the role of PYGL in HNSCC. Results: LMRGs-related prognostic model showed good prediction performance. The immunological signaling pathways are linked to low-risk scores. Patients in low-risk group were characterized by low levels of lactate metabolism, high levels of CD8+ T cells infiltration, “hot”immune phenotype and benefit from immunotherapy. Compared with other cells, tumor cells in TME exhibited the most active lactate metabolism. Machine learning analysis highlighted that PYGL was the most important prognostic gene among risk signatures. And lactate concentrations decreased in PYGL knockdown cells. We found that PYGL was highly expressed in macrophages, may inhibit the polarization of M1 macrophages. The inflammatory phenotype was characterized by the least expression of PYGL, which was observed to be inversely linked to CD8+ T-cell infiltration, as determined by immunofluorescence analyses. Conclusions: Our study identified and validated a promising LMRGs signature associated with inflamed TME, which may accurately anticipate the survival of HNSCC patients. PYGL might be a novel biomarker to predict immune efficacy.
Clinical and pathological correlation of p53expression in oral cancers.
Authors: Bellala Venkata Madhavi , Bellala Ravishankar , Haranadh Sriharsha , Kalagara Akash , P Venkateswar Rao , Sowjanya Kasipeta 
Published: June 2023

e18039 Background: p53 is a tumor suppressor protein, its overexpression is associated with survival and response treatment in squamous cell carcinoma of oral cancers. p53 is detectable on immunohistochemistry in carcinogen associated oral squamous cell carcinoma. The aim of this study is to explore the prevalence of p53 expression and its prognostic importance in oral squamous cell cancers. Methods: This study was conducted at Omega hospital during January to December 2021. One hundred fifty five samples were examined on relationship of p53 expression with clinicopathological correlation with a follow up period of 13 months. All the tissue samples spotted in tissue microarray, were submitted to immunohistochemistry assay for qualitative detection of p53 (Hu). IHC was performed using Ventana R BenchMark Ultra using manual. Results: Overall 58 % were p53 mutant positive and 42% were wild type p53. All 155 patients were staged under AJCC, underwent standard treatment including surgery, chemotherapy and radiotherapy. We observed p53 mutation was more prevalent in high grade tumors with 66.7% and 33.3% of high grade tumors had wild type p53 with p value .047 (Pearson chi-square). Patient with p53 mutant and null had more margin positive disease 76.2% compared to p53 wild type 23.8% with p value 0.17 (Pearson chi-square). Mutant and null V patients presented with advanced T stage compared to wild type 36.7% vs 16.1%, p value .009 (Pearson chi-square), node positive disease 58.1% vs 41.9%. Depth of invasion was observed to be more than 20 mm in p53 null and mutant compared to p53 wild 12.2% vs 3.1% p value .037, extra-nodal extension was more in p53 mutant disease compared to p53 wild type 36.7% vs 10.8% with p value of .000 (1 sided Pearson chi-square). The events like local recurrence and death were 58.1% in mutant vs 41.9% in wild type with p value of 0.67 and local recurrence alone was significant with 10.0% in mutant vs 1.5% in wild type of p53. Conclusions: The p53 mutant and null showed greater distinction in clinical presentation and adverse pathological features. The findings suggest that assessing p53 marker in oral cancers will be able to predict the adverse features. Frozen section should be incorporated into the protocol to potentially achieve negative margins. The local recurrence was significantly more in mutant compared to wild type though the deaths were not statistically significant among the groups could be due to shorter follow up period.
Distribution pattern of metastatic lymph nodes in 870 cases of nasopharyngeal carcinoma: A clue for individualized elective prophylactic neck irradiation.
Authors: Wang Lei , Wu Zheng , He Qian , Li Yiting , Wang Subin , Li Feiping , Wang Hui , Li Wenhui , Han Yaqian 
Published: June 2023

e18049 Background: We aimed to explore a potential individualized elective prophylactic neck irradiation (iEPNI) to optimize the current strategy by investigating the distribution of metastatic lymph nodes (LNs) in nasopharyngeal carcinoma (NPC). Methods: Magnetic resonance imaging (MRI) and clinical data of 870 non-distant metastatic NPC patients admitted to the Hunan Cancer Hospital between January 2019 and December 2019 were reviewed. All patients were staged using the 8th TNM staging system, and the LNs location was assigned based on the 2013 guidelines. According to the distribution patterns of the LNs in NPC, the intra-regional lymphatic drainage levels were categorized into the following three stations: Station 1st of level VIIa and II; Station 2nd of level III and Va; and Station 3rd of level IV, Vb, and Vc. Other levels were defined as extra-regional areas. Results: The incidence of LNs metastasis was 822/870 (94.5%), including 198 cases of unilateral metastasis and 624 cases of bilateral metastasis. Among the 870 patients, the most frequently involved intra-regional lymphatic drainage was level IIb (87.1%), followed by level VIIa (80.0%), IIa (61.8%), Va (30.6%), IV (21.4%), Vb (8.9%), and Vc (1.1%). In the extra-regional areas, the detailed LNs distribution was: level Ia (0.2%), level Ib (7.7%), level VI (0.1%), level VIIb (5.6%), level VIII (5.5%), level IX (0.3%), and level X (0.2%). The rates of LNs metastasis in Station 1st, Station 2nd, and Station 3rd were 820/870 (94.3%), 532/870 (61.1%), and 199/870 (22.9%), respectively. Only 4 patients were considered to be skipping metastasis among the three stations (4/870, 0.5%). Additionally, in 203 patients with unilateral Station 1st LNs metastasis, there were 86 (42.4%) and 37 (18.2%) patients with ipsilateral Station 2nd and Station 3rd metastasis, respectively, and 3 (1.5%) and 1 (0.5%) patients with contralateral Station 2nd and Station 3rd LNs metastasis, respectively. Conclusions: LNs spread from Station 1st to Station 3rd successively with rare skipping metastasis. A potential iEPNI strategy of prophylactical neck irradiation to the ipsilateral latter node-negative station might be feasible, which is detailed as follows: irradiation to Station 1st in patients with no LNs metastasis, irradiation to Station 2nd in patients with only Station 1st metastasis, and irradiation to Station 3rd in patients with Station 2nd metastasis but without Station 3rd metastasis. Further prospective investigations are expected to validate the strategy.