bluuebunny/crossref_metadata_2025 huggingface dataset:
The distribution of HPV subtype in vulvar intraepithelial neoplasia and the association with recurrent VIN and vulva cancer in Taiwan.
Authors: Liao MIN-Jie , Lai Chyong-Huey
Published: June 2023

e17635

Background: Vulvar intraepithelial neoplasia (VIN) is a precursor lesion of vulvar cancer. Human papillomavirus (HPV) is causative for part of VIN lesions. This retrospective study aimed to investigate HPV distribution in patients with vulvar intraepithelial neoplasia (VIN) and the factor associated with the recurrence of high-grade vulvar intraepithelial neoplasia (VIN2+), high-grade vaginal intraepithelial neoplasia (VAIN) , cervical intraepithelial neoplasia(CIN) or progression to vulvar cancer. Methods: We retrospectively analyzed patients who diagnosed as vulvar squamous intraepithelial lesions between 1990 and 2014 in our institution. All the diagnoses and classifications were confirmed by two pathologists in 2015 ISSVD terminology. HPV DNA was extracted from formalin-fixed and paraffin-embedded samples. SPF1/GP6+ polymerase chain reaction (PCR) followed by HPV Blot and E6 type-specific PCR were performed. Results: Ninety-eight VIN patients were included in our analysis. Ninety-three percent were positive for HPV and HPV16 (43.9%), HPV6 (11.38%), HPV11 (8.94%), and HPV58 (4.88%) were the most prevalent types. Patients with positive HPV were diagnosed younger than those with negative results (43.0 years vs. 61.1 years, P = 0.049). In 15 patients who with recurrent VIN (n = 11) or progression to vulvar cancer (n = 4), had positive HPV. All 4 patients who had progression to cancer were positive for HPV16 in their initial VINs. High risk type HPV infection, positive HPV16, and positive alpha-9 types are significant risk factors for recurrent VIN and progression to cancer. Conclusions: Positive HPV was detected in 92.8% of VINs and was related to younger age at diagnosis. HPV16 was the most prevalent type and was significantly related to recurrence/ progression. Other significant risk factors for recurrent VIN or progression to cancer were high-risk HPV and alpha-9 types. Closely monitor of those patients with risk factors was indicated for early detection and treatment of recurrent VIN and vulvar cancer.
Social determinants of survival in head and neck cancer.
Authors: Kennedy Kim Robyn , Gibson Daren Joseph , Flukes Stephanie , Spalding Lisa Jane , Diwakarla Chandra Sai , Redfern Andrew David
Published: June 2023

e18008

Background: Social demographics and health inequalities are associated with adverse outcomes in cancer. Methods: We conducted a retrospective review of 320 Head and Neck Cancer patients between 2013-2021 in a tertiary centre in Western Australia. We matched 80 Aboriginal patients with 240 non-Aboriginal patients by disease site, histology, age, and rurality. Data collected included tumour site, patient demographics, treatments, recurrences, and survival outcomes. An initial univariate analysis was performed using Chi-Square and Kaplan Meier analyses; however a multivariate analysis will be conducted for subsequent publication. Results: Median follow-up was 2.6 years (range 16 days to 9 years). 44% of patients underwent curative intent radiotherapy or chemoradiotherapy, 38% had surgery (+/- adjuvant therapies), 9% had palliative treatments, and 9% had best supportive care. Overall survival (OS) using Kaplan-Meier was inferior for Aboriginal patients compared with non-Aboriginal patients; 1 year survival (YS) 59% vs 85% and 5YS 32% vs 60% (p < 0.00001). Of patients receiving curative intent treatment, relapse occurred in 47% of Aboriginal patients compared with 29% of non-Aboriginal patients (p = 0.01), with inferior progression-free survival (PFS) 1 yr PFS 71% vs 81% and 5yr PFS 52% vs 72%, p = 0.006. 2YS was highest in regional patients (77%), followed by metropolitan (68%), and lowest in remote patients (61%), p = 0.04. 21% of remote patients opted for palliative treatment despite curative treatment being recommended, compared with 3% of regional and 4% of metropolitan patients. Amongst patients receiving curative treatment (81%), metropolitan patients had the highest risk of relapse (42%), compared with remote (31%) and regional (23%), p = 0.02. Despite this, in the same group of treated patients, remote patients had the lowest survival (2YS 88% regional, 80% metropolitan, 75% remote, p = 0.04). Ever smokers had lower 1YS (91% vs 76%, p = 0.03), a higher risk of relapse (28% vs 21%, p = 0.01), and a lower likelihood of disease-free survival (53% vs 74%, p = 0.01) compared to never smokers. Alcohol excess was associated with inferior 1YS (84% 0-4 std/d, 85% 5-10 std/d, 57% > 10 std/d, p = 0.00004), and a higher risk of relapse (19% for non-drinkers, 35% 1-4 std/d, 27% 5-10 std/d, and 64% for > 10 std/d, p = 0.00007). Marital stability was associated with improved 1YS (88% married, 78% widowed, 78% de facto, 76% divorced, 65% single, p = 0.004). Single patients had the lowest likelihood of disease-free survival (42%), followed by divorced (50%), de facto (50%), and widowed (65%). Married patients had the best disease-free survival (66%), p = 0.002. Non-English speaking status was associated with inferior 1YS (79% vs 40%, p = 0.006). Conclusions: Aboriginal status, rurality, smoking, high alcohol consumption, single or divorced individuals, and non-English speaking were all associated with poorer outcomes.
Chemotherapy combined with anlotinib, toripalimab and stereotactic radiotherapy in oligo-metastatic nasopharyngeal carcinoma: A prospective, multicenter phase II clinical study.
Authors: Yang Dong , Hu Xueying , Ruan Lin , Yang Zhendong , Zhang Tingting , Qin Yutao , Liu Kang , Liang Fangfang , Qin Yating , Huang Heqing , Li Pian , Du Guobo , Lu Ying , Han Yaqian , Wang Rensheng , Kang Min
Published: June 2023

e18011

Background: Distant metastasis is the main cause of nasopharyngeal carcinoma (NPC) related death while there are few treatment options for it. How to further improve the survival of NPC patients with distant metastases is an urgent problem to be solved in clinical practice. This study investigated the efficacy and safety of chemotherapy in combination with anlotinib (a multi-target tyrosine kinase inhibitor), toripalimab, and stereotactic radiotherapy(SBRT) in treatment of metastatic NPC. Methods: This is a prospective, multi-centered, single-arm, phase II trial (ChiECRCT20210147). Patients with histologically confirmed non-keratinous carcinoma and post-treatment metastatic NPC (stage IVb, AJCC 8th) who had no local recurrence and received no systemic antitumor therapy for metastatic lesions previously were enrolled. No more than 5 metastatic lesions (metastatic sites include lung, liver, bone, etc.), and with at least one measurable target lesion according to RECIST1.1. Other inclusion criteria included 18-65 years old and ECOG 0-1. All patients received gemcitabine (1000 mg/m2, ivgtt, d1/8), cisplatin (80 mg/m2, ivgtt, d1), toripalimab (240mg, ivgtt, d1) and anlotinib (12mg, oral, qd, d1-14) every 3 weeks for 6 cycles, then followed by toripalimab (240mg, ivgtt, d1) and anlotinib (12mg, oral, qd, d1-14) every 3 weeks for 11 cycles. The SBRT was initiated after 2 cycles of chemotherapy (bone GTV 30-45Gy/3-5f, liver and lung GTV 45-60Gy/4-6f). The primary endpoint was objective response rate (ORR). Here we report the results of a preliminary analysis. Results: Between January 2022 and January 2023, a total of 19 patients were enrolled (13 males and 6 females), the median age was 46 years old. At the data cutoff date on January 31, 2023, 15 patients were eligible for the evaluation of tumor response with metastatic lesions. 100% of the patients (15 of 15) had a response and the confirmed ORR was 100% (complete response, n = 4; partial response, n = 11) for metastatic lesions. The most common treatment-related adverse events (TRAE) of any grade were leukopenia (15 of 15,100%), anaemia(13 of 15, 93.3%), decreased appetite (10 of 15, 66.7%), hypothyroidism (6 of 15, 40.0%), rash(5 of 15, 33.3%) and pneumonitis (5 of 15, 33.3%). Grade 3-4 TRAE included leukopenia (3 of 15, 20.0%) and no fatal adverse events occurred. Conclusions: This preliminary analysis indicated that chemotherapy combined with anlotinib, toripalimab, and stereotactic radiotherapy had promising efficacy and favorable tolerance as treatment of oligo-metastatic NPC. Clinical trial information: ChiECRCT20210147 .
Comparison of first-line treatments for recurrent or metastatic nasopharyngeal carcinoma based on phase 3 randomized clinical trials.
Authors: Xiong Wei , Zhu Lixiu , Xu Guoqiang , Xia Yaoxiong , Wang Hu , Xu Tianrui , Li Xin , Xue Yongyuan , Li Zhengfei
Published: June 2023

e18012

Background: Guidelines recommend platinum-based chemotherapy as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) patients. There are a variety of available combination treatment options, however, there is lack of research evaluating their advantages and disadvantages. Therefore, this study aims to compare the efficacy and adverse events (AEs) of the first-line treatment for R/M NPC. Methods: PubMed, EMBASE, Web of Science, and the Cochrane Library were systematically searched for phase 3 randomized clinical trials (RCTs) in which two first-line treatments for R/M NPC were compared. Among the included trials, progression-free survival (PFS) and overall survival (OS) were calculated using the hazard ratio (HR) and 95% Bayesian confidence interval (95% CrI), while the odds ratio (OR) and 95% CrI were used to evaluate the incidence of severe AEs. The cumulative ranking plot and surface under the cumulative ranking curve (SUCRA) were used to evaluate the rank probability of each regimen. Results: Three trials involving 4 total regimens were included. In terms of PFS, toripalimab plus gemcitabine plus cisplatin (GP) (HR: 0.28; 95% CrI: 0.081-0.98) and camrelizumab plus GP (HR: 0.28; 95% CrI: 0.079-0.96) were significantly superior to fluorouracil plus platinum (PF). In the rank analysis, camrelizumab plus GP was most likely to be the best regimen (SUCRA = 0.81), followed by toripalimab plus GP (SUCRA = 0.80). There was no significant difference among these treatments in terms of OS or AEs. Conclusions: This is the first network meta-analysis comparing the pros and cons of first-line regimens for R/M NPC based on phase 3 randomized clinical trials. Our research showed that toripalimab/camrelizumab plus GP was found to be the most effective treatment regimens for the first-line treatment for R/M NPC in terms of PFS.
Evaluating the efficacy and safety of pembrolizumab monotherapy or in combination with standard chemotherapy in the first-line treatment of locally recurrent head and neck squamous cell carcinoma in different TP53 and PI3K statuses.
Authors: Zhang Shurong , Zhang Boyao , Li Xinyu , Dang Shoutao , Zhao Jingyang
Published: June 2023

e18014

Background: Pembrolizumab (pembro)-based therapy is currently widely used in recurrent/metastatic head and neck squamous-cell carcinoma (R/M HNSCC). The study will explore the association between different TP53 and PI3K statuses and survival in locally recurrent HNSCC. Methods: This is a prospective, single-center study analyzing patients with locally recurrent HNSCC and prior platinum-based chemotherapy for at least 6 months without progression. Patients received pembro monotherapy (200mg) or pembro plus standard chemotherapy (PF, TP, P, G, GP; paclitaxel 175mg/m2, cisplatin 100 mg/m2, 5-fluorouracil 1000 mg/m2 per day for 4 consecutive days, Gemcitabine 1000mg/m2 day 1 and day 8) every 21-day for 6 cycles and followed by pembro maintenance therapy until progression or unacceptable toxicity or 35 cycles, whichever occurred first. Patient’s response to the therapy was evaluated using RECIST 1.1. Primary endpoint was PFSITT,PFSTP53mut,PFSTP53wt, PFSPI3Kmut/amp and PFSPI3Kwt. Secondary endpoint was ORR, DCR and OS of ITT patients and combination group. Results: From January 8, 2020 until September 20 2022, 20 patients were enrolled. Median age was 56 (range 47-73). Baseline HPV positive (1,5%), HPV negative (12,60%) and HPV unknow (7,35%). TP53mut (9,45%) and TP53wt (7,35%), TP53 unknow (4,20%). PI3Kmut/amp (2,10%) and PI3Kwt (11,55%), PI3K unknow (7,35%). CPS≥20 (3,15%), CPS 1-19 (9,45%), CPS unknow (8,40%). Primary region showed that 1 patients (5%) in the oral cavity, 2 (10%) in the oropharynx, 7 patients (35%) in the larynx, 4 (20%) in the hypopharynx, 2 (10%) in the sins, 1 (5%) in the epithelial-myoepithelial and 3 (15%) in the unknown primary site. There were 16 patients (80%) with only local recurrent disease, 4 (20%) with local disease combined with distant diseases at enrollment. Median follow-up was 2 years. Adverse reactions are overall controllable (Table), but who one died with grade 4 cardiotoxicity The mPFSITT was 4.9 months, PFSmono was 4 months and PFScombination was 4.93 months (p=0.89). The mPFSITT+TP53mut was 5.1 months, mPFSITT+TP53wt was 4.6 months (p=0.63). mPFSITT+PI3Kmut/amp was 7.2 months and mPFSITT+PI3Kwt was 4.6 months. The ORRITT was 73.7% (14/19) and no complete response was achieved. The ORRcombination was 66.7% (10/15). The DCRITT and DCRcombination were all 100% . (Not included 1 died). The median OS was not reached. Conclusions: This study proves that pembro alone and combined with standard chemotherapy has good efficacy and safety in locally recurrent HNSCC, and the statuses of TP53 and PI3K may be an important factor for the prognosis of immunotherapy. Acknowledgement: Thanks MSD China Medical Affair oncology team for giving scientific support. Clinical trial information: ChiCTR2100046731 . [Table: see text]
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.
Efficacy and safety of nab-paclitaxel+cisplatin/nedaplatin + S-1 as an induction chemotherapy regimen for locally advanced hypopharyngeal cancer.
Authors: Jiang Cailing , He Xiaosong , Xu Lieyin , Xu Shengyuan , Mo Yunyan , Kang Mafei , Zhu Lin , Xue Feng
Published: June 2023

e18050

Background: Targeted therapy and immunotherapy are efficacious treatment options for advanced head and neck cancer. However, the treatment of locally advanced hypopharyngeal carcinoma still consists of surgery, radiotherapy, and chemotherapy. Combining docetaxel, cisplatin (DDP), and 5-fluorouracil as standard induction chemotherapy provided opportunities for further surgical larynx preservation in some patients. This study retrospectively analyzed the short-term efficacy and adverse events of nab-paclitaxel + DDP/nedaplatin (NDP) + S-1 as an induction chemotherapy regimen for locally advanced hypopharyngeal cancer. Methods: The study included 22 patients with locally advanced hypopharyngeal cancer treated via induction chemotherapy at the Affiliated Hospital of Guilin Medical University from December 2020 to July 2022. Among these patients, 11 received nab-paclitaxel (125mg/m2, days 1 and 8) + DDP (35- 40mg/m2, days 1-2) or NDP (65-75mg/m2, day 1) + S-1 (30-40 mg/m2 bid, days 1-14) every 21 days for a total of three cycles. A baseline enhanced magnetic resonance imaging (MRI) of the head and neck was performed for all patients to confirm the presence of suspicious lesions. Another MRI was performed before the third cycle of induction chemotherapy to confirm the efficacy of the treatment regimen. Patients, who were responsive to the induction therapy, were allowed to choose their respective sequential therapy regimen. The response was assessed using RECIST v1.1. Adverse reactions were evaluated according to CTCAE5.0. Results: The response to treatment of the 11 patients was assessed by the investigators. There was one patient with a complete response (9.1%), eight patients with a partial response (72.7%), and two patients with stable disease (18.2%). The objective response rate was 81.8% (9/11), and the disease control rate was 100%. Five of the nine patients with a partial or complete response opted for surgery after three cycles of induction chemotherapy. The pathological complete response rate was 100% (5/5). The most common grade 3 treatment-emergent adverse events (TEAE) were leukopenia (45.5%), neurotoxicity (36.3%), and anemia (18.2%). Grade 4/5 TEAEs were not observed. Conclusions: Based on the results of this retrospective study, the nab-paclitaxel + DDP/ NDP + S-1 was a safe and viable induction chemotherapy regimen for locally advanced hypopharyngeal cancer. It allowed more options for subsequent treatment. Further research is warranted to validate the findings of this study. [Table: see text]
Comparing the role of different treatment modalities in locoregionally advanced olfactory neuroblastoma: The 20-year clinical experience of a single institution.
Authors: Chai Yue , Wei Yu-Ce , Zhang Di , Dong Mei
Published: June 2023

e18055

Background: There are few studies on different treatment modalities, especially systemic chemotherapy (CT) for locoregionally advanced olfactory neuroblastoma (LA ONB) with only a few small-sample studies reported. We retrospectively analyzed the treatment patterns and explored the factors affecting the prognosis of patients with LA ONB at our center over the past 20 years in the present study. Methods: LA ONB patients from 2000 to 2020 at our center were collected retrospectively. The entire cohort was divided into combined systemic and local therapy (CSLT) vs. local therapy (LT) groups (grouping method 1), and the same cohort was divided into neoadjuvant chemotherapy (NAC) vs. non-NAC groups (grouping method 2). CSLT group included patients treated with CT + LT. LT group included patients treated with surgery (SG), radiotherapy (RT), concurrent chemoradiotherapy (CCRT), or any combination of the above methods. LT group was further divided into mono-modality local therapy (MOLT) group and multi-modality local therapy (MULT) group. MOLT group included patients treated with RT alone or SG alone. MULT group included patients treated with SG + RT/CCRT, or CCRT alone. NAC group included patients treated with NAC + LT ± adjuvant chemotherapy (ADC). Non-NAC group included patients who received LT ± ADC. Results: A total of 111 patients with LA ONB were included. The median age was 40 (range, 10–82) years old. The median follow-up duration for the entire cohort was 80.2 (range, 2.1-254.9) months, while 88.5 (range, 4.0-240.7) months for the CSLT group, 77.2 (range, 2.1-254.9) months for the LT group, 86.0 (range, 4.0-240.7) months for the NAC group, and 78.7 (range, 2.1-254.9) months for the non-NAC group. Thirty-five patients (31.5%) died, among which 30 patients died of tumor progression, 3 patients died of other diseases, and 2 patients’ causes of death were not available. The estimated 5-year overall survival (OS), progression-free survival (PFS), local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) rates for the entire cohort (n = 111) were 70.2%, 53.1%, 73.6%, and 74.1%, respectively. The estimated 10-year OS, PFS, LRFS, and DMFS rates were 61.3%, 37.7%, 60.1%, and 68.0%, respectively. In univariate analysis, patients treated with NAC (n = 43) had significantly better overall survival (OS) compared with those without NAC (n = 68) ( P = 0.041). Patients in MULT group (n = 45) had significantly improved OS ( P = 0.004) and PFS ( P = 0.003) compared with those in MOLT group (n = 15). Multivariate analysis identified NAC and CSLT (n = 51) were independent prognostic factors for superior OS ( P = 0.020; P = 0.046). Conclusions: Our study suggested that CSLT, especially a combination of NAC and LT, improved the survival of patients with LA ONB. Multiple treatment modalities yielded better PFS and OS compared to single modality treatment.
Neoadjuvant camrelizumab plus chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: A single-arm, phase II trial.
Authors: Gao Jin , Qian Liting , Zhou Lingran , Sun Bin , He Jian , Wang Ru , Zhang Yangyang , Yang Liping , Zhou Yan , Yang Jing
Published: June 2023

e18057

Background: Anti-programmed death receptor-1 (PD-1) agents improve survival in patients with recurrent or metastatic nasopharyngeal carcinoma (NPC), but have not been studied well in patients with locoregionally advanced NPC. In this study, we investigated the efficacy and safety of the PD-1 inhibitor camrelizumab combined with gemcitabine and cisplatin as neoadjuvant therapy in patients with locoregionally advanced NPC. Methods: This was a single-arm, single-center, phase II trial done at the First Affiliated Hospital of University of Science and Technology of China. Patients with previously untreated, stage III-IVB (except T3N0-1; AJCC 8th) NPC, aged 18-70 years without severe comorbidities were enrolled. Eligible patients received neoadjuvant therapy with camrelizumab 200 mg on day 1, cisplatin 80 mg/m2 on day 1, and gemcitabine 1,000 mg/m2 on days 1 and 8 of each 21-day cycle for three cycles. The primary endpoints were overall response rate(ORR) per RECIST version 1.1 and safety. Biomarker analysis included programmed death-ligand 1 (PD-L1) expression using the tumor proportion score (TPS) and combined positive score (CPS; Dako 22C3 pharmDx assay). Results: Between January 2022 and January 2023, 14 patients were enrolled and treated. The median age was 55 years (range, 33-68), and 11 (78.6%) patients were males. Thirteen (92.9%) patients had baseline PD-L1 data: TPS ranged from 2% to 80% and CPS ranged from 5 to 90. Eight patients (61.5%) had PD-L1 TPS of higher than 20% and seven patients (53.8%) had PD-L1 CPS of higher than 50. The ORR was 92.9% (13 of 14), including one (7.14%) patient with complete response and 12 (85.7%) patients with partial response. The most common grade 3 treatment-related adverse events (TRAEs; Common Terminology Criteria for Adverse Events, version 5.0) during neoadjuvant treatment were anorexia (two of 14;16.7%) and nausea (two, 9.5%), and no grade 4 or 5 TRAEs occurred. The most common immune-related AEs were endocrinopathies (all grade 1; 50%). Conclusions: Neoadjuvant camrelizumab plus chemotherapy showed promising activity with a manageable safety profile for patients with locoregionally advanced NPC. Longer follow-up and larger studies are needed to further confirm the efficacy of this combination in this population. This trial was approved by the Ethics Office of the First Affiliated Hospital of the University of Science and Technology of China (2021 no98), and registered in the Chinese Clinical Trial Registry. Clinical trial information: ChiCTR2200057745 .
Efficacy and safety of induction chemotherapy with docetaxel + cisplatin in selected groups of patients with HNSCC.
Authors: Kutukova Svetlana , Ivaskova Julia V. , Belyak Natalia P. , Varankina Anna , Androsova Alexandra , Razumova Alexandra
Published: June 2023

e18059

Background: We investigated the efficacy and safety of docetaxel + cisplatin (DC) induction chemotherapy vs TPF in patients with locally advanced HNSCC. Methods: Under our observation there were 22 patients in HNSCC (63,6% men and 36,4% women, aged 43 to 74 years (58.7±9.4 (95% CI 55.0-62.4)). The control group consisted of 18 patients (72,2% men and 27,8% women, aged 43 to 73 years (53.9±8.8 (95% CI 49.6-58.3). Both groups were comparable in terms of location, stage (III-IVA) and tumor differentiation. The patients of group 1 received DC (docetaxel 75 mg/m2 + cisplatin 75 mg/m2; q3w) as induction chemotherapy (ICT), while patients in the control group received TPF. Results: The planned number of ICT cycles (No. 3) in group 1 was received by 100% pts. and in the control group - 77.78% pts. (p = 0.02). At the control assessment according to RECIST 1.1, PR was registered in 77.3% pts. of group 1 vs 55.5% pts. in control group (p = 0.14), SD - in 22.7% vs 33.3: (p = 0.45), PD was registered only in patients of the control group - in 11.2% (p = 0.11). The frequency of registration of AEs: diarrhea gr.1-3 - 9.1% pts. group 1 vs 33.3% of pts. the control group (p = 0.06), nausea gr.1 -2 - 9.1% vs 22.2% (p= 0.25), asthenia gr. 1-2 - 4.5% versus 16.7% (p = 0.20), anemia gr. 1-2 - 9.1% vs. 16.7% (p = 0.47), neutropenia gr. 3-4– 4.5% versus 16.7% (p = 0.20). Reduction of doses of cytostatic up to 50% was performed in 4.5% pts. in group 1 and 16.7% pts. in the control group (p = 0.20). Conclusions: Induction chemotherapy in DC mode may be an effective and safe regimen in certain groups of patients with HNCH (for example, in patients with contraindications to 5-FU infusions, as well as in patients with high-risk HHNH for alternative surgical treatment or concurrent CRT as initial treatment of localized and locally advanced HNSCC.