bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nomogram to predict duration of clinical benefit from nivolumab in platinum resistant, recurrent/metastatic head and neck squamous cell carcinoma.
Authors: Feeney Laura , Rack Samuel , Mistry Hitesh , Bola Becky , McPartlin Andrew , Sykes Andrew , Metcalf Robert 
Published: June 2022

e18016 Background: Immune checkpoint blockade of the programmed death-1 receptor (PD1) with nivolumab improves survival for patients with platinum resistant recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, response rates are only 15-20% and the majority of patients do not have prolonged clinical benefit. Established predictive biomarkers such as PDL1 are not reliable in this context and there remain no reliable predictors of response to nivolumab in R/M HNSCC. We therefore sought to evaluate a panel of clinical, haematology and biochemistry parameters to develop a nomogram to predict the duration of clinical benefit following treatment with nivolumab. Methods: Ninety-one patients treated with nivolumab for R/M HNSCC were included. Nivolumab was administered as standard of care management and tumour response was evaluated every 8-12 weeks using CT or MRI. The electronic clinical records were reviewed and all clinical and demographic data were extracted in addition to baseline haematology and clinical biochemistry values. Using Cox proportional hazard analysis these variables were used to create a predictive model for duration of clinical benefit. Patients were dichotomised based upon duration on nivolumab treatment. Backwards elimination with a p-value threshold of 0.05 was used to create a predictive nomogram. For the final model, patients were assigned to two groups (< 3 months and ≥ 3 months on therapy) calculated from the date of first nivolumab dose to the date of discontinuation. Progression free survival (PFS) and overall survival (OS) were calculated from the date of the first dose of nivolumab. Results: Of the 91 patients, 82 had stopped treatment at the time of analysis with a median time on treatment of 2.5 months (95% CI 1.8 to 3.6). Median PFS was 3 months with 1-year PFS rate of 15%. Median OS was 9 months with 1 year OS rate of 40%. Multivariable analysis identified multiple pre-treatment factors that correlate with time on treatment; age (HR 0.97; 95% CI 0.93-1.00, p = 0.029), oropharyngeal tumour location (HR 0.51; 95% CI 0.31-0.85, p = 0.01), N stage (HR 1.84; 95% CI 0.97-3.5, p = 0.061), M stage (HR 2.44; 95% CI 1.27-4.7, p = 0.007), and pre-treatment peripheral blood markers which included monocyte count (HR 2.83; 95% CI 1.05-7.6, p = 0.04), sodium (HR 0.94; 95% CI 0.88-1.00, p = 0.057) and calcium (HR 7.6; 95% CI 1.46-39.7, p = 0.016) levels. These were included in the final nomogram which had a concordance index of 0.69. Conclusions: We have developed a novel nomogram to predict the duration of clinical benefit from nivolumab in platinum resistant R/M HNSCC for subsequent independent validation. This may assist clinicians in counselling patients and clinical decision making and could also be used to identifying poor responders for whom alternative treatment options are required.
Factors associated with recurrence in oral cavity squamous cell carcinoma: A real-world experience from an Indian comprehensive cancer center.
Authors: Sood Siddharth , Mehta Prashant , Sharma Sakshi , Badola Amit 
Published: June 2022

e18018 Background: Oral cavity squamous cell carcinoma (OCSCC) is the third most common malignancies in India with an estimated 72,000 deaths annually. The incidence is increasing owing to rising alcohol and tobacco consumption in last 2 decades. Methods: We performed a retrospective cohort study in patients with OCSCC to identify risk factors for local and metastatic recurrences following definitive treatment including surgery and/or radiation therapy or chemotherapy or both at our institute. Patient records were screened from 2016 till 2021. Eligible patients were followed up for disease status and outcome. Data included sociodemographic details, substance use, tumor differentiation, stage at diagnosis, LVI, PNI, margin status, treatment details and site of recurrence. All statistical analysis was performed on Microsoft excel 2016 and Jamovi version 1.6.23.0. Results: Out of 195 patients files screened, 90 were available for analysis. Demographic details, substance use pattern and tumor profile are highlighted in table. Tongue was the most frequent site involved and most of the tumors were well to moderately differentiated. Majority of the patients presented as locally advanced disease (Stage IVa). LVI and PNI were identified in 5.75% and 29.89% patients respectively while one of the patients had a positive margin after resection. Surgery followed by adjuvant chemo-radiation was the most frequently prescribed treatment (n = 46; 52.8%) whereas 27.59% patients (n = 24) underwent surgery alone. Fifty six (63.3%) patients experienced recurrence out of which 50% were local and 35% were metastatic recurrences. On multivariate analysis, the predictors of disease recurrence were male gender (OR- 3.2; 95% CI- 1.02-10.05; p-0.05), tobacco and alcohol use (OR- 1.93; 95% CI- 0.8-4.6; p- 0.14 and OR- 2.16; 95% CI- 0.82-5.65; p- 0.12 respectively), Stage IVb disease (OR- > 10; 95% CI- 0-10; p-1.0), presence of PNI (OR- 1.39 ; 95% CI- 0.55-3.70; p-0.497) and presence of LVI (OR- 2.54; 95% CI- 0.36-50.8; p- 0.414). Median disease free survival and overall survival of the cohort was 11.3 months and 15 months respectively. Advanced stage, tobacco consumption, presence of LVI and PNI negatively affected overall survival in our cohort. Conclusions: Oral cavity squamous cell carcinoma is among the most preventable malignancies and they contribute to significant morbidity and mortality. This study highlights the role of early detection and management of such patients. Patients may still experience disease recurrence after initial management which may be difficult to treat. Such patients should be encouraged to participate in a clinical trial as treatment options for recurrent disease are limited.[Table: see text]
Efficacy and tolerability of a low dose weekly paclitaxel, carboplatin, cetuximab (PCC) regimen for metastatic or unresectable head and neck squamous cell carcinomas.
Authors: Locke Margaret , Kohn Nina , Seetharamu Nagashree 
Published: June 2022

e18019 Background: The standard of care for metastatic or unresectable head and neck squamous cell cancers (HNSCCs) is 5-FU and a platinum doublet with cetuximab or pembrolizumab. However, these regimens are cumbersome as they involve hospitalization for continuous 5-FU infusion and carry a high toxicity profile. In addition, many patients are unfit for this regimen due to poor performance status (PS) or comorbidities. An alternative is paclitaxel, carboplatin, and cetuximab (PCC). PCC has been shown to be a promising induction regimen in small, mostly retrospective studies. Also, low dose chemotherapy may improve tolerability. Our study evaluates the tolerability and efficacy of low dose PCC with or without concurrent palliative radiation therapy (RT) in patients with metastatic or unresectable HNSCCs. Methods: This retrospective observational study included 40 patients with metastatic or unresectable HNSCCs at a single academic center who received PCC between August 2017 and January 2022. Included patients were not candidates for standard frontline therapies due to either PS, comorbidities, prior progression on these therapies, plan for RT, or patient preference. Chart review was performed to grade adverse events (AEs) according to CTCAE criteria. Progression free survival (PFS), overall survival (OS), and response to treatment were assessed per RECIST 1.1 guidelines. Results: Of the 40 patients, mean age was 69.6 years (SD 15.4), and 82.5% were male. Common primary sites were oral (13, 32.5%), oropharynx (12, 30%), hypopharynx (4, 10%), and sinus (4, 10%). Most patients had Stage IVa disease (16, 40%) followed by IVc (12, 30%) and IVb (6, 15%). The remainder (6, 15%) had stage III or unknown stage. Patients received weekly paclitaxel (30-50 mg/m2), carboplatin (AUC 1.5-2), and cetuximab 400 mg/m2 loading followed by 250 mg/m2 maintenance dose. 8 patients (20%) received concurrent RT. Most were treated with palliative intent (32, 80%) and a few induction intent (8, 20%). Prior to PCC, 11 patients had prior salvage surgery, 19 prior RT, and 18 prior systemic therapy. Baseline ECOG PS was 0-2 in 37 patients (92.5%). The most common AEs were skin rash (27, 67.5%), fatigue (22, 55%), and mucositis (12, 30%). 7 patients (17.5%) experienced a grade 3-4 AE, which were mostly hematologic. 2 of the 8 patients on concurrent RT experienced a grade 3-4 AE. 5 patients (12.5%) stopped PCC treatment due to toxicities. 8 patients (20%) had progression on initial follow up imaging. Median duration of response was 4.3 months. PFS was 7.8 months. Median OS was 19.2 months. Conclusions: Our study supports the use of PCC in metastatic or unresectable HNSCCs. This regimen can be considered in patients with suboptimal PS who are not candidates for standard frontline therapies or for those planned for palliative RT. PCC can be used safely and effectively with or without concurrent RT.
Anlotinib for patients with recurrent or metastatic nasopharyngeal carcinoma: A phase II study.
Authors: Cai Qingqing , SU Ning , Fang Yu , Zou Qihua , Xia Yi , Ma Shuyun , Cai Jun , Liu PanPan , Wang Jinni , Zhang Yuchen 
Published: June 2022

e18020 Background: The prognosis of patients (pts) with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) is poor, especially for those who had failed two or more lines of prior systemic therapy. Anlotinib is a novel tyrosine kinase inhibitor that can inhibit tumor angiogenesis and proliferation by targeting VEGFR, FGFR, PDGFR, and c-Kit. A prospective, single-arm, phase 2 trial (NCT03906058) was performed to assess the efficacy and safety of single-agent anlotinib against R/M NPC and here we report the final results of this study. Methods: Eligible pts were aged 18-70 years old, diagnosed with histologically confirmed R/M NPC, had at least one measurable lesion and failed at least two lines of prior systemic treatments including chemotherapy, targeted therapy, or immunotherapy. Anlotinib was administered at 12 mg QD orally from day 1 to day 14 every 3 weeks until disease progression or intolerable toxicity. The primary endpoint was confirmed disease control rate (DCR). The second endpoints included confirmed objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and safety. Tumor response was assessed according to RECIST 1.1 and adverse events were assessed according to NCI-CTCAE v5.0. Results: From April 2019 to March 2021, 39 pts were enrolled. 33 were male and 6 were female. The median age was 46.7 years (range, 20-64). 24 pts (61.5%) had liver metastasis. 29 pts (74.4%) had previously received 2 lines of systemic treatments and others received 3 or more. 19 pts (48.7%) pts had been exposed to anti-PD-1 immunotherapy. The median treatment duration of anlotinib was 4 cycles (range, 0.5-20). At the data cutoff date of Feb.1st 2022, 36 pts have underwent tumor response evaluation and the best response to anlotinib was partial response for 8 pts and stable disease for 20 pts. The DCR was 77.8% and ORR was 22.2%. 28 patients have progressed. For the intent-to-treat population, the median PFS was 5.7 months (95% CI: 4.7-6.7). 21 pts have died and the median OS was 23.9 months (95% CI: 5.3-42.5). The most common treatment-related adverse event (TRAE) of any grade was hand-foot syndrome (HFS) (24 pts). Grade 3 TRAEs included HFS (9 pts), mucositis (7 pts), hypertension (21 pts), liver dysfunction (2 pts) and pneumonia (1 pts). Only one grade 4 TRAE (mucositis) was reported and no treatment-related death was observed. 13 pts experienced hemorrhage, all were grade 1 or 2. Conclusions: Anlotinib monotherapy seemed to be a promising option for pts with R/M NPC who were heavily treated. The survival benefits were impressive and the toxicity was tolerable. Clinical trial information: NCT03906058.
Long-term outcomes of phase I/II study of palliative triple metronomic chemotherapy in platinum-refractory/early failure oral cancer.
Authors: Dhumal Sachin Babanrao , Patil Vijay Maruti , Noronha Vanita , Menon Nandini Sharrel , Nawale Kavita Prakash , Mahimkar Manoj , Prabhash Kumar 
Published: June 2022

e18021 Background: Triple metronomic chemotherapy is one of the options of treatment in platinum-refractory/early failure oral cancer. However long term outcomes with this regimen are unknown. Methods: Adult patients with platinum-refractory/early failure oral cancer were enrolled in the study. Patients were administered erlotinib 150 mg once daily celecoxib 200 mg twice daily and methotrexate weekly (phase 1 in variable dose 15-6 mg/m2 & 9 mg/m2 in phase 2), all taken orally till progression of disease or development of intolerable adverse events. The primary objective was to estimate the long term overall survival and factors impacting it. Kaplan Meier method was used for time to event analysis. COX proportional hazard model was used to identify factors impacting OS and PFS. The factors included in the model were age, gender, ECOG PS, tobacco exposure, a subsite of primary and circulating endothelial cell levels at baseline. A p-value of 0.05 was considered significant. Results: A total of 91 patients were recruited (15 in phase 1 & 76 in phase 2), the median follow-up was 41 months and 84 events of death had occurred. The median OS was 6.67 months (95%CI 5.43-7.37). The 1-year, 2-years and 3-years OS were 14.07% (95%CI 7.75-22.2), 5.86% (95%CI 2.18-12.2) and 5.86% (95%CI 2.18-12.2) respectively. The only factor favourably impacting OS was the detection of circulating endothelial cells at baseline (HR = 0.459; 95%CI 0.28 -0.753, P = 0.002). The median PFS was 4.3 months (95%CI 4.1-5.1) and the 1-year PFS was 12.97% (95%CI 6.8-21.2). The factors with statistically significant impact on PFS were detection of circulating endothelial cells at baseline (HR = 0.479; 95%CI 0.3 -0.775, P = 0.002) and tobacco exposure at baseline (HR = 0.505; 95%CI 0.272 -0.937, P = 0.03). Conclusions: The long term outcomes with triple oral metronomic chemotherapy with erlotinib, methotrexate and celecoxib are unsatisfactory. Detection of circulating endothelial cells at baseline is a biomarker predicting efficacy of this therapy. Clinical trial information: CTRI/2016/04/006834..
Impacts of hepatitis b infection in patients with head and neck squamous carcinoma.
Authors: Lai Cheng-Lun , Su Yu-Chen , Lin Cheng-Hsien , Chou Cheng-wei 
Published: June 2022

e18051 Background: Hepatitis B Virus (HBV) infection was known to be have impacts of occurrence and survival in different malignancies. We aim to evaluate the clinical association with head and neck squamous cell cancer (HNSCC) and HBV infection. Methods: A retrospective review was conducted on the medical records and cancer registry database at the Taichung Veterans General Hospital (Taichung, Taiwan) between January 2007 and December 2015. Patients with histologically proven squamous cell carcinoma of oral cavity, oropharynx, hypopharynx and larynx were enrolled in the study. HBV infection was defined as HBsAg seropositivity. Clinical features, hepatic function test and five-year overall survival (OS) were compared between patients with and without HBV infection. Results: A total of 1826 HNSCC patients were analyzed. 225 of them (12.3%) were proved HBV-infected. The HBV-infected patients was diagnosed at younger age (< 65 years; 76.1% vs. 65.5%, p< 0.012) and had a higher proportion of initial liver cirrhosis (11.6% vs. 3.6%, p< 0.001) and hepatic dysfunction (10.7% vs. 6.1%, p= 0.009) included elevation of alanine transaminase (ALT), aspartate transaminase (AST) and prothrombin time expressed as international normalized ratio (INR). The other baseline characteristics were similar. The five-year OS were 52.9% and 48.6% in the HNSCC patients with or without HBV infection, respectively ( p= 0.341). The incidence of later founded hepatic dysfunction during follow-up was similar (31.1% vs 26.2%, p= 0.122). Conclusions: Information from this study indicated that HBV-infected HNSCC patients may present in younger age, more initial liver cirrhosis, and hepatic dysfunction. However, HBV infection did not have negative impacts on survival outcome and later founded hepatic dysfunction in those patients. Characteristics and survival of HBsAg (+) vs. HBsAg (-) HNSCC Patients[Table: see text]
Long-term follow-up results of the effects of chronotherapy and conventional chemotherapy combined with intensity modulated radiotherapy on dendritic cells and lymphocyte subsets in nasopharyngeal carcinoma.
Authors: Minghui Yang 
Published: June 2022

e18066 Background: In this study, we compared the effects of chronotherapy with conventional chemotherapy plus intensity modulated radiotherapy (IMRT)on dendritic cells and lymphocyte subsets in locoregionally advanced NPC. Methods: Analysis of 136 patients with treatment locoregionally advanced nasopharyngeal carcinoma enrolled, 68 patients were randomly assigned to the chronotherapy group and 68 patients to the conventional chemotherapy group, and all patients received 2-3 cycles of TPF induction chemotherapy plus 2-3 cycles of cisplatin concurrent chemoradiotherapy with the following schedules: docetaxel (DOC): 60mg / m2, ivgtt, D1 (03:30-04:30); Cisplatin (DDP): 60mg / m2, civ, d1-d5 (10:00-22:00); 5-fluorouracil (5-FU): 600mg / m2 / D 1, civ, d1-d5 (22:00-10:00); Synchronized DDP 100mg / m2, civ, D1 (10:00-22:00). Conventional group: Doc 60 mg / m2, ivgtt, D1; DDP 60mg/m2, ivgtt, d1; 5-FU 600mg/m2 /d 1, civ, d1-d5(120h); Synchronized DDP 100mg / m2, IVGTT, D1. Both groups were treated with IMRT at the same dose。 Lymphocyte and lymphocyte subsets were measured by flow cytometry before induction chemotherapy and 1 year versus 3 years after the end of concurrent chemoradiotherapy in patients, and changes in immune parameters, survival, and long-term toxicities were compared between the two groups. Results: One year after induction chemotherapy and concurrent chemoradiotherapy, the chronotherapy group showed higher plasma dendritic cells (PDC) than the conventional group (P < 0.05). At 1 year after induction chemotherapy and concurrent chemoradiotherapy, CD4 +, activated CD4 +, activated CD8 +, CD3-CD16 +, PDC, and MDC were significantly higher (P < 0.05) in both pre - and post-treatment groups, and at 1 year after induction chemotherapy and concurrent chemoradiotherapy in the conventional group (P < 0.05). At 3 years after induction chemotherapy and concurrent chemoradiotherapy, CD4 +, activated CD4 +, activated CD8 +, CD4 + CD25 +, cd3-cd19 +, and CD3-CD16 + were significantly increased in the chronic group (P < 0.05), and CD4 +, activated CD4 +, activated CD8 +, and CD4 + CD25 + were significantly increased in the conventional group (P < 0.05). In the comparison of toxic effects between the two groups, the incidences of xerostomia and dysphagia in the group at 3 years after treatment were significantly lower than those in the conventional group (P < 0.05). There were no significant differences in PFS, OS, DMFS, LRRFS between the two groups at 3 years (P > 0.05). Conclusions: Chronotherapy with intensity-modulated radiotherapy for locoregionally advanced nasopharyngeal carcinoma more than conventional chemoradiotherapy reduces damage to dendritic cells and lymphocytes and alleviates toxic effects such as xerostomia and dysphagia at the same survival rate.
Novel algorithm for assigning risk/disease-directed treatment (DDT) choice in locally advanced primary squamous cell carcinoma head and neck (SCCHN): Using pretreatment data only.
Authors: Talor Eyal , Lavin Philip T , Markovic Dusan 
Published: June 2022

e18070 Background: Locally advanced primary SCCHN, DDT options (radiotherapy (RTx) or concurrent Chemoradiotherapy (CRTx)) is performed only following surgery (National Comprehensive Cancer Network [NCCN] Guidelines). A novel 2-step exclusion algorithm was developed, based only on N classification and imaging (CT; MRI +/- PET) to detect clinical features only from screening/entry findings. The algorithm was developed using the IT-MATTERS SCCHN pivotal study (Clinical trials.gov NCT01265849) data to identify treatment naïve lower risk (LR) for recurrence subjects receiving neoadjuvant immunotherapy prior to surgery to optimize long-term overall survival (OS). Methods: SCCHN patients are routinely examined and imaged at entry/screening to establish TNM classification and disease stage. Imaging is performed using CT, MRI, and/or PET-CT/PET-MRI per NCCN Guidelines. These imaging techniques can reliably detect extracapsular cervical lymph node spread before surgery, allowing the algorithm to be constructed and validated. Algorithm rules target CRTx bound (“High-Risk”) patients leaving RTx bound (“Low-Risk”) locally advanced primary disease patients at entry. The 2-step exclusions are: (1) exclude all N2 leaving only those with N0-N1, (2) further exclude those exhibiting extra capsular spread (PET-CT or PET-MRI). We retained those determined by study physicians to receive CRTx for the algorithm validation exercise only. The n = 923 pivotal study intent to treat (ITT) population was used to validate the algorithm. Results: Overall algorithm coverage was 99.9% (922/923 ITT except one missing N case) with 24.6% having N2 and 75.3% N0/N1. Among algorithm exclusions, 81.3% (282/347) were High-Risk; among algorithm inclusions, 60.6% (349/576) were Low-Risk. Algorithm validation: Among all Low-Risk cases in the study (n = 380), 91.8% (349/380) met the algorithm criteria; among all High-Risk cases, 60.4% (282/467) were correctly excluded by the algorithm. Remaining were physician choice. Overall, algorithm alone predicted 74.5% (631/847) risk group (combined low and high) accurately. Significant OS advantage (2-sided log rank p = 0.0376) to Immunotherapy regimen + standard of care (SOC) surgery + RTx vs SOC alone was seen for Low-Risk cases selected only by the 2-step algorithm. Conclusions: The algorithm provided near perfect (99.9%) ITT population coverage, achieved near 75% overall accuracy, with 91.8% accurate predictive value for the low-risk group demonstrating significant OS. Thus, risk group can be inferred at screening consistent with clinical practice and NCCN Guidelines. The algorithm can be used to help identify low risk SCCHN patients at entry to receive neoadjuvant immunotherapy before surgery.