bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of systemic treatments for patients with recurrent/metastatic head and neck squamous cell carcinoma: A systematic review and network meta-analysis.
Authors: Meng Lingbin , Ji Rui , Wang Huanhuan , Jiang Xin 
Published: June 2021

e18001 Background: A variety of systemic chemotherapy regimens have been used for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, most guidelines were derived from a single clinical trial, and no studies have comprehensively compared their efficacy and safety. This study is aimed to compare the efficacy and safety of systemic chemotherapies for patients with R/M HNSCC. Methods: We conducted a systematic review of published studies in PubMed, Embase, Web of Science, and Cochrane Library databases up to July 31, 2020. Studies were included if they were randomized controlled clinical trials including treatment regimens recommended by the latest NCCN guidelines. Eligible studies should report at least one of the following outcomes: overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and ≥3 adverse events rate (AEs). Literature screening, data extraction and quality assessment were independently conducted by two researchers. Disputes were settled by a panel of other researchers. Network meta-analysis was used to compare the efficacy and safety of various treatment regimens. Heterogeneity and consistency using the Bayesian model were evaluated in the network meta-analysis. Results: Eighteen eligible trials involving 4930 patients and 15 treatment regimens were included. Cetuximab/platinum/5-FU regimen showed higher ORR values than the following agents, including cisplatin/5-FU (odds ratio 2.96, 95% credible interval 1.42 to 6.15), cisplatin (5.43, 1.90-15.54), 5-FU (8.12, 2.22-29.61), methotrexate (8.25, 2.86-23.79), cetuximab (10.16, 1.44-71.48), and afatinib (3.64, 1.00-13.32). Immunotherapy regimens pembrolizumab/platinum/5-FU and pembrolizumab alone also showed significantly higher ORR values than these agents, while nivolumab alone showed higher ORR than the single agents. However, no significant difference was observed between Cetuximab/platinum/5-FU and pembrolizumab/platinum/5-FU. Regarding ≥3 AEs, cisplatin/paclitaxel caused the highest toxicity. No significant difference was observed on OS and PFS among all these treatment regimens. Conclusions: Cetuximab/platinum/5-FU, pembrolizumab/platinum/5-FU or pembrolizumab alone displayed high ORR with low AE rate. Nivolumab also showed better efficacy than other single agents. Although it was reported that pembrolizumab/platinum/5-FU showed better efficacy than cetuximab/platinum/5-FU, we did not find a statistically significant improvement in ORR, OS or PFS when comparing the two regimens. Therefore, further prospective trials comparing these treatment regimens remain warranted.
Identification of factors related to immunotherapy prognosis in patients with advanced head and neck squamous cell carcinoma.
Authors: Zhang Lin , Xu Xuanli , Ren Dandan , Wu Lijia , Gong Xiaoli , Li Rongrong , Zhu Guopei 
Published: June 2021

e18003 Background: Head and neck squamous cell carcinoma (HNSCC) is often diagnosed at an advanced stage and has a dismal prognosis. Anti-PD1/PD-L1 checkpoint inhibitors have shown survival benefit for the treatment on HNSCC, and are better tolerated than chemotherapy. Unfortunately, the response rate of immunotherapy is low for advanced HNSCC. Therefore, the identification of predictive biomarkers of response to anti-PD1/PD-L1 is a key point for better selecting patients that would benefit from immunotherapy. Methods: The present study included 44 patients with advanced HNSCC who received anti-PD-1 immunotherapy. Follow-up was available for them. Primary tumor tissues and matched blood samples were collected. Genome profiles were analyzed using a designed 543-gene panel based on NGS, and were available on 39 of 44 patients. Profiles of infiltrating immune cells were available for 44 patients. The infiltrating intensity of PD-1, PD-L1, CD8, CD68 and CD57 positive cells were assessed by multiplex immunohistochemistry. Results: The most frequently mutated genes were TP53 (79%), CDKN2A (33%), NOTCH1 (21%), CASP8 (13%) and PIK3CA (10%). Patients with mutations in the PI3K pathway showed a trend of longer OS (P = 0.06). Moreover, the TMB-high group showed significant superior OS than the TMB-low group (p = 0.0018). PD-L1 expression was positively correlated with CD8 expression within stroma, and PD-1 expression correlated significantly with PD-L1 and CD8 expression within both tumor and stroma areas. In addition, tumor/stromal PD-L1 and PD-1 expression were both associated with better OS (P < 0.05). Prolonged OS was also observed in patients with more tumor and stromal infiltration of CD8+ cells, CD8+PD-L1+ cells, CD68+ macrophages, or nature killer (NK, CD57+) cells. Conclusions: Higher TMB, PD-L1 expression, as well as the infiltration of immune cells within both tumor and stromal area might serve as favorable prognostic markers in advanced HNSCC patients treated with anti-PD-1 immunotherapy.
Survival results of phase I dose escalation of stereotactic body radiation therapy and concurrent cisplatin for re-irradiation of unresectable, recurrent head and neck squamous cell carcinoma.
Authors: Echevarria Michelle , Chung Christine H. , Kirtane Kedar , Muzaffar Jameel , Kish Julie Ann , Arrington John , Farinhas Joaquim , Caudell Jimmy J. 
Published: June 2021

e18020 Background: Stereotactic body radiation therapy (SBRT) is a standard option for re-irradiation of recurrent or second primary cancers of the head and neck. We conducted performed a phase I clinical trial to establish a maximum tolerated dose of SBRT with concurrent cisplatin. We previously reported our safety data, and now present our secondary disease control endpoints. Methods: Major inclusion criteria were recurrence of previous squamous cell carcinoma of the head and neck in patients who had previously undergone radiotherapy to doses ≥ 45 Gy to the area of recurrence, ≥ 6 months prior to enrollment, and who were medically unfit for surgery, deemed unresectable, or refused surgery. Patients were treated with radiation therapy every other day for five fractions at three dose levels: 30 Gy, 35 Gy, and 40 Gy. Cisplatin was given prior to every SBRT fraction at a dose of 15 mg/m2. Secondary end points reported herein are locoregional control (LRC), freedom from distant metastasis (FFDM), and overall survival (OS). Results: Twenty patients were enrolled and of those 18 patients were evaluable for secondary endpoints. Nine patients had a primary tumor in the oropharynx, four patients in the oral cavity, three in the neck, one in the larynx, and one simultaneously in the larynx and neck. All patients received the planned dose of Cisplatin. Five patients received a radiation dose of 30 Gy, three patients received a dose of 35 Gy, and 9 patients received a dose of 40 Gy. Median gross tumor volume (GTV) was 11.725 cm3. With a median follow up of 9 months the 1-year OS was 38.9%. LRC at 1 year was 45.7% and FFDM at 1 year was 87.8%. There was a trend to improved OS with increasing SBRT dose, 40 Gy vs < 40 Gy (p = 0.08). There was an improved 1-year OS with a GTV ≤11.725 cm3 of 77.8% vs 0% for tumors > 11.725 cm3 (p < 0.001). For patients with a GTV < 11.725 cm3 who received 40 Gy the 1 year OS was 100% compared with 0% for tumors larger than 11.725 cm3. Conclusions: For patients with previously radiated locally or regionally recurrent head and neck cancer, SBRT up to 40 Gy given concurrently with cisplatin provides reasonable locoregional control and overall survival for patients with smaller tumors. Further evaluation in prospective trials is warranted. Clinical trial information: NCT02158234.
Molecular profiling and survival outcomes of p16+ compared to p16- oropharynx squamous cell cancer patients.
Authors: Hughes Brittany Nicole , Shaikh Hira Ghazal , McGrath Julie Elaine , Xiu Joanne , Sukari Ammar , Korn Wolfgang Michael , Nabhan Chadi , Grover Punita , Darabi Sourat , Chernock Rebecca , Ikpeazu Chukwuemeka , Wise-Draper Trisha Michel 
Published: June 2021

e18026 Background: Previous studies have consistently shown that p16+ oropharynx squamous cell cancer (OPSCC) patients have better outcomes. The significance of molecular and transcriptional signatures and its correlation with p16 expression remains unclear. Methods: We queried the Caris Life Sciences database to assess the molecular and transcriptional signatures related to p16+ and p16- head and neck squamous cell cancer (HNSCC) patients. Comprehensive molecular profiling including whole exome sequencing (WES), targeted Next-Generation Sequencing (NGS), and immunohistochemistry (IHC) 22c3 for PD-L1 was performed (CPS ≥1 considered positive) (Caris Life Sciences, Phoenix, AZ). Tumor mutational burden (TMB) was calculated based on somatic nonsynonymous missense mutations. A standard cut-off of 2+, > 70% p16 staining was used. HPV16/18 was tested using WES. Patients were considered smokers if they had > 15 pack-years. Real world overall survival (rwOS) was obtained from insurance claims data and Kaplan-Meier estimates were calculated from the date of start of treatment to the date of last contact. Results: 948 cases of OPSCC were identified in the Caris database. 41% (82/199) were smokers. Where p16 and HPV data was available, 41% were p16+ (171/420) while HPV positivity rate was 52% (71/148). We noted a small number of patients with discordant p16 and HPV status (7 p16+/HPV-, 8 p16-/HPV+) in 327 patients who had HPV status available. Most common mutations were TP53 (33%), PIK3CA (17%) and KMT2D (10.6%). 87% were PD-L1 positive (342/394), with high expression in both p16+ and p16- subgroups, 90% and 85% respectively. 10% had TMB≥10/Mb (48/463). TP53 mutations were more common in p16- (49%) tumors in contrast to p16+ (10%) (p < 0.0005), while no statistical difference was detected in TMB≥10/Mb between the groups. CDKN2A, TERT and NOTCH1 mutations were more prevalent in tumors that were p16- or HPV- in contrast to tumors that were p16+ or HPV+ (p < 0.05). FGF3, CCND1, FGF4, FGF19 copy number alterations (CNA) were less common in p16+ OPSCC compared to p16- or HPV16- OPSCC (p < 0.0005). P16+ patients had longer rwOS when compared to p16-, 47 months versus 20 months (HR = 0.55, p = 0.014) respectively. Conclusions: Higher frequency of CDKN2A, TERT and NOTCH1 mutations among p16- (versus p16+) raise the possibility of potential targets for treatment in this group with poor prognosis. However, it remains unclear if these can serve as independent predictors of survival.[Table: see text]
Adjuvant radiotherapy plus systemic chemotherapy in resected head and neck mucosal melanoma.
Authors: Duan Rong , Tang Bixia , Chi Zhihong , Cui Chuanliang , Lian Bin , Li Siming , Mao Lili , Yan Xieqiao , Wang Xuan , Bai Xue , Zhou Li , Wei Xiaoting , Guo Jun , Sheng Xinan 
Published: June 2021

e18042 Background: The median over survival (OS) of resected head and neck mucosal melanoma (HNMM) is 49.0 months. About 65% of patients experience local recurrence or distant metastasis after surgery. Therefore, adjuvant therapy is critical to improve the poor prognosis. Methods: Data regarding HNMMs with radical surgery (stage III-IVa, AJCC HNMM 8th version) between September 1, 2006 and February 28, 2020 at Peking University Cancer Hospital was collected retrospectively. Postoperative radiotherapy was usually prescribed as GTV 60-70Gy/CTV 60Gy/30f. Patients were divided into four groups by the adjuvant regimens: radiotherapy+chemotherapy (RC), chemotherapy (C), radiotherapy (R) and observation (O). Results: In total, 368 patients were enrolled, including 104 RC,114 C, 53 R, 97 O, respectively. After median follow-up of 63.9 mo (range: 0.9-146.7), the median local relapse-free survival (LRFS) was 10.1 mo (95%CI: 6.7-13.6) in the O group, as compared with 65.9 mo (95%CI: 31.7-100.1, P＜0.001) in the R group, 75.6 mo (95%CI: 50.1-101.0, P＜0.001) in the C group, and 84.6 mo (95%CI: 48.5-120.8, P＜0.001) in the RC group. The median distant metastasis-free survival (DMFS) was 13.7 mo (95%CI: 8.0-19.5) in the O group, 15.3 mo (95%CI: 8.7-21.9, P = 0.898) in the R group, as compared with 25.7 mo (95%CI: 14.6-36.8, P = 0.001) in the C group, 49.3 mo (95%CI: 32.6-66.0, P＜0.001) in the RC group. Estimated OS was 36.4 mo (95%CI: 24.0-48.8) in the O group, as compared with 30.8 mo (95%CI: 23.0-38.6, P = 0.733) in the R group, 40.8 mo (95%CI: 34.8-46.8, P = 0.289) in the C group, 58.2 mp (95%CI: 36.4-79.9, P = 0.002) in the RC group. Primary location, age, gender, UICC staging and adjuvant regimens were included for multivariate Cox analysis. With regard to OS, UICC stage and RC were the prognostic factors. With regard to DMFS, UICC stage, RC and C were the prognostic factors. With regard to LRFS, UICC stage, RC, R, C were the prognostic factors. Conclusions: It is the largest study on the role of adjuvant radiotherapy and chemotherapy on HNMM till now. The results demonstrate that postoperative radiotherapy improves LRFS but has no impact on DMFS, while adjuvant radiotherapy plus chemotherapy prolongs OS. It further validates the clinical practice of UICC stage of HNMM, which might shed lights on the study of the whole mucosal melanoma.
Access to radiation oncology centers with brain tumor treatment expertise for patients with resectable brain tumors.
Authors: Choi Mehee , Martin Brian P. , Misell Lisa , Zabramski Joseph M. , Brachman David G. 
Published: June 2021

e18509 Background: Many patients with brain tumors face challenges with access to care. For rural patients, prolonged travel times may limit access to appropriate radiotherapy. Radiation centers (RCs) offering specialized brain radiotherapy, e.g., stereotactic radiosurgery (SRS), are geographically limited. Utilization of brain brachytherapy at the time of resection offers an option for such patients, but technical challenges have limited the adoption. To address the limitations of traditional brachytherapy, a device with Cs-131 seeds embedded in a bioresorbable collagen tile (GammaTile, GT Medical Technologies, Tempe, AZ USA) was developed. GammaTile (GT) is FDA-cleared for permanent implantation at the time of resection for all recurrent intracranial tumors and for newly diagnosed malignant intracranial neoplasms. To investigate if wider availability of this treatment could possibly lower the geographic barrier to access to care, we mapped the US population against existing RCs with brain tumor expertise and neurosurgery centers (NSCs) performing craniotomies. Methods: We analyzed 2018 CMS claims data using CPT codes for single- and multi-fraction SRS to identify RCs with brain tumor treatment expertise and mapped these against the population. Using similar methodology, using CPT codes for craniotomies, we identified NSCs, as any facility performing craniotomies is potentially eligible to implant GT. Results: 135 RCs used CPT codes for SRS. 193-, 119-, 82-, and 52-million Americans lived >30-, >60-, >90-, and >120-minutes from one of these centers, respectively. 530 NSCs preform craniotomies, including ≥1 in every state, a 4-fold increase over the number of RCs offering SRS. Conclusions: For many patients, substantial travel distances limit their access to RCs with brain tumor treatment expertise. In contrast, the 530 craniotomy-performing NSCs have far greater geographic dispersion. The option of undergoing brain radiation with GT implantation at the time of brain tumor craniotomy brings treatment closer to millions, ensures compliance, and reduces additional travel for follow-up radiation treatment.[Table: see text]
Comparison of care process for newly diagnosed breast cancer in insured versus uninsured populations: Opportunities for improving health equity.
Authors: Botrus Gehan , Ertz-Archambault Natalie , Nafissi Nellie , Gonzalez Velez Miguel , Kosiorek Heidi E. , Ernst Brenda , Northfelt Donald W. 
Published: June 2021

e18518 Background: Initiatives enhancing equitable oncologic care are an increasingly emphasized priority. Our study aims to identify aspects of breast cancer (BC) care in which differences exist based on insurance coverage status. Methods: We performed a retrospective, case control study consisting of 39 Hispanic ethnicity uninsured patients (UP) with newly diagnosed BC at federally qualified health centers and 119 insured patients (IP) diagnosed at Mayo Clinic Arizona (MCA). Patients were matched 3:1 for age, stage, year of diagnosis, ER and HER2 status. Demographic information, clinical variables, and zip code level specific socioeconomic information were compared. Continuous variables were compared by Wilcoxon rank-sum test and categorical variables by chi-square test. All patients ultimately received their cancer treatment at MCA. Results: Similar treatment patterns with chemotherapy, surgery, and radiation treatment were observed between groups. Primary language was Spanish for 94% of UP and English for 97.5% of IP. The majority of UP were of Hispanic ethnicity (97.4%); IP were 83.2% non-Hispanic White, 9.2% Hispanic, 3.4% African American. Zip code level information reflected more unemployment with a median of 10.6% versus 6.9% p ˂ 0.001, percent of high school or lower (53.0 % v 23.2 %, p ˂ 0.001), and lower income for UP (33733.5 v 64728.0 p values ˂ 0.001). UP BMI was significantly higher (30.6 V 24.7, p=0.005), with presence of more co-morbidities; diabetes (28.2% v 5.0%, p ˂ 0.001), hypertension (35.9 % v 20.2%, p= 0.046), dyslipidemia (28.2% v 12.6%, p = 0.023), metabolic syndrome (p 23.7% v 8.5, p= 0.013), and tobacco use (17.9% v 2.5%, p ˂ 0.001). IP had higher alcohol use (52.9% v 5.3%, p ˂ 0.001). Genetics consultation was performed for 62.2% IP versus 35.9% UP (p=0.004), lower acceptance of oncology nutrition consultation for UP (29.4% vs 7.4%, p= 0.024) Median time from abnormal mammogram to biopsy (25.5 days vs. 14 days, p=0.056), and interval from diagnosis to treatment (62 days vs. 39 days) (p=0.001) were less favorable for UP compared to IP. Conclusions: In comparing the status of UP (primarily Hispanic, Spanish-speaking) and IP (primarily non-Hispanic White, English-speaking) with newly diagnosed BC we identified greater prevalence of co-morbidities and adverse social determinants of health in the former group. We identified access to genetic counseling services, access to oncology nutrition consultation, and timeliness of diagnostic biopsy and initiation of treatment as disparate features in the care pathway. These observations can allow development of tailored interventions to achieve greater equity in delivery of BC care.
Disparities in breast cancer by race and ethnicity.
Authors: Warrior Surbhi , Rao Ruta D. 
Published: June 2021

e18526 Background: Breast cancer is the most common female malignancy. While there have been significant advances in diagnosis and treatment of breast cancer, there are gaps in care leading to high mortality rates in low socio-economic populations and ethnic minorities. This inequality is attributed to poor access to care and later stages at diagnosis. Methods: All female breast cancer patients between 2000-2020 (N=8,444) were included. Statistical analysis was done with X2 testing for categorical variables and T-tests for continuous variables. A univariate logistic regression was used to understand impact of each characteristic. Results: Black women were more likely to have poor prognostic factors for breast cancer compared to white women: distant metastatic disease at diagnosis (4.6% vs 3.2%, p=0.02), triple negative disease (25% vs 13.6%, p<0.01), high oncotype dx score >25 (37.2% vs 26.1%, p=0.04), recurrence (14.9% vs 12.1%, p=0.04), and mortality rate (24.2% vs 15.6%, p<0.01). Despite these high-risk factors, white women were more likely to have a mastectomy than black women (43.8% vs 35.4%, p<0.01), and the average age at diagnosis was higher in black women at 59.2±13.5 years compared to white women at 57.5±12.8 years (p<0.01). The most prominent poor prognostic factor in black women was having triple negative breast cancer with OR 2.13 (95% CI 1.7- 2.6) compared to others in Table. Hispanic women were more likely to have higher stage at diagnosis (OR 1.21), lymph node involvement (OR 1.03), metastatic disease (OR 1.43), and tumor size >1cm (OR 1.06) than nonHispanic women, but only lymph node involvement at diagnosis was statistically significant (29.1% vs 24.5%, p=0.02). Conclusions: There is a high prevalence of racial and ethnic disparities in women with breast cancer. Black women are more likely to have poor prognostic factors including metastatic disease at diagnosis and triple negative breast cancer, leading to higher recurrence and mortality rates. Hispanic women are also more likely to have poor prognostic factors, but this data was not statistically significant due to small sample size. Efforts to improve access to health care leading to earlier diagnosis may decrease the gap in mortality rate for minority women with predisposition to high-risk malignancies.[Table: see text]
Outcome disparities in rural versus urban patients with head and neck cancer: Leveling the playing field.
Authors: Kaur Varinder , Rooney Anthony , Desai Raj Piyush 
Published: June 2021

e18529 Background: Multiple studies indicate that rural patients experience disproportionately adverse cancer related outcomes, compared to their urban counterparts. This has been attributed to inequities in access to healthcare, monetary and technological resources, disease characteristics, adverse health status and lower life expectancy of rural populace. Whether treating patients with uniform protocols can help mitigate outcome disparities remains to be determined. Methods: We conducted a retrospective cohort study to evaluate survival outcomes of Head-Neck Squamous Cell Cancer (HNSCC) patients from rural versus urban locales. Only patients with locally advanced HNSCC who completed radiotherapy (RT) at the Emily Couric Clinical Cancer Center were included. Rural patients had access to affordable lodging for the duration of radiotherapy (RT), were treated regardless of health insurance status and by the same multidisciplinary team. Patients with distant metastases were excluded. Patients were classified as urban or rural using the Rural-Urban Commuting Areas (RUCA) zip-code database. Overall survival (OS) was analyzed using Kaplan-Meier curves and log-rank test. OS was modeled with a COX proportional hazards model, adjusting for several covariates including race, age, gender, HPV status, smoking, treatment received (RT, chemotherapy, surgery) and stage. Results: 230 patients with Stage I-IVB HNSCC who met the inclusion criteria were analyzed, of which 136 were categorized as residentially urban and 94 were categorized as rural. Approximately 83% were male, 87% were Caucasian and 71% were smokers (52% current smokers and 19% former smokers). In addition to RT, 42% patients had undergone surgery and 57% received chemotherapy. There was no statistically significant difference in OS for patients residing in rural vs urban zip-codes (HR 1.36, p = 0.24). Rural patients were less likely to undergo surgery (34% vs 44%, p = 0.04), and more likely to receive chemotherapy (67% vs 54%, p = 0.0325), likely indicating more advanced tumor stage at diagnosis. Conclusions: Rural and urban patients had similar OS when treated with similar treatment protocols. Improving access to uniform treatment regimens may help mitigate the widening gap in cancer-related outcomes between rural and urban populations.