bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of treatment costs for pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma based on KEYNOTE-040 clinical trial.
Authors: Yeh Justin , Guddati Achuta
Published: May 2020

e18524

Background: Pembrolizumab has been approved by the FDA for the treatment of recurrent and refractory squamous cell cancer of the Head and Neck. This approval was based on the favorable results noted in the pembrolizumab arm of the KEYNOTE-040 clinical trial which compared pembrolizumab with the standard of care (methotrexate/cetuximab/docetaxel). This study aims to compare the financial aspects of these treatment arms in the setting of their relative clinical advantages in terms of increased overall survival by applying current pricing of the drugs and treatment for side effects. Methods: Data published from the KEYNOTE-040 study was used to generate a model incorporating the cost of each drug in both arms. The incidence of side effects was also extracted from the published data. The cost of treatment of side effects was extracted from previously published data and used for cost estimation in the model. The number of years added in terms of overall survival was calculated for the entire experimental arm and the cost of each such year was calculated. This model assumes that all drugs were supplied at the cost indicated at the retail price advertised by their producers. The cost was adjusted for inflation to the current year. Results: Based on current pricing, 248 patients in the control arm which involved methotrexate /cetuximab /docetaxel incurred an estimated total cost of $2,918,185 over 24 months. The total cost for the pembrolizumab arm based on current pricing was $36,744,819 for 247 patients over 24 months. The cost of management of adverse effects was $383,910 vs. $18,728 (Std. of care vs. Pembrolizumab). The total cost averaged over all patients in both arms was $13,314 vs. $ 148,840. There is an inverse relationship between drug cost and management of adverse side effects in both arms. Conclusions: Treatment with pembrolizumab confers an increase in overall survival but the cost of the incremental gain appears to be high. The model makes several assumptions including the distribution of cost over the patient population in both arms and extrapolates it to the cost in US dollars. It is very likely that the quality of life was superior in the pembrolizumab arm but it was not incorporated into our model. Justification of the continued use of pembrolizumab must be weighed against the long term survival benefits accrued by its usage in the context of a different and possibly better quality of life.
Neoantigen-based vaccination as a practical measure for head and neck cancer treatment.
Authors: Zheng Xiao-bin , Chen Chuan-ben , Chen Yu , Hao Shiguang , Jun Liu , Xiong Jia-ni , Lin Jin , Xu Yaping , Guan Yan-Fang , Li Yi , Huang Yingying , Yi Yuting , Xia Xuefeng
Published: May 2020

e18528

Background: The view that neoantigens serve as potential vaccine targets has arisen in the last decade. Clinical and computational efforts have been done to increase the practicality of its application in real world. With these advances, we conducted a retrospective study on a Chinese population to explore the clinical feasibility of neoantigen-based vaccines for head and neck cancer treatment. Methods: Tumor and normal samples were profiled using a 1021-gene panel. Sequencing data were pre-analyzed according to our in-house standard procedures. Class I HLA typing was completed using OptiType v1.0. Curated somatic mutations in coding regions (SNVs and non-frameshift Indels with an allele frequency ≥ 5%) were collected and altered peptides produced by these mutations were analyzed using NetMHCpan v4.0. Peptides with an IC50 < 500 nM were considered potential binders, and especially, those with an IC50 < 50 nM were considered strong binders. An altered peptide was considered a neoantigen if IC50 altered is < IC50 wildtype. Results: We analyzed a total of 243 patients and detected 114 unique HLA alleles. By carrier percentage, the top three alleles are C*01:02 (44%), B*46:01 (36%), and A*11:01 (33%). In total, 743 mutations were deemed eligible for neoantigen prediction and 223 unique neoantigens were found. Of these neoantigens, 67 (carried by 21% of patients) were strong binders, among which 26 (carried by 9% patients) exhibited a great fold change (≥ 5 folds) of binding affinity. Moreover, the neoantigens in these patients are unique, as only two neoantigens were shared. A search for shared neoantigens revealed a combination of mutation PIK3CA p.E542K and HLA A*11:01, which was detected in 0.54% of all patients. Additionally, 43.6% (106/243) of patients were diagnosed with nasopharyngeal carcinoma, among whom 42% (44/106) possessed predicted neoantigens, including 15 patients with strong-binder neoantigens. Conclusions: (1) Neoantigen-based vaccination is a practical measure to treat patients with head and neck cancer, as indicated by the percentage of patients harboring strong-binder neoantigens. (2) Off-the-shelf neoantigen vaccines may not be practical, given the result that the most common combination of a neoantigen-producing mutation and the corresponding HLA was only found in 0.54% of all patients.
Are the demographics of recurrent oropharyngeal and oral cavity squamous cell carcinoma changing?
Authors: Means Jeffrey , Stram Douglas , Katzel Jed Abraham
Published: May 2020

e18537

Background: In the current era of human papillomavirus (HPV)-related oropharyngeal cancer and decreasing alcohol and tobacco use, the demographic factors associated with recurrent head and neck cancer may be evolving. We evaluated clinical and demographic factors in a cohort of patients with recurrent and non-recurrent Oral Cavity (OC) and Oropharyngeal Squamous Cell Carcinoma (OPSCC) in order to evaluate which factors are associated with tumor recurrence and how these factors are modified by HPV status. Methods: From a cohort of 3201 patients diagnosed with OC and OPSCC at Kaiser Permanente Northern California between 1/1/2008 and 6/30/2019, 235 recurrent cases were identified. Clinical and demographic factors were extracted from electronic medical records. We calculated frequencies of demographic and clinical factors stratified by recurrence and HPV status, and reported p-values using the chi-square test for independence. Results: HPV-related cases were more likely to be male (84% vs. 64%), younger (80% ≤70 years old vs. 55%), have fewer comorbidities (61% with non-cancer Charlson index < 1 vs. 47%), and higher cancer stage (88% with a stage > 1 vs. 42%) than HPV-unrelated cases. Recurrent HPV-unrelated cases were more likely to be Asian (14% vs. 8%), and from higher income census tracts (75% from tracts with median household income > $60,000 vs. 66%) than recurrent HPV-related cases. Chi-square p-values of < 0.001. Recurrence and HPV status did not appear to be associated with prior smoking and alcohol abuse. Conclusions: Our cohort verifies that HPV-related OPSCC patients are more likely to be younger, male, and with lower Charlson scores, while recurrent HPV-unrelated OC and OPSCC may be more common among Asians and individuals from higher-income census tracts. This may have important implications for future clinical trial design and surveillance for recurrence. [Table: see text]
Prediction of local recurrence in oral squamous cell carcinoma using immune markers.
Authors: Pierssens Damiana , Mulder Frans , Van Den Hout Mari , Sluijpers Niels , Kessler Peter , Kremer Bernd , Speel Ernst-Jan M.
Published: May 2020

e18538

Background: The local recurrence rate of oral squamous cell carcinomas (OSCC) hardly decreases despite the best possible treatment. Partly, this is caused by the presence of (pre)malignant cells in the surrounding tissue, which can develop into a new malignancy in time. Histological recognition of these cells in resection margins appears to be difficult during routine practice. The aim of this study was to determine whether or not the presence of immune cells in OSCC resection margins may predict the development of a recurrence in these patients. Methods: Thirty-four patients with firstly diagnosed, radically resected primary OSCC with histopathological confirmed tumor-free margins (treated between 1993 and 2003) were included. Nine patients out of the 34 patient developed a locoregional recurrence within 5 years. Formalin-fixed paraffin-embedded tissue sections of 34 resection margins were subjected to immunohistochemistry for CD45, CD3, CD4, CD8, PD-L1 and PD-1 expression in immune cells, after which a quantitative analysis of the largerst distribution of CD45-, CD3-, CD4-, CD8-, PD-L1 and PD-1 positive lymphocytes on each resection margin has been photographed. The highly immunostained surface in relation to the total surface has been measured up to 100μm below the squamous epithelium. This analysis has been performed using QWin software (Leica). All data were analyzed using GraphPad Prism (version 7.05 for Windows, GraphPad Software, La Jolla California USA, www.graphpad.com). Results: Only CD3 and CD8 had a moderate correlation (Spearman = 0.68). A high expression of CD45 (≥7.7% ) and CD4 (≥5,4%) was strongly correlated with a worse disease-free survival (p = 0.0054 and p < 0.001, respectively), as was a low CD3 expression (≤5,9%) (p = 0.0211). PD-L1 and PD-1 expression analysis did not show a significant association with recurrence risk. Conclusions: A high amount of CD45-, and CD4- and a low amount of CD3-positive immune cells in OSCC resection margins may predict local recurrence.
Prevalence of herpes simplex virus I, II, cytomegalovirus, Epstein–Barr virus and human papillomavirus (6, 11, 16 and 18) in normal oral mucosa and OSCC patients in Saint-Petersburg (Russia).
Authors: Kutukova Svetlana , Beliak Natalia P. , Ivaskova Julia V. , Chuhlovin Alexey B. , Yaremenko Andrey I. , Ermakova Tatiana S.
Published: May 2020

e18539

Background: The objective of our study was to evaluate the prevalence of DNA of HSV I, II, CMV, EBV, HPV6.11, HPV16, HPV18 in normal oral mucosa and oral squamous cell carcinoma (OSCC), and determine this association with long-term treatment outcomes and patient survival. Methods: The study included 116 patients with OSCC (stage I-IVB who received standard treatment) and 50 healthy volunteers, median age 60.0 yrs (95% CI 58.0-64.0). Using real-time PCR (polymerase chain reaction), freshlyfrozen samples of the tumor and normal mucous membranes of the cavity were analyzed. mouths, which, after collection, were placed in an EDTA solution and frozen at 20°C. Results: In 54 (46.55%) OSCC and 17 (34.00%) normal mucous viral DNA was not found (p = 0.13). The occurrence of DNA (OSCC vs. normal) of the following viruses was the same in both OSCC and normal mucosa: HSV I, II: 2 (1.72%) vs. 2 (4.00%) (p = 0.38); EBV: 40 (34.48%) vs. 15 (30.00%) (p = 0.57); CMV: 5 (4.31%) vs. 2 (4.00%) (p = 0.93); HPV6.11: 16 (13.79%) vs. 6 (15.00%) (p = 0.84); HPV16: 12 (10.34%) vs. 2 (4.00%) (p = 0.18). HPV18 DNA: 20 (17.24%) vs. 24 (48.0%) (p <0.0001) was found significantly less frequently in the OSCC group. In addition, EBV + HPV18: 7 (14.00%) vs. 5 (4.31%) (p = 0.0270) was more common vs. OSCC in the group of healthy volunteers; CMV + HPV18: 2 (4.00%) vs. 0 (p = 0.0302). In the OSCC group, patients with stage III disease were more often virus-positive (p = 0.0137); the pterygo-maxillary fold region (p = 0.0438); with partial keratinization of cells (p = 0.05). PFS in the HPV18 (+) OSCC group was 38.5 months (95% CI 11.00-66.0) and 23.5 m higher than the group of HPV18 (-) patients (HR = 0.63; 95% CI 0.39-1.03; p = 0.0399). In virus-negative patients, PD was more often recorded: 12 (24.00%) vs. 2 (3.03%) (p = 0.0006). In the group of virus-positive patients, OS and PFS, even with non-radical treatment, were significantly higher than virus-negative patients with radical treatment. OS: vir (+)/non-radical = 69.0 mo vs. vir (-)/radical = 15.0 mo (HR = 0.22; 95% CI 0.11-0.47; p <0.0001). PFS: vir (+)/non-radical = 56.0 mo vs. vir (-)/radical = 11.0 mo (HR = 0.20; 95% CI 0.09-0.45; p <0.0001). Conclusions: The association of OSCC with viral DNA, especially HPV18, is a favorable prognosis of the disease and a longer OS and PFS, even when radical treatment is not possible.
PD-L1 in combination with CD8+TIL and HIF-1α are promising prognosis predictors of head and neck squamous cell carcinoma.
Authors: Yu Jinming , Zhou Zihan , Mu Dianbin , Zhang Dexian , Zhang Xianbin , Ding Xingchen , Yang Jia , Bai Xinbin , Yu Jinming
Published: May 2020

e18545

Background: Currently, the tumor/node/metastasis (TNM) staging is the most widely used Head and neck squamous cell carcinoma (HNSCC) staging system. However, this classification only provides limit information for the prognosis of HNSCC. Recently, some studies suggest that the level of PD-L1 in tumor cells (TC-PD-L1) or in tumor microenvironment cells (TMC-PD-L1) is a promising biomarker for the prognosis of HNSCC patients. Therefore, in this study, we evaluated the prognostic value of TC-PD-L1, TMC-PD-L1, CD8+ TIL, HIF-1α. In addition, we investigated if incorporated these biomarkers into TNM stage could improve the prognostic value of TNM stage. Methods: A total of 63 patients who underwent surgical resection. The level of PD-L1, CD8+ TIL and HIF-1α was determined by immunohistochemical analysis. The survival of patients was evaluated by Kaplan-Meier analysis and Cox proportional hazards model. The prognostic power of these parameters was evaluated by C-index. Results: We observed that the survival of patients, who had high level of PD-L1 in tumor cells, was significantly shorter than those who had low level of PD-L1. However, the survival of patients who had high level of PD-L1 in tumor microenvironment was significantly longer than patients with low level of PD-L1 in tumor microenvironment. In addition, high level of CD8+ tumor-infiltrating lymphocyte or low level of HIF-1α level suggests a better prognosis. Moreover, we observed that PD-L1 in combination with CD8+tumor-infiltrating lymphocyte and HIF-1α could significantly improve the prognostic effect of current TNM stage. Conclusions: The results of this study suggest that the level of PD-L1, CD8+TIL and HIF-1α is useful prognostic biomarkers for patients with HNSCC. Incorporated these biomarkers into current TNM stage of HNSCC improve the discriminatory capability of TNM stage.
Efficacy and safety of neoadjuvant chemotherapy (NACT) with paclitaxel plus carboplatin and oral metronomic chemotherapy (OMCT) in patients with technically unresectable oral cavity squamous cell carcinoma (SCC).
Authors: Kashyap Lakhan , Patil Vijay Maruti , Dhumal Sachin Babanrao , Noronha Vanita , Joshi Amit , Menon Nandini Sharrel , Prabhash Kumar
Published: May 2020

e18550

Background: NACT regimen for patients with oral cavity scc is based on maximum tolerated doses (MTD). Combination of MTD and metronomic chemotherapy schedule will lead to initial debulking of tumor and subsequent inhibition of angiogenesis, this may produce synergistic effect and overcome the drug resistance of MTD schedule. We assessed the efficacy and safety of this combination as NACT in patients with technically unresectable oral cavity SCC. Methods: This is retrospective analysis of prospectively maintained data. Fourteen patients having technically unresectable oral cavity SCC received NACT with paclitaxel (175mg/m2) plus carboplatin (AUC5) 3 weekly (MTD schedule) and OMCT (methotrexate 9mg/m2 once a week, celecoxib 200mg twice daily and erlotinib 150mg once daily). Patient were assessed clinically and radiologically after minimum of two cycles for resectability. Radiological response was evaluated as per RECIST 1.1. We report response rate, resectability and tolerance of this NACT regimen. Results: Median age of the patients was 38 years. Twelve patients (85%) were male. Twelve (85%) and two (15%) patients had buccal mucosa and oral tongue primary respectively. AJCC 2017 stage IVA and IVB disease was present in 85% and 15% patients respectively. Reason for technical unresectabilty was skin edema above zygoma in five (36%), high infratemporal fossa involvement in five (36%), nodal encasement of major vessels in two (14%) and posterior extent of oral tongue tumor into oropharynx in two (14%) patients. Median number of NACT administered were three. The tumor of nine (64%) patients showed partial response and none of the patients had tumor progression. Tumor of nine patients (64%) were deemed resectable after NACT. Common grade 3/4 toxicities (CTCAE 5.0) were neutropenia in eight (57%), thrombocytopenia in three (21%), febrile neutropenia, hypokalemia and diarrhoea in two patients (14%) each. Conclusions: Paclitaxel and carboplatin along with OMCT is well tolerated and easily administered NACT regimen with high response rate and resectabilty in patients with technically unresectable oral cavity SCC.
Effect of leucovorin on radiation-induced brain injury and tumor radiosensitivity in patients of NPC: A retrospective analysis.
Authors: Liang ZiBin , Wang Siyang , Yang Shuai , Long Feiyu , Jiang Lifeng , Zou Yanfei , Pan Jinmei , Lin Zhong , Cheng Zhibin
Published: May 2020

e18552

Background: Nasopharyngeal carcinoma (NPC) is a typical type of head and neck cancers with its high prevalence areas in Southeast of China. On account of the prolongation of life, the severe complications developed such as radiation encephalopathy (REP). Currently many methods are used to cure REP but the outcomes are limited, such as corticosteroids, hyperbaric oxygen, antiplatelet agents and so on. The aim of this study is 1) to evaluate the protective effect of Calcium leucovorin (LV), a reduced folic acid, on REP in NPC patients. 2) to investigate the progression-free survival (PFS) and overall survival (OS) in NPC treated with or without LV. Methods: We conducted a retrospective, observational cohort study using de-identified, curated data in the Fifth Affiliated Hospital of SYSU included 1075 patients diagnosed as NPC of Stage II, III, or IVa who had been treated from December 2002, through February 2014. The Leucovorin-Group (LV-Group) of 163 NPC patients were matching the preceding criteria and agreed to receive PFL chemotherapy (cisplatin 80 mg/m², 5-fluorouracil 1000 mg/m²/d, and leucovorin 120 mg/m²) every 3 weeks. The Non-leucovorin-Group (NLV-Group) of 913 patients with similar disease status who did not receive leucovorin during the same period. Histologically there were 260 patients of PF chemotherapy (PF-Group) and 653 patients of other regimen chemotherapy (NPF-Group) in NLV-Group. REP were evaluated according to MRI and CT scan imaging studies. Time to progress (TTP), the real-world local control rate (rwLCR) and OS were compared across the two cohorts using the log-rank test. REP were compared using Chi-Square and Fisher’s Exact Test. Results: The TTP of the LV-Group as compared to the NLV-Group at 3, 5, 8, 10,12 and 16 years were 98.96% vs 94.97%, 95.57% vs 90.08%, 92.01% vs 85.22%, 90.67% vs 84.39%, 88.59% vs 84.26% and 88.54% vs 81.06%, respectively. The incident of REP in LV-Group is lower than that of the NLV-Group significantly( P= 0.0413). The OS of LV-Group as compared to PF-Group at 3, 5,10 and 12 years were 97.42% vs. 91.24%, 94.61% vs. 87.44%, 88.74% vs. 81.98%和88.74% vs. 78.57%, respectively. The OS of LV-Group got higher than that of PF-Group ( P= 0.0269). The OS of LV-Group was significantly higher than that of PF-Group with 90.83% vs. 82.12% in stage I-III(P = 0.0348). The rwLCR of LV-Group as compared to PF Group were 97.06% vs. 73.91% in stage T4 ( P= 0.0133). Conclusions: Leucovorin can significantly reduce the incidence of REP of NPC combined with PF regiment. It may improve the tumor radiosensitivity in NPC patients.
Carboplatin versus cetuximab chemoradiation in cisplatin ineligible locally advanced head and neck squamous cell carcinoma.
Authors: Thanikachalam Kannan , Krishnan Jayasree , Siddiqui Farzan , Ali Haythem Y. , Sheqwara Jawad
Published: May 2020

e18555

Background: Squamous cell carcinomas (SCC) of Head and neck are associated with tobacco, alcohol use and HPV infection. About 60% of patients with head and neck cancers(HNC) are locally advanced on diagnosis. Concurrent chemoradiation (CCRT) is standard of care in inoperable locally advanced HNC(LA-HNC), high risk adjuvant setting and organ function preservation. While cisplatin (CDDP) is the standard of care for CCRT, alternatives are carboplatin alone or cetuximab alone or carboplatin in combination with 5-FU or paclitaxel CCRT in CDDP ineligible setting. Methods: Patients with LA-HNC (SCC), from 01/01/2013-12/31/2018, who were ineligibile for CDDP CCRT and who received either carboplatin or cetuximab CCRT were included. Patients who received induction chemotherapy and had nasopharynx primary were excluded. 68 patients were analyzed to evaluate outcomes in patients who received carboplatin CCRT and cetuximab CCRT. Progression free survival (PFS) and Overall survival (OS) were calculated by Kaplan Meier analysis with SPSS v26. Results: There was a trend toward improved PFS in CarboRT group among oropharynx HNC patients who were P16 Negative(-ve) (59.5 months(m) vs 37.7 m, p value – 0.069). Among oropharynx HNC patients who were p16 positive, there was no statistically significant difference in PFS among CarboRT vs CetuximabRT (45.8 m vs. 39.77 m, p value – 0.51). OS was favorable towards carboRT in oropharynx SCC p16-ve group (59.5 m vs. 40.97 m, p value – 0.41). There was no difference in OS in p16+ve Oropharynx SCC group, who received CarboRT and CetuximabRT (45.74 vs. 45.94 m, p value – 0.77). When patients were analyzed regardless of their p16 status, site or stage, patients who received CarboRT had a higher OS at 56.30 m (95% CI 45.10-67.50%) vs. 38.11 m (95% CI 28.84-47.38%) among patients who received CetuximabRT (p value-0.048). Though PFS clinically favored carboRT group, when compared to CetuximabRT (55.43 m vs. 36.75 m), it was not statistically significant (p value – 0.10). Conclusions: In our analysis, patients who received single agent carboplatin CCRT had higher OS when compared to cetuximab CCRT. Though other outcomes favored carboplatinRT including PFS among entire group and p16-ve group, OS in p16-ve patients, it was not statistically significant, which is likely due to low power. Based on our analysis, for LA-HNC, carboplatin CCRT should be favored over cetuximab CCRT for patients ineligible for CDDP, particularly in P-16 -ve disease. Further randomized clinical trials can shed more data in this reduced intensity regimen.
Lymphnode metastasis patterns in primary sites of hypopharyngeal cancer: A retrospective analysis from multicenter data.
Authors: Zhang Xiwei , An Changming , Sun Ying
Published: May 2020

e18559

Background: Understanding the pattern of lymph node metastasis (LNM) in hypopharyngeal cancers (HPC) could help both surgeons and radiologists make decisions in the management of cervical lymph node. Our objective is to identify the pattern of nodal spread and the relationship between features of primary tumor and LNM in HPC. Methods: 244 newly diagnosed HPC patients during 2014 to 2017 were recruited from 3 specialized cancer hospitals in mainland China. All patients underwent head and neck magnetic resonance imaging(MRI) and received definitive radiotherapy ± concurrent chemotherapy. The features of primary tumor (tumor size, primary location, and extent of invasion) and the involvement of lymph nodes in each level were reassessed. According to the incidence of LNM, these levels were sequenced and sorted into drainage stations. Meanwhile, univariate and multivariate analysis was used to determine the risk factors for bilateral and regional lymph node metastasis. Results: The cohort consisted 195 piriform sinus cancers (PSC), 47 posterior wall cancers (PWC), 2 Post-cricoid cancers (PCC). 176 patients (72.1%) presented with MRI-detectable LNM. The overall LNM rates for level II-VI and retropharyngeal lymph nodes (RPLNs) were 59.0%, 52.9%, 14.3%, 1.6%, 2.9% and 14.7% respectively. Based on the prevalence of LNM in each level, we suppose that the lymphatic drainage of PSC was carried out in sequence along three stations: Level II & III (61.0% & 55.4%), Level IV & RPLN (15.9% & 10.3%), and Level V & VI(1.5% & 3.1%). While, for PWC the lymphatic drainage is carried out along two stations: Level II, III & RPLN (48.9%,40.4% & 34.0%), and Level IV-VI (6.4%, 0% and 2.1%). According to univariate analysis, primary subsite, posterior wall, post-cricoid and non-pyriform sinus invasion were correlated with bilateral LNM. The presence of RPLNs was correlated with larger tumor size(>4cm), primary subsite, posterior wall and non-pyriform sinus invasion. In further multivariate analysis, posterior wall invasion was significantly correlated with bilateral LNM (P = 0.030, HR = 2.853 95%CI, 1.110-7.338). Tumor size > 4cm(P = 0.017, HR = 2.545, 95%CI,1.180-5.488) and posterior wall invasion(P = 0.017, HR = 2.880 95%CI, 1.209-6.862) were correlated with RPLN metastasis. Conclusions: Different primary sites of HPC have different lymphnode metastasis patterns. Piriform sinus cancer tends to metastasize to the ipsilateral Level II&III. Posterior wall cancer tends to metastasize bilaterally to Level II, III and RPLN.
The role of routine surveillance imaging in detecting oral cavity cancer recurrence in asymptomatic patients.
Authors: Chi Jeffrey , Chung Su Yun , Lopez Carlos Alberto , Frank Douglas K. , Pereira Lucio , Gabalski Edward Z. , Teckie Sewit , Ghaly Maged , Seetharamu Nagashree
Published: May 2020

e18561

Background: The optimal surveillance approach for patients who were definitively treated for oral squamous cell carcinoma (OSCC) is unclear, but it includes physical exams (PE) and surveillance imaging (SI) studies at intervals that vary amongst institutions. At our institution, patients are seen in office and underwent PE monthly for the first 3-6 months then every 3 months thereafter. SI is performed every 3 months during the first 2 years, every 6 months till year 4, and yearly thereafter. Concerning symptoms or findings resulting from PE or SI may trigger further tests including biopsies as deemed necessary by treating team. In this study, we investigated value of SI in detecting recurrence of OSCC. Methods: Retrospective chart review was performed for the patients who were diagnosed with OSCC from 2014 to 2017 at our institution. Eligible patients included those who underwent definitive treatment (surgery, chemotherapy, radiation) of OSCC with curative intent. Patients without evidence of disease on post treatment imaging were included. Results: Two hundred OSCC patients were treated definitively. 138 (69%) patients had local disease and 62 (31%) patients had regional disease. 183 patients (%) had no clinical evidence of disease on post treatment baseline imaging. Patients who had residual disease on post-to scab were excluded from further analysis. The median follow-up was 29 months. 2-year overall survival was 87.4%. 82 patients underwent biopsy for suspicious findings and 44 patients had confirmed recurrence. 37 (84.1%) of the recurrences occurred in the first two years. 28 (63.6%) of recurrences were local, 13 (29.5%) were regional and 3 (6.8%) were metastases. 31 (70.6%) of patients with disease recurrence presented with clinical symptoms or had suspicious findings on PE. 13 (29.4%) of the recurrences were detected by SI alone (PPV=54.2 %) in asymptomatic patients most of which (92.3%) occurred within first 2 years. Conclusions: Majority of OSCC recurrence were detected due to clinical symptoms or positive findings on PE. However, 29.4% of recurrences were detected by SI alone in asymptomatic patients suggesting a role for SI for the first 2 years post-treatment of OSCC. Larger prospective studies are needed to determine the optimal frequency of SI.
Comparative efficacy of primary treatment approaches in anaplastic thyroid carcinoma (ATC): An updated network meta-analysis.
Authors: Gallagher Kevin M. , Haddad Philip A. , Hammoud Dalia A.
Published: May 2020

e18566

Background: ATC is a rare tumor accounting for around 5% of all thyroid cancers. With survival measured in months, ATC is often fatal despite combined therapeutic approaches. Several studies reported on ATC treatment modalities indicating different outcomes and occasionally conflicting results. This analysis was conducted to update and expand our existing knowledge of the relative efficacy of the available therapeutic modalities in this rare disease. Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of (i) English language, (ii) diagnosis of ATC, (iii) treatment with complete resection (SX), radiotherapy (RT), surgery and radiotherapy (SRT), chemoradiotherapy (CRT), and combined surgery, radiation, and chemotherapy (COMB), and (iv) comparative studies reporting survival rates. A frequentists network meta-analysis was conducted using netmeta package and random-effects model. Results: Six studies comprising a total of 476 participants were included. SX, RT, CRT, SRT, and COMB approaches demonstrated significant survival advantage over no treatment and/or palliative care. Using odds ratio for analysis, COMB ranked highest followed by SRT, SX, CRT, and RT in a decreasing order. Inconsistency analysis did not reveal any significant differences between direct and indirect estimates. Conclusions: This network meta-analysis is the first to compare and rank commonly used treatment modalities in ATC. It indicates that SX and RT remain the backbone for any treatment approach that significantly impacts survival in ATC.
A phase II randomized clinical trial and mechanistic studies using improved probiotics to prevent oral mucositis induced by concurrent radiotherapy and chemotherapy in nasopharyngeal carcinoma.
Authors: Jiang Chunling
Published: May 2020

e18568

Background: Earlier evidence has proven that probiotic supplements can reduce radiochemotherapy (CCRT) -induced oral mucositis (OM) in nasopharyngeal cancer (NPC). We have recently modified the ingredient of the probiotics by combining Bifidobacterium animalis, Lactobacillus plantarum, Lactobacillus rhamnosus and Lactobacillus acidophilus. This report includes the Phase II clinical trial to evaluate the effect of the modified probiotics along with mechanistic studies. Methods: We enrolled 85 patients with locally advanced NPC who were undergoing CCRT. The patients were randomized (1:1) to receive either probiotic mixture or placebo. The incidence of severe OM (grade 3 or higher) was the primary endpoint to document. We utilized a rat model. We collected rat’s samples from the tongue, blood and fecal and proximal colon tissues on a various days following treatment and tested for the mechanism of probiotics mixture on OM. Results: We found that patients taking the probiotic mixture showed significantly reduced OM. The incidences for Grade 0, 1, 2, 3 and 4 OM in the placebo group and the probiotic mixture group were 0%, 14.7%, 38.2%, 32.4%, and 14.7% and 13.9%, 36.1%, 25%, 22.2%, and 2.8%, respectively. Furthermore, patients in the probiotic mixture group showed lower reduction rate in CD3+ T cells (75.5% vs 81%, P < 0.01), CD4+ T cells (64.53% vs 79.53%, P < 0.01), and CD8+ T cells (75.59% vs 62.36%, P < 0.01) compared with the placebo group. In the rat model, the control group rats showed more severe mucositis, increased histologic changes of the oral mucosa on the 7th, 14th and 21th day, with the 14th day most significant. CCRT also caused an enhanced inflammation response and cell apoptosis in tongue in the control group. Moreover, CCRT increased the intestinal permeability through reducing the zonula occludens-1(ZO-1) and Claudin-1 expression in colon tissues and increasing the inflammation factors in bloods. The structure of gut microbiota was also disturbed in the control group mainly with the increasing abundance of Bacteroidetes and decreasing abundance of Firmicutes. However, probiotics mixture ameliorated the severity of OM, decreased the inflammation response, cell apoptosis, intestinal permeability, and restored the structure of gut microbiota to normal. Conclusions: The modified probiotic mixture significantly reduces the severity of OM through enhancing the immune response of patients and modifying structure of gut microbiota. Clinical trial information: NCT03112837.
BRAF V600E-mutated anaplastic thyroid carcinoma (ATC) and treatment with BRAF-inhibitors: Real-world data from a single-institution, still far from the cure.
Authors: Platini Francesca , Ortolan Elisa , Cavalieri Stefano , Massa Giacomo , Filippini Daria Maria , Alfieri Salvatore , Bergamini Cristiana , Resteghini Carlo , Orlandi Ester , Paolini Biagio , Piazza Cesare , Perrone Federica , Tamborini Elena , Ferrarini Linda , Serafini Mara Serena , Cappelletti Vera , Daidone Maria Grazia , Licitra Lisa F. , Locati Laura Deborah
Published: May 2020

e18577

Background: ATC is a very aggressive disease. In the last years new insights on molecular profile of ATC have led to novel therapeutic options, primarily BRAF-targeted agents. Methods: From May 2018 to December 2019, data on recurrent/metastatic ATC patients treated at our Institution have been reviewed. BRAF V600E was assessed in each patient. BRAF mutation was tested both on tumor sections and on cell-free DNA (cfDNA). Circulating BRAF V600E was assessed by using Droplet Digital PCR (ddPCR) Technology. BRAF wild-type (WT) patients were treated with standard chemotherapy (adriamicin or taxans or platinum-based regimens). BRAF V600E patients were treated with dabrafenib 300 mg per day and trametinib 2 mg per day (combo regimen) until progression or unacceptable toxicities. Response was assessed by RECIST 1.1; progression-free survival (PFS) and overall survival (OS) were estimated with Kaplan-Meier method and compared with log-rank test. Safety was evaluated according to CTCAE version 5.0. Results: 16 ATC patients were included. Male/female 5/11, median age was 68 years (range 43-80). Eight patients (50%) carried BRAF mutation. Best response in BRAF V600E was 4 partial response (PR), 3 stable disease (SD) and response in 1 patient has not been assessed yet. Combo was well tolerated, the most common adverse events (G2) were fatigue (14%), pyrexia (14%), nausea and vomiting (9%). Only one patient experienced drugs interruptions. Best response in BRAF WT patients was SD for 1, progressive disease for 4 and 3 patients received supportive care. Concordance between circulating BRAF status with tumor tissue was 80%. Assessment of circulating BRAF performed at baseline and at best response was available for 3 patients achieving a PR: mean reduction was -99.48% from baseline (range -99.37 – -99.66%). Median follow up was 22.8 weeks (95% CI 12.8-22.8). Median PFS was 13 weeks in BRAF V600E and 7.4 weeks in BRAF wt patients (p=0.1); in the same groups median OS was 18.4 and 7.8 weeks, respectively (p=0.051). Conclusions: Real-life data with combo regimen showed an ORR of 50%, with short PFS and OS. Reduction of circulating BRAF observed during treatment might be an indirect marker of tumor shrinkage, even if more data are needed to correlate circulating BRAF and disease response.
Pediatric cancer care in Armenia: The results of a qualitative analysis.
Authors: Hovhannisyan Saten , Papyan Ruzanna , Sargsyan Lilit , Danielyan Samvel , Vagharshakyan Lala , Avagyan Anna Artak , Hoveyan Julieta , Tamamyan Gevorg
Published: May 2020

e19002

Background: In Armenia the incidence of pediatric cancer accounts for around 80-100 cases per year. This qualitative study was conducted in 2018 to evaluate the needs and challenges in a provision of pediatric cancer care in Armenia. Comparative qualitative study was conducted in 2020 to evaluate the progress in the field. Methods: Qualitative research methods were incorporated to evaluate the achievements, needs and challenges in a provision of childhood cancer care in Armenia. Semi-structured in-depth interviews were conducted with selected study participants including pediatric oncologist/hematologists, pediatric surgeons, who also treat cancer patients, and radiation oncologists. Purposive sampling technique and qualitative conventional content analysis methods were used. Results: Data collected in January 2020 has shown significant improvements in the field of pediatric oncology in Armenia. In the 2018 study, some of the major issues included lack of centralized pediatric cancer care, pediatric cancer registry, palliative care center, possibility of providing high-dose methotrexate, limited nursing training, multidisciplinary team approaches and use of central catheters. Within two years, majority of these problems were solved or are in the process. In 2019 all 3 pediatric oncology and hematology units were merged and the Pediatric Cancer and Blood Disorders of Armenia was created; with the support from charitable foundations all children with cancer receive free medical and psychosocial coverage; a 25 year data has been collected from all the possible sites, the first pediatric cancer palliative care is under construction, 4 multidisciplinary cancer teams were created, pediatric oncology and hematology fellowship was created at the Yerevan State Medical University to prepare for the first time "pediatric oncologist-hematologist" as a one profession. The existing major problems include very limited provision of pediatric cancer medications by the government, as well as lack of the official registration of the number of essential drugs included in the WHO list. Conclusions: Twinning programs, multidisciplinary team discussions with international experts, improvement in availability of several resources, professional development of the staff are major tools for the progress of pediatric oncology in Armenia. Poor provision and official registration of anti-neoplastic medications by the government still remain a major obstacle.
Disparities in clinical characteristics and treatment of multiple myeloma in African American patients.
Authors: Mathura Shivam , Lane Daniel , Hansen Eric , Belli Andrew J. , Venkatesan Priya , Wang Ching-Kun , Fung Vicki Kay , Geng Xiaoqi , Norden Andrew D.
Published: May 2020

e19008

Background: Based upon interesting recent published findings, we characterize disparities in clinical characteristics, treatment patterns, and outcomes for African American (AA) patients with multiple myeloma (MM) using real-world (RW) data. Methods: A random sample of patients diagnosed with MM were selected from the COTA RW database for the retrospective analysis to be stratified by race, AA (n=395) and other (n=396). To adjust for differences in age and gender, case-control matching was performed. Patient characteristics and treatment patterns were summarized. A Cox proportional hazards model was used to evaluate the relationship between patient characteristics and time to stem cell transplant (SCT). Overall Survival (OS) was calculated using the Kaplan-Meier method. Results: Median time from diagnosis of active MM to start of first-line (1L) treatment was longer among AA as compared to the other cohort (23 vs. 17 days respectively, p=0.01); VRD was the most common 1L therapy (17.39% vs. 18.58% respectively). The percent of patients receiving SCT was similar across racial cohorts (64.56% vs. 66.16%), but AA patients had a longer time to first SCT (234 vs. 204.50 days, p=0.01). Among all patients, Charlson Comorbidity index (CCI) score of 0 (HR: 2.85, CI: 1.77-4.58) and CCI score of 1-2 (HR: 2.79, CI: 1.73-4.49) were significantly associated with an increased likelihood of receiving a SCT. MM diagnosis at an older age was associated with a lower likelihood of receiving a SCT (HR: 0.97, CI: 0.96-0.98). AA cohort exhibited a higher incidence of prior history of MGUS (10.63% vs 8.08%). Cytogenetic profile of the AA and other cohorts are shown in the Table below. Median OS was similar between the AA and other cohorts (145.61 vs. 146.50 months, respectively, p=0.88). Conclusions: AA patients had a longer duration of time to 1L therapy and 1st SCT in our RW study. Despite these differences in time to treatment, OS was similar across racial groups. Future studies are needed to explore the significance of our RW findings and other potentially important clinical characteristics. [Table: see text]
Barriers identified in a patient navigation program for starting and completing definitive radiotherapy treatment in a limited resource setting.
Authors: Vieira Carolina Martins , Krush Lindsay , Goss Paul E. , Rodrigues Angelica Nogueira
Published: May 2020

e19018

Background: In addition to limited radiotherapy (RT) resources, there is enormous complexity involved in the registration process for attending RT services in Brazil. The process involves so many steps that, in combination with the lack of information and guidance, makes the patients often get lost within the system. Hospital das Clínicas da UFMG (HC UFMG) is a teaching hospital that belongs to the 3rd largest university in Brazil and, despite its important cancer center, it does not have its own radiotherapy center. That makes the RT process even more complex, since the patient ends up receiving chemotherapy in one center and RT in another, a common scenario in low- and middle-income countries (LMICs).Thus, it is necessary to optimize the scarce resources available, taking also into account the social difficulties involved. Patient barriers to accessing care were evaluated throughout a patient navigation (PN) study in Brazil, in order to better help the navigator identify areas of possible intervention. Methods: In a pilot study (non-randomized) carried out in partnership with the Global Cancer Institute, patients with cancer of the cervix, rectum, esophagus, anal canal, head and neck, lung, and prostate who were considered candidates for neoadjuvant or definitive RT were evaluated and questionnaires were applied to identify obstacles for RT, in order to guide a PN program and help to orient health policies. Results: Seventy-three patients were interviewed (1 excluded). The majority had locally advanced disease, the most prevalent sites being esophagus, head and neck and rectum. The most common barriers are shown in the table. 100% of the patients reported at least one obstacle, 93% between 2 and 7 obstacles and 1 patient quoted 13 of them. Conclusions: Proper identification of barriers involved in treatment, especially in a low resource setting is mandatory in order to guide PN program`s goals and establish public health demands. Many barriers identified may be overcome with PN programs in LMICs. [Table: see text]
Change in body mass index in breast cancer patients in the first two years from diagnosis.
Authors: Abu-Khalaf Maysa M. , Shimada Ayako , Nikita Nikita , Micaily Ida , Hackbart Hannah , Lu-Yao Grace L. , Butryn Meaghan
Published: May 2020

e19020

Background: The rate of obesity in adults is 34% in the city of Philadelphia, with rates being highest among non-Hispanic blacks and Hispanics. We sought to evaluate how BMI varies by age and race/ethnicity at time of initial encounter for a breast cancer (BC) diagnosis (dx), and investigate factors predictive of BMI change in the first 2 years of dx. Methods: We identified 1,833 patients (pts) in our electronic medical record, (1/2015-present), who had a BC dx at their first hospital or ambulatory encounter using ICD-10 code C50.X, and had BMI recorded at baseline (BL) (6 mo pre-and up to 3 mo post), at 1 yr +/- 3 mo and 2 yr +/- 6 mo. We summarized demographic data (age, gender, marital status, race/ethnicity) with mean and standard deviation for continuous variables and with count and percentage for categorical variables. Descriptive statistics were summarized by 3-level BMI categories: underweight/normal (≤ 24.9), overweight (25 to 29.9), and obese (>30) and compared with ANOVA test, Chi-square-test or Fisher’s exact test as appropriate. Mixed effect regression analysis was conducted to adjust for the effects of time (i.e., BL, 1 yr, 2 yr), gender, race/ethnicity and the interaction of time and race and ethnicity in estimating mean BMI. We calculated the mean change of BMI between the BL and later time points by race/ethnicity. The significance level of all tests was set a priori to the 0.05 level. Results: 99.4% of pts were female; mean age was 63 yrs; White (60 %), Black/AA (27 %). By BMI category, we did not observe a substantial difference in the mean age of dx and gender (p = 0.18 for age and p = 0.55 for gender). We observed a substantial difference in race/ethnicity among BMI categories (p < .0001); the highest percentage of obese pts were Black/AA. In the mixed effect model, the reference level was set as a white female with an average (avg) systolic blood pressure of 137.8. The estimated avg BL BMI of this reference group was 28.8. We observed that among Asian/Pacific Islander (API) pts the avg BL BMI is lower by 3.5 ( p < .0001) and among female Black/AA pts the avg BL BMI is higher by 2.6 ( p < .0001) compared to reference group. No significant change was noted in mean BMI between BL and 1 yr for any race and ethnicity group, and only the Hispanic/Latino group had a declining trend for change in BMI between BL and 2 yr (estimate: -1.9; 95% CI: -5.9, 2.1). Conclusions: In our cohort, Black/AA pts likely have higher BL BMI and API pts likely have lower BL BMI compared to White pts. We found no significant difference in change of BMI by race and ethnicity group during the first 2 years from an initial encounter for a BC dx.
Exclusion rates of patients living with HIV from cancer immunotherapy clinical trials.
Authors: Vora Kruti Bhagirath , Awad Mark M.
Published: May 2020

e19035

Background: Although patients living with HIV are at increased risk for developing several cancers, they have often been excluded from practice-changing immunotherapy clinical trials across many tumor types. Emerging retrospective and prospective studies indicate that immunotherapies can be safe and effective in patients with HIV. ASCO and Friends of Cancer Research have supported the inclusion of patients with HIV in cancer clinical trials. We determined the rate of HIV exclusion from recent cancer immunotherapy clinical trials according to tumor type, immunotherapy treatment, and phase of trial. Methods: We compiled trials on the ClinicalTrials.gov database with study start dates from January 1, 2019 to October 10, 2020, using the search term “cancer” for disease, and the following intervention terms: “immunotherapy, PD-1, PD-L1, CTLA-4, pembrolizumab, nivolumab, atezolizumab, durvalumab, avelumab, cemiplimab, ipilimumab, tremelimumab, sintilimab, spartalizumab.” Observational studies and trials not offering immune checkpoint inhibitors (ICIs) or cellular immunotherapy were excluded. Eligibility criteria for each trial were reviewed to determine rate of exclusion for HIV, human immunodeficiency virus, acquired immunodeficiency, or immune deficiency. Cellular immunotherapies were defined as modified T cell, dendritic cell, NK cell, or other peripheral blood leukocyte treatments. Results: Of 1090 analyzed trials, 795 (72.9%) specifically excluded patients with HIV, and another 80 (7.3%) trials included patients with HIV only if certain criteria were met (e.g. undetectable viral load, minimum CD4+ T cell count). By tumor type, the rate of HIV exclusion ranged from 60.9% (renal cancer) to 85.7% (cervical cancer), with hematologic malignancies having a significantly higher rate of HIV exclusion than solid tumor trials (85.2% vs. 73.3%, p = 0.015). Trials combining ICIs with cellular immunotherapies were more likely to exclude HIV (N = 22, 90.9% exclusion) than trials with ICIs alone (N = 1003, 71.4% exclusion, p = 0.044). Phase I (N = 271, 73.1% exclusion, p = 0.0012), I/II (N = 165, 70.9% exclusion, p = 0.010), and II trials (N = 519, 77.5% exclusion, p < 0.0001) had higher rates of exclusion than phase III trials (N = 101, 55.4% exclusion). Conclusions: Despite ASCO and Friends of Cancer Research recommendations to include patients with HIV in cancer clinical trials, the vast majority of immunotherapy clinical trials in 2019 exclude patients with cancer and HIV.