Neoadjuvant Immunotherapy Combined Chemotherapy Followed by Surgery Versus Surgery Alone for Locally Advanced Esophageal Squamous Cell Carcinoma: A Propensity Score-Matched Study

BackgroundCombination of neoadjuvant immunotherapy and chemotherapy (nICT) is a novel treatment for locally esophageal cancer squamous cell carcinoma (ESCC). This study aimed to evaluate the potential effect of nICT on surgery safety by comparing short-term outcomes between the surgery alone group and the nICT followed by surgery group.MethodsA retrospective analysis was performed to identify patients (from January 2017 to July 2021) who underwent surgery for ESCC with or without nICT. A propensity score matching (PSM) comparison (1:1) was conducted to reduce selection biases and balance the demographic and oncologic characteristics between groups.ResultsAfter PSM, the nICT group (n = 38) was comparable to the surgery alone group (n = 38) in the following characteristics: age, sex, BMI, ASA status, smoking, tumor location, lymph node resection, clinical stage, anastomotic location, surgical approach, and surgical approach. The operation time and incidence of postoperative pneumonia in the nICT group were higher than those in the control group (p < 0.05). However, other complications and major complications were comparable between the two groups. There was no significant difference between the two groups in intraoperative blood loss, ICU stay time, postoperative hospital stay, and hospitalization cost. The 30-day mortality, 30-day readmission, and ICU readmission rates were also similar in the nICT and control groups. In the nICT group, the pathological complete response rate in primary tumor was 18.4%, and the major pathological response rate in tumor was 42.1%.ConclusionsBased on our preliminary experience, nICT followed by surgery is safe and effective with acceptable increased operation risk, manageable postoperative complications, and promising pathological response. Further multicenter prospective trials are needed to validate our results.

Download Full-text

Selected E2F2 Polymorphisms in Oral and Oropharyngeal Squamous Cell Carcinoma

BioMed Research International ◽

10.1155/2021/8098130 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Karolina Gołąbek ◽

Krzysztof Biernacki ◽

Jadwiga Gaździcka ◽

Joanna K. Strzelczyk ◽

Katarzyna Miśkiewicz-Orczyk ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Primary Tumour ◽

Critical Role ◽

Tnm Staging ◽

Oropharyngeal Squamous Cell Carcinoma ◽

Control Group ◽

Allelic Discrimination ◽

Significant Difference

Oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC) are subgroups of head and neck squamous cell carcinoma. E2F Transcription Factor 2 (E2F2) could contribute to cancer development, because it plays a critical role in many cellular processes, including the cell cycle, proliferation, differentiation, DNA damage response, and cell death. In the current study, we assessed the associations of five E2F2 polymorphisms (rs6667575, rs3218121, rs3218211, rs3218148, and rs3218203) with OSCC and OPSCC and influence on the TNM staging and grading. This is the first such survey to concern the European population. The study included 94 primary tumour samples following surgical resection from patients, whereas the control group consisted of 99 healthy individuals. We tried a matching of cases and controls for age and sample size. DNA samples were genotyped by employing the 5 ′ nuclease assay for allelic discrimination. Our results suggested that the most significant difference between the control group and the cancer group was the A/G heterozygote for rs3218121. Samples containing this genotype were mostly found in the control group. In our samples, rs6667575, rs3218121, rs3218211, and rs3218148 polymorphisms may affect the course of OSCC and OPSCC, while rs3218203 was not associated with OSCC and OPSCC. However, further studies are warranted to confirm our findings.

Download Full-text

Analysis of polymorphism in the survivin gene promoter as a potential risk factor for head and neck cancers development

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh1306304k ◽

2013 ◽

Vol 141 (5-6) ◽

pp. 304-307 ◽

Cited By ~ 7

Author(s):

Marija Kostic ◽

Nadja Nikolic ◽

Branislav Ilic ◽

Jelena Carkic ◽

Sanja Milenkovic ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Risk Factor ◽

Basal Cell Carcinoma ◽

Cancer Risk ◽

Cell Carcinoma ◽

Squamous Cell ◽

Basal Cell ◽

Control Group ◽

Survivin Gene ◽

Significant Difference

Introduction. Association studies have shown that gene polymorphisms in various classes of genes can modulate cancer risk. The -31G/C polymorphism in the promoter of survivin gene, affects the expression of the anti-apoptotic protein survivin which in turn may predispose an individual to some types of cancer. Objective. The aim of the study was to determine whether the survivin promoter -31G/C polymorphism could be a susceptibility factor for squamous cell carcinoma (SCC) of the oral cavity and basal cell carcinoma (BCC) of the skin. Methods. The DNA obtained from 88 patients with SCC, 60 patients with BCC and 111 healthy individuals was subjected to polymerase chain reaction-restriction fragment length polymorphism analysis (PCR- RFLP) in order to determine genotype and allele frequencies in patients and control groups. Logistic regression was used for cancer risk assessment. Results. The following distribution of genotypes was obtained: CC genotype 15% in the SCC group, 13% in the BCC group and 12% in controls; CG genotype 41% in SCCs, 35% in BCCs, 48% in controls; GG genotype 44% in SCCs, 52% in BCCs and 40% in controls. Allelic frequencies were as follows: G allele 0.65 in SCCs, 0.69 in BCCs and 0.64 in the control group; C allele 0.35 in SCCs, 0.31 in BCCs and 0.36 in the control group. There was no statistically significant difference in allele or genotype frequencies between the patients and controls (p>0.05). Conclusion. In Serbian population, -31G/C polymorphism in the promoter of the survivin gene cannot be considered as a risk factor for oral squamous cell carcinoma and skin basal cell carcinoma.

Download Full-text

Concurrent Chemoradiotherapy with S-1 Compared with Concurrent Chemoradiotherapy with Docetaxel and Cisplatin for Locally Advanced Esophageal Squamous Cell Carcinoma

10.21203/rs.3.rs-84169/v1 ◽

2020 ◽

Author(s):

Xi-Lei Zhou ◽

Chang-Hua Yu ◽

Wan-Wei Wang ◽

Fu-Zhi Ji ◽

Yao-Zu Xiong ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Concurrent Chemoradiotherapy ◽

Response Rate ◽

Locally Advanced ◽

Progression Free Survival ◽

Complete Response ◽

Significant Difference

Abstract Background: This retrospective study was to assess and compare the toxicity and efficacy of concurrent chemoradiotherapy (CCRT) with S-1 or docetaxel and cisplatin in patients with locally advanced esophageal squamous cell carcinoma (ESCC). Methods: Patients who had locally advanced ESCC and received CCRT with S-1 (70mg/m2 twice daily on days 1-14, every 3 weeks for 2 cycles, S-1 group) or docetaxel (25mg/m2) and cisplatin (25mg/m2) on day 1 weekly (DP group) between 2014 and 2016 were retrospectively analyzed. Treatment-related toxicities, response rate, and survival outcomes were compared between groups. Results: A total of 175 patients were included in this study (72 in the S-1 group and 103 in the DP group). Baseline characteristics were well balanced between the two groups. The incidence of grade 3-4 adverse events were significantly lower in the S-1 group than in the DP group (22.2% versus 45.6%, p = 0.002). The objective overall response rate (complete response + partial response) was 68.1% in the S-1 group, and 73.8% the DP group (p = 0.497). The 3-year overall survival was 34.7% in the S-1 group, and 38.8% in the DP group (p = 0.422). The 3-year progression free survival in the DP group was higher than that in the S-1 group but without significant difference (33.0% versus 25.0%, p = 0.275). Conclusion: CCRT with S-1 is not inferior to CCRT with docetaxel and cisplatin and is better tolerated in in elderly patients with locally advanced ESCC.

Download Full-text

Neoadjuvant immunotherapy with nivolumab and ipilimumab induces major pathological responses in patients with head and neck squamous cell carcinoma

Nature Communications ◽

10.1038/s41467-021-26472-9 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Joris L. Vos ◽

Joris B. W. Elbers ◽

Oscar Krijgsman ◽

Joleen J. H. Traets ◽

Xiaohang Qiao ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Primary Endpoint ◽

Primary Tumor ◽

Pathological Response ◽

Neck Squamous Cell Carcinoma ◽

Phase Ib ◽

Neoadjuvant Immunotherapy

AbstractSurgery for locoregionally advanced head and neck squamous cell carcinoma (HNSCC) results in 30‒50% five-year overall survival. In IMCISION (NCT03003637), a non-randomized phase Ib/IIa trial, 32 HNSCC patients are treated with 2 doses (in weeks 1 and 3) of immune checkpoint blockade (ICB) using nivolumab (NIVO MONO, n = 6, phase Ib arm A) or nivolumab plus a single dose of ipilimumab (COMBO, n = 26, 6 in phase Ib arm B, and 20 in phase IIa) prior to surgery. Primary endpoints are feasibility to resect no later than week 6 (phase Ib) and primary tumor pathological response (phase IIa). Surgery is not delayed or suspended for any patient in phase Ib, meeting the primary endpoint. Grade 3‒4 immune-related adverse events are seen in 2 of 6 (33%) NIVO MONO and 10 of 26 (38%) total COMBO patients. Pathological response, defined as the %-change in primary tumor viable tumor cell percentage from baseline biopsy to on-treatment resection, is evaluable in 17/20 phase IIa patients and 29/32 total trial patients (6/6 NIVO MONO, 23/26 COMBO). We observe a major pathological response (MPR, 90‒100% response) in 35% of patients after COMBO ICB, both in phase IIa (6/17) and in the whole trial (8/23), meeting the phase IIa primary endpoint threshold of 10%. NIVO MONO’s MPR rate is 17% (1/6). None of the MPR patients develop recurrent HSNCC during 24.0 months median postsurgical follow-up. FDG-PET-based total lesion glycolysis identifies MPR patients prior to surgery. A baseline AID/APOBEC-associated mutational profile and an on-treatment decrease in hypoxia RNA signature are observed in MPR patients. Our data indicate that neoadjuvant COMBO ICB is feasible and encouragingly efficacious in HNSCC.

Download Full-text

Phase III Study of Cisplatin With or Without Paclitaxel in Stage IVB, Recurrent, or Persistent Squamous Cell Carcinoma of the Cervix: A Gynecologic Oncology Group Study

Journal of Clinical Oncology ◽

10.1200/jco.2004.04.170 ◽

2004 ◽

Vol 22 (15) ◽

pp. 3113-3119 ◽

Cited By ~ 356

Author(s):

David H. Moore ◽

John A. Blessing ◽

Richard P. McQuellon ◽

Howard T. Thaler ◽

David Cella ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Response Rate ◽

Gynecologic Oncology ◽

Phase Iii ◽

Gynecologic Oncology Group ◽

Number Of Patients ◽

Significant Difference ◽

Stage Ivb

Purpose To determine whether cisplatin plus paclitaxel (C+P) improved response rate, progression-free survival (PFS), or survival compared with cisplatin alone in patients with stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix. Patients and Methods Eligible patients with measurable disease, performance status (PS) 0 to 2, and adequate hematologic, hepatic, and renal function received either cisplatin 50 mg/m2 or C+P (cisplatin 50 mg/m2 plus paclitaxel 135 mg/m2) every 3 weeks for six cycles. Tumor measurements and quality-of-life (QOL) assessments were obtained before each treatment cycle. Results Of 280 patients entered, 6% were ineligible. Among 264 eligible patients, 134 received cisplatin and 130 received C+P. Groups were well matched with respect to age, ethnicity, PS, tumor grade, disease site, and number of cycles received. The majority of all patients had prior radiation therapy (cisplatin, 92%; C+P, 91%). Objective responses occurred in 19% (6% complete plus 13% partial) of patients receiving cisplatin versus 36% (15% complete plus 21% partial) receiving C+P (P = .002). The median PFS was 2.8 and 4.8 months, respectively, for cisplatin versus C+P (P < .001). There was no difference in median survival (8.8 months v 9.7 months). Grade 3 to 4 anemia and neutropenia were more common in the combination arm. There was no significant difference in QOL scores, although a disproportionate number of patients (cisplatin, n= 50; C+P, n = 33) dropped out of the QOL component, presumably because of increasing disease, deteriorating health status, or early death. Conclusion C+P is superior to cisplatin alone with respect to response rate and PFS with sustained QOL.

Download Full-text

Patient-controlled Intravenous Analgesia Enhanced Recovery After Surgery by Reducing Length of Hospital Stay in Patients with Oral Squamous Cell Carcinoma Who Underwent Flap Reconstruction: A Propensity Score-matched Study

BIO Integration ◽

10.15212/bioi-2021-0018 ◽

2021 ◽

Author(s):

Haojie Yang ◽

Yingzhe Yan ◽

Qian Xie ◽

Wei Wu ◽

Zhiming Wang ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Propensity Score ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Univariate Analysis ◽

Red Blood Cell Transfusion ◽

Flap Reconstruction ◽

Significant Difference ◽

Intravenous Analgesia

Background: Patient-controlled intravenous analgesia (PCIA) is an increasingly used method to control postoperative pain. We aimed to investigate the association between PCIA and recovery after flap reconstruction in patients with oral squamous cell carcinoma (OSCC).Methods: Patients with OSCC who underwent flap reconstruction between 2016 and 2020 were reviewed (n=850). Baseline characteristics were compared between PCIA and non-PCIA groups. Propensity score matching (PSM) (1:4) was introduced to eliminate these confounding factors (n=505). Univariate analysis was performed to compare matched PCIA and non-PCIA group. Univariate and multivariate analyses were performed before and after PSM to identify factors that influenced length of stay (LOS) in hospital. The differences in characteristics of matched and unmatched groups were also compared.Results: Before PSM, the differences in flap types, smoking status, and radiotherapy history between PCIA and non-PCIA groups were statistically significant (P<0.05). After these factors were matched by PSM, LOS was 1.5 days shorter in the matched PCIA group than in the non-PCIA group (median, 10.5 versus 12.0, P=0.006). There was no significant difference in flap or medical complications, reoperations, or postoperative neutrophil-to-lymphocyte ratio (NLR) between the matched PCIA and non-PCIA groups. Postoperative glucose was lower in the matched PCIA group than in the non-PCIA group (median, 6.70 versus 7.30 mmol/L, P=0.021). Prolonged LOS was associated with postoperative PCIA, flap types, preoperative NLR, intraoperative red blood cell transfusion, fluid infusion rate over 24 h, and postoperative intensive care unit admission (P<0.05).Conclusions: Patients with OSCC using PCIA after flap reconstruction surgeries have a reduced LOS in hospital compared with those who used conventional postoperative analgesic strategies. Moreover, postoperative glucose increase was lower in the PCIA group than in the non-PCIA group.

Download Full-text

Survival After Definitive Chemoradiotherapy With Concurrent Cisplatin or Carboplatin for Head and Neck Cancer

Journal of the National Comprehensive Cancer Network ◽

10.6004/jnccn.2019.7297 ◽

2019 ◽

Vol 17 (9) ◽

pp. 1065-1073 ◽

Cited By ~ 4

Author(s):

Michael Xiang ◽

A. Dimitrios Colevas ◽

F. Christopher Holsinger ◽

Quynh-Thu X. Le ◽

Beth M. Beadle

Keyword(s):

Squamous Cell Carcinoma ◽

Propensity Score ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Propensity Score Analysis ◽

Squamous Carcinoma ◽

Concurrent Chemotherapy ◽

Definitive Chemoradiotherapy ◽

Significant Difference

Background: For definitive chemoradiotherapy (chemoRT) of head and neck squamous cell carcinoma (HNSCC), cisplatin is the preferred concurrent agent, with superiority over cetuximab for HPV-associated oropharyngeal squamous carcinoma recently shown in 2 randomized trials (RTOG 1016 and De-ESCALaTE). Patients who are not candidates for cisplatin may be treated with carboplatin instead, but its comparative efficacy is unclear. We analyzed nationwide patterns of care and cancer-specific outcomes after cisplatin- versus carboplatin-based chemoRT. Patients and Methods: Patients with locoregionally advanced (stages III–IVB according to the 6th and 7th editions of the AJCC Cancer Staging Manual) squamous cell carcinoma of the oropharynx, larynx, or hypopharynx who received definitive radiotherapy (RT) were identified in the linked SEER-Medicare database. The concurrent chemotherapy regimen was determined through corresponding Medicare claims. Death caused by HNSCC (cancer-specific mortality [CSM]) was analyzed with competing risks. Propensity score analysis and multivariable Fine-Gray regression were used to adjust for baseline differences, including age and comorbidity. Results: We identified 807 patients who received cisplatin-based chemoRT and 342 who received carboplatin-based chemoRT. Most carboplatin recipients (68%) had combination chemotherapy, predominantly with paclitaxel. Carboplatin- and cisplatin-based chemoRT had similar incidences of death attributable to HNSCC (3-year CSM, 29% vs 26%; P=.19), which persisted in propensity score–matched analysis. In addition, no significant difference in overall survival was seen in the matched cohorts. ChemoRT with either cisplatin or carboplatin was superior to RT alone and RT with concurrent cetuximab. In the multivariable model, the adjusted hazard ratio of CSM for carboplatin relative to cisplatin was 1.01 (95% CI, 0.79–1.28; P=.94). Conclusions: Definitive carboplatin-based chemoRT was equivalent to cisplatin-based therapy and superior to RT alone and RT with concurrent cetuximab. In light of recent results of the RTOG 1016 and De-ESCALaTE trials, our findings suggest that carboplatin-based regimens warrant prospective investigation as an alternative to cisplatin for patients who are not cisplatin candidates.

Download Full-text

Claudin and p53 expression in vulvar lichen sclerosus and squamous-cell carcinoma

Journal of Clinical Pathology ◽

10.1136/jclinpath-2011-200103 ◽

2011 ◽

Vol 64 (10) ◽

pp. 853-857 ◽

Cited By ~ 8

Author(s):

José Carlos Sadalla ◽

Sílvia Vanessa Lourenço ◽

Mirian Nacagami Sotto ◽

Edmund Chada Baracat ◽

Jesus Paula Carvalho

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Lichen Sclerosus ◽

Immunohistochemical Analysis ◽

Control Group ◽

Tissue Samples ◽

P53 Expression ◽

Significant Difference ◽

And Control

AimsVulvar squamous-cell carcinoma (SCC) is a rare gynaecological cancer. Vulvar SCC has been shown to develop from vulvar intraepithelial neoplasias, which are related to lichen sclerosus (LS). Most studies to date have compared vulvar SCC with LS only morphologically, but no detailed molecular analysis has been performed. The objective was to compare claudin and p53 expression in these diseases and determine if there was any association with expression and vulvar SCC progression.MethodsImmunohistochemical analysis was performed in order to determine expression of p53 and claudin 1, 2, 3, 4, 5, 7 and 11 in human vulvar tissue samples from LS, SCC and control patients.ResultsClaudin 1, 2, 3, 4 and 5 were expressed comparably in the three groups. Claudin 7 and 11 expression was significantly decreased in LS and SCC samples compared with the control group. Expression of p53 was significantly increased in SCC and LS patient samples compared with the control group.ConclusionsClaudin 7 and 11 were not expressed in LS and SCC. However, there was no significant difference in expression of any of the claudins between the LS and SCC samples. Furthermore, p53 expression is the highest in SCC patients and lowest in the control group. However, expression of p53 did not vary between samples from isolated LS and LS associated SCC patients, suggesting that increased p53 expression is not the determining factor in the progression of LS lesions to SCC.

Download Full-text

RASSF1A and KRAS Expression in Oral Leukoplakia with Dysplasia and in Squamous Cell Carcinoma

Journal of Dentistry & Oral Disorders ◽

10.26420/jdentoraldisord.2021.1154 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Costa V ◽

◽

El Achkar VNR ◽

Ribeiro MP ◽

Tristao SS ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Early Stage ◽

Critical Role ◽

Disease Free Survival ◽

Oral Leukoplakia ◽

Control Group ◽

Significant Difference ◽

Kras Protein

The aim of this study is to investigate the role of RASSF1A and KRAS protein immunoexpression in Oral Leukoplakia with Epithelial Dysplasia (OLD) and in Oral Squamous Cell Carcinoma (OSCC). Immunohistochemical staining for RASSF1A and KRAS was performed and a semiquantitative analysis was applied to samples of the Control Group (CG, n=20), OLD (n=39), and OSCC (n=100). No significant difference was observed between RASSF1A immunoexpression and OLP and OSCC groups (p>0.05). KRAS expression was higher in OSCC than in OLP and CG (p<0.05). No association was observed between RASSF1A or KRAS expression and alcohol/tobacco use or clinicopathological features (p>0.05) in the OSCC group. Also, patients with OSCC who presented KRAS overexpression had a worse disease-free survival rate (p=0.04). RASSF1A expression was similar in OLD and OSCC groups, suggesting that it plays a critical role in the early stage of OSCC. KRAS expression was higher in OSCC when compared with normal and dysplastic tissues, showing that KRAS expression increases with malignant progression.

Download Full-text

First-line paclitaxel and cisplatin in patients with advanced squamous-cell carcinoma of the esophagus

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.15157 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 15157-15157

Author(s):

X. Zhang ◽

L. Shen ◽

J. Li ◽

Y. Li ◽

J. Li ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Median Survival ◽

Squamous Cell ◽

Median Overall Survival ◽

Overall Response Rate ◽

Response Rate ◽

Carcinoma Of The Esophagus ◽

Significant Difference ◽

Promising Treatment

15157 Objectives: To evaluate response rate, survival and toxicities of paclitaxel/cisplatin combination in patients with advanced or metastatic squamous-cell carcinoma of the esophagus. Methods: Thirty-nine patients with definite measurable indices and no prior chemotherapy were enrolled. Patients were treated with paclitaxel 175 mg/m2 by 2-hour infusion day 1 and cisplatin 75 mg/m2 infusion day 1. Treatment was repeated every 21 days. Results: Thirty-nine patients were enrolled. 35 patients were eligible to be evaluated for response. The overall response rate was 48.6% (95% confidence interval [CI], 0.31∼0.65) with complete and partial response rates of 2.8% and 45.7%, respectively. The median time to progression(TTP) was 7 months, and median survival time of all patients was 13 months. There was a significant difference in median overall survival between the patients who had received responding versus those who had not (p = 0.006). Median survival was 17 (95% CI, 11.9–22.0) and 10 months (95% CI, 7.6–12.35) for responding patients and non-responding patients, respectively. The 1-yr survival probability was 39%. Relief of dysphagia and pain were observed in 86.2% of the all patients. The most common toxicities were neutropenia and alopecia. There were no grade 4 clinical toxicities and treatment-related deaths were recorded in all patients. Conclusions: Paclitaxel and cisplatin is a promising treatment for patients with squamous-cell carcinoma of the esophagus. The toxicity of this regimen is within acceptable range. No significant financial relationships to disclose.

Download Full-text