Retrospective analysis of outcomes of cisplatin (CDDP) versus non cisplatin based treatment regimens for concurrent chemoradiotherapy (CCRT) in locally advanced squamous cell head and neck cancer (LA-SCCHN).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17564-e17564
Author(s):  
Syed Muhammad Mushtaq Ashraf ◽  
Ali Mehmood Raufi ◽  
William R Barnett ◽  
James Benjamin Williams ◽  
Roland T. Skeel
Keyword(s):  
Overall Survival ◽  
Head And Neck ◽  
Squamous Cell ◽  
Concurrent Chemoradiotherapy ◽  
Locally Advanced ◽  
Intensity Modulated Radiation Therapy ◽  
Standard Of Care ◽  
Smoking History ◽  
Treatment Regimens ◽  
Significant Difference

e17564 Background: Different dosing schedules of CDDP are being used as standard of care for CCRT in LA-SCCHN, but there are no adequately powered trials to directly compare other non-CDDP regimens with CDDP to identify the optimal CCRT regimen. Methods: After obtaining IRB approval, we reviewed medical records from hospital tumor registry for consecutive patients with LA-SCCHN to retrieve data regarding demographics, diagnosis and treatment with definitive CCRT between December 2012 and December 2016. All patients had followed up for at least 24 months after completion of treatment. Results: 155 patients were included in the analysis. They fell into 2 groups: 89 (57.4%) had been administered CDDP and 66 (42.6%) received non-CDDP based regimen. In the latter group, 30 (45.5%) received cetuximab, 30 (45.5%) received carboplatin with paclitaxel, 1 (1.5%) received carboplatin with 5-fluorouracil and 5 (7.6%) received carboplatin alone. The majority of patients in both groups had oropharyngeal involvement, approximately 65%. All patients completed treatment with intensity-modulated radiation therapy. Median age was 57 years in CDDP group and 67 years in non-CDDP group. Patients in both groups were predominantly male, Caucasian, with positive smoking history. 67% patients in CDDP & 59% in non-CDDP group were HPV positive. The 2-year overall survival (OS) from initiation of treatment was 73.9% in CDDP and 62.1% in non-CDDP group (hazard ratio = 1.63, 95% CI 0.92 – 2.87, p = 0.092). Comparing non-CDDP regimens with CDDP, cetuximab appeared to confer better 2 year OS in HPV positive patients (HR 0.63, 95% CI 0.40 – 0.98, p = 0.040). Median time-to-treatment failure was 33 months in CDDP group and 24 months in non CDDP group. Conclusions: In this retrospective comparison, there was no significant difference in the 2 year overall survival in patients with locally advanced squamous cell head and neck cancers being treated with cisplatin based concurrent chemoradiotherapy regimen versus a non-cisplatin based regimen.

Carboplatin versus cetuximab chemoradiation in cisplatin ineligible locally advanced head and neck squamous cell carcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18555-e18555
Author(s):  
Kannan Thanikachalam ◽  
Jayasree Krishnan ◽  
Farzan Siddiqui ◽  
Haythem Y. Ali ◽  
Jawad Sheqwara
Keyword(s):  
Head And Neck ◽  
Squamous Cell ◽  
Randomized Clinical Trials ◽  
Single Agent ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Hpv Infection ◽  
Entire Group ◽  
P Value ◽  
Significant Difference

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.

scholarly journals Expression of the Extracellular Sulfatase SULF2 Affects Survival of Head and Neck Squamous Cell Carcinoma Patients

2021 ◽  
Vol 10 ◽  
Author(s):  
Yang Yang ◽  
Jaeil Ahn ◽  
Rekha Raghunathan ◽  
Bhaskar V. Kallakury ◽  
Bruce Davidson ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Hpv Infection ◽  
Neck Squamous Cell Carcinoma ◽  
Therapeutic Interventions ◽  
Tumor Tissues ◽  
Significant Difference

Sulfation of heparan sulfate proteoglycans (HSPG) regulates signaling of growth factor receptors via specific interactions with the sulfate groups. 6-O-Sulfation of HSPG is an impactful modification regulated by the activities of dedicated extracellular endosulfatases. Specifically, extracellular sulfatase Sulf-2 (SULF2) removes 6-O-sulfate from HS chains, modulates affinity of carrier HSPG to their ligands, and thereby influences activity of the downstream signaling pathway. In this study, we explored the effect of SULF2 expression on HSPG sulfation and its relationship to clinical outcomes of patients with head and neck squamous cell carcinoma (HNSCC). We found a significant overexpression of SULF2 in HNSCC tumor tissues which differs by tumor location and etiology. Expression of SULF2 mRNA in tumors associated with human papillomavirus (HPV) infection was two-fold lower than in tumors associated with a history of tobacco and alcohol consumption. High SULF2 mRNA expression is significantly correlated with poor progression-free interval and overall survival of patients (n = 499). Among all HS-related enzymes, SULF2 expression had the highest hazard ratio in overall survival after adjusting for clinical characteristics. SULF2 protein expression (n = 124), determined by immunohistochemical analysis, showed a similar trend. The content of 6-O-sulfated HSPG, measured by staining with the HS3A8 antibody, was higher in adjacent mucosa compared to tumor tissue but revealed no difference based on SULF2 staining. LC-MS/MS analysis showed low abundance of N-sulfation and O-sulfation in HS but no significant difference between SULF2-positive and SULF2-negative tumors. Levels of enzymes modifying 6-O-sulfation, measured by RT-qPCR in HNSCC tumor tissues, suggest that HSPG sulfation is carried out by the co-regulated activities of multiple genes. Imbalance of the HS modifying enzymes in HNSCC tumors modifies the overall sulfation pattern, but the alteration of 6-O-sulfate is likely non-uniform and occurs in specific domains of the HS chains. These findings demonstrate that SULF2 expression correlates with survival of HNSCC patients and could potentially serve as a prognostic factor or target of therapeutic interventions.

scholarly journals Induction Chemotherapy Followed by Cetuximab Radiotherapy Is Not Superior to Concurrent Chemoradiotherapy for Head and Neck Carcinomas: Results of the GORTEC 2007-02 Phase III Randomized Trial

2018 ◽  
Vol 36 (31) ◽  
pp. 3077-3083 ◽  
Author(s):  
Lionnel Geoffrois ◽  
Laurent Martin ◽  
Dominique De Raucourt ◽  
Xu Shan Sun ◽  
Yungan Tao ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Induction Chemotherapy ◽  
Squamous Cell ◽  
Concurrent Chemoradiotherapy ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Phase Iii ◽  
Free Survival

Purpose Both concurrent chemoradiotherapy (CT-RT) and cetuximab radiotherapy (cetux-RT) have been established as the standard of care for the treatment of locally advanced squamous cell carcinoma of the head and neck. It was not known whether the addition of induction chemotherapy before cetux-RT could improve outcomes compared with standard of care CT-RT. Patients and Methods The current trial was restricted to patients with nonmetastatic N2b, N2c, or N3 squamous cell carcinoma of the head and neck and fit for taxotere, cisplatin, fluorouracil (TPF). Patients were randomly assigned to receive three cycles of TPF followed by cetux-RT versus concurrent carboplatin fluorouracil and RT as recommended in National Comprehensive Cancer Network guidelines. The trial was powered to detect a hazard ratio (HR) of 0.66 in favor of TPF plus cetux-RT for progression-free survival at 2 years. The inclusion of 180 patients per arm was needed to achieve 80% power at a two-sided significance level of .05. Results Between 2009 and 2013, 370 patients were included. All patients and tumors characteristics were well balanced between arms. There were more cases of grade 3 and 4 neutropenia in the induction arm, and the induction TPF was associated with 6.6% treatment-related deaths. With a median follow-up of 2.8 years, 2-year progression-free survival was not different between both arms (CT-RT, 0.38 v TPF + cetux-RT, 0.36; HR, 0.93 [95% CI, 0.73 to 1.20]; P = .58). HR was 0.98 (95% CI, 0.74 to 1.3; P = .90) for locoregional control and 1.12 (95% CI, 0.86 to 1.46; P = .39) for overall survival. These effects were observed regardless of p16 status. The rate of distant metastases was lower in the TPF arm (HR, 0.54 [95% CI, 0.30 to 0.99]; P = .05). Conclusion Induction TPF followed by cetux-RT did not improve outcomes compared with CT-RT in a population of patients with advanced cervical lymphadenopathy.

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