The comparison between weekly and three-weekly cisplatin delivered concurrently with radiotherapy for patients with postoperative high-risk squamous cell carcinoma of the oral cavity

Adjuvant chemoradiation (CRT), with high-dose cisplatin remains standard treatment for oral cavity squamous cell carcinoma (OCSCC) with high-risk pathologic features. We evaluated outcomes associated with different cisplatin dosing and schedules, concurrent with radiation (RT), and the effect of cumulative dosing of cisplatin. An IRB-approved collaborative database of patients (pts) with primary OCSCC (Stage I–IVB AJCC 7th edition) treated with primary surgical resection between January 2005 and January 2015, with or without adjuvant therapy, was established from six academic institutions. Patients were categorized by cisplatin dose and schedule, and resultant groups compared for demographic data, pathologic features, and outcomes by statistical analysis to determine disease free survival (DFS) and freedom from metastatic disease (DM). From a total sample size of 1282 pts, 196 pts were identified with high-risk features who were treated with adjuvant CRT. Administration schedule of cisplatin was not significantly associated with DFS. On multivariate (MVA), DFS was significantly better in patients without perineural invasion (PNI) and in those receiving ≥200 mg/m2 cisplatin dose (p < 0.001 and 0.007). Median DFS, by cisplatin dose, was 10.5 (<200 mg/m2) vs. 20.8 months (≥200 mg/m2). Our analysis demonstrated cumulative cisplatin dose ≥200 mg/m2 was associated with improved DFS in high-risk resected OCSCC pts.

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Phase II Feasibility Trial of Adjuvant Chemoradiotherapy with 3-weekly Cisplatin for Japanese Patients with Post-operative High-risk Squamous Cell Carcinoma of the Head and Neck

Japanese Journal of Clinical Oncology ◽

10.1093/jjco/hys128 ◽

2012 ◽

Vol 42 (10) ◽

pp. 927-933 ◽

Cited By ~ 25

Author(s):

N. Kiyota ◽

M. Tahara ◽

S. Okano ◽

M. Kawashima ◽

K. Matsuura ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

High Risk ◽

Cell Carcinoma ◽

Head And Neck ◽

Phase Ii ◽

Squamous Cell ◽

Japanese Patients ◽

Feasibility Trial ◽

Adjuvant Chemoradiotherapy ◽

Weekly Cisplatin

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Postoperative radiotherapy for patients at high risk of recurrence of oral cavity squamous cell carcinoma

The Laryngoscope ◽

10.1002/lary.24938 ◽

2014 ◽

Vol 125 (3) ◽

pp. 630-635 ◽

Cited By ~ 12

Author(s):

Michael P. Herman ◽

Roi Dagan ◽

Robert J. Amdur ◽

Christopher G. Morris ◽

John W. Werning ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

High Risk ◽

Oral Cavity ◽

Cell Carcinoma ◽

Squamous Cell ◽

Postoperative Radiotherapy ◽

Risk Of Recurrence

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Characteristics of the course of squamous cell carcinoma of the oral cavity depending on the HPV status.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e17579 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e17579-e17579

Author(s):

Pavel V. Svetitskiy ◽

Tatiana A. Zykova ◽

Viktoriya L. Volkova ◽

Irina V. Aedinova

Keyword(s):

Squamous Cell Carcinoma ◽

High Risk ◽

Oral Cavity ◽

Cell Carcinoma ◽

Squamous Cell ◽

Hpv Infection ◽

Lower Grade ◽

Tumor Tissues ◽

Hpv Status ◽

Formalin Fixed Paraffin Embedded

e17579 Background: HPV infection has a positive prognostic value in the treatment of patients with oropharyngeal squamous cell carcinoma. The purpose of the study was to evaluate the effect of HPV status on the course of oral cavity cancer. Methods: Formalin-fixed paraffin-embedded tumor tissues were studied in 34 patients with cancer of the floor of the mouth aged 47-85 years, 3 (8.8%) women and 31 (91.2%) men. All patients had histologically verified squamous cell carcinoma: stage (st) I in 1 (2.9%), II st - 8 (23.5%), III st - 12 (35.3%), IV st - 13 (38.3%); G1 in 15 (44.1%), G2 - 19 (55.9%). HPV DNAs were detected by Real-time PCR. Results: HPV DNAs were found in 12 (35.3%) samples of tumor tissues, including type 6 in 1 (2.9%), 11 in 3 (8.8%), 16 in 6 (17.6%), 35 in 1 (2.9%), 16+35 in 1 (2.9%). HPV+ tumors were more often in women (66.7% vs 32.3% in men), but high-risk HPV types were detected in men only - 8 (25.8%). Among patients aged 47-55 years, HPV+ tumor status was detected in 4 (33.3%), 56-65 years in 7 (53.8%), 66 years and older - in 1 (11.1%). In st I, no HPV+ tumors were observed; st II - 3 (37.5%) HPV+ tumors, low-risk in all; st III - 3 (25%) HPV+ patients, including high-risk in 2 (16.7%); st IV - 6 (46.2%) HPV+ samples, high-risk in all. G1 tumors: HPV+ in 7 (46.7%), HPV- in 8 (53.3%) patients; G2 tumors: HPV+ in 5 (26.3%), HPV- in 14 (73.7%) patients. Among patients with HPV+ tumors, metastases were observed in 5 (41.7%), no metastases - in 7 (58.3%); for patients with HPV- tumors, the values were 12 (54.5%) and 10 (45.5%) respectively. 4 (33.3%) patients with HPV+ tumors died, while 8 (66.7%) survived; for patients with HPV- tumors, the values were 12 (54.5%) and 10 (45.5%) respectively. Conclusions: The development of squamous cell carcinoma of the oral cavity was multidirectional and depended on the HPV status. HPV+ tumors, especially high-risk ones, were more often registered in stages III and IV. HPV+ tumors were more often lower-grade ones and less often metastasized; the mortality rate among patients with HPV+ tumors was lower than with HPV- ones.

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A study of chemoradiotherapy with high dose cisplatin for postoperative high-risk squamous cell carcinoma of oral cavity

Annals of Oncology ◽

10.1093/annonc/mdv472.134 ◽

2015 ◽

Vol 26 ◽

pp. vii135

Author(s):

Toshihiro Arai ◽

Yoshihide Ota ◽

Takayuki Aoki ◽

Mitsunobu Otsuru

Keyword(s):

Squamous Cell Carcinoma ◽

High Risk ◽

Oral Cavity ◽

Cell Carcinoma ◽

Squamous Cell ◽

High Dose

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Do high-risk human papillomaviruses cause oral cavity squamous cell carcinoma?

Oral Oncology ◽

10.1016/j.oraloncology.2014.11.011 ◽

2015 ◽

Vol 51 (3) ◽

pp. 229-236 ◽

Cited By ~ 45

Author(s):

H. Mirghani ◽

F. Amen ◽

F. Moreau ◽

J. Lacau St Guily

Keyword(s):

Squamous Cell Carcinoma ◽

High Risk ◽

Oral Cavity ◽

Cell Carcinoma ◽

Squamous Cell ◽

Human Papillomaviruses

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High-Risk TP53 Mutations Are Associated with Extranodal Extension in Oral Cavity Squamous Cell Carcinoma

Clinical Cancer Research ◽

10.1158/1078-0432.ccr-17-0721 ◽

2018 ◽

Vol 24 (7) ◽

pp. 1727-1733 ◽

Cited By ~ 12

Author(s):

Vlad C. Sandulache ◽

Chieko Michikawa ◽

Pranav Kataria ◽

Frederico O. Gleber-Netto ◽

Diana Bell ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

High Risk ◽

Oral Cavity ◽

Cell Carcinoma ◽

Squamous Cell ◽

Tp53 Mutations ◽

Extranodal Extension

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Phase II/III trial of post-operative chemoradiotherapy comparing 3-weekly cisplatin with weekly cisplatin in high-risk patients with squamous cell carcinoma of head and neck (JCOG1008).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.6502 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 6502-6502 ◽

Cited By ~ 6

Author(s):

Naomi Kiyota ◽

Makoto Tahara ◽

Hirofumi Fujii ◽

Tomoko Yamazaki ◽

Hiroki Mitani ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

High Risk ◽

Cell Carcinoma ◽

Head And Neck ◽

Phase Ii ◽

Squamous Cell ◽

Standard Treatment ◽

Phase Iii ◽

Risk Patients ◽

Weekly Cisplatin

6502 Background: The standard treatment for post-operative high-risk patients (pts) with locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) is chemoradiotherapy with 3-weekly cisplatin (CDDP) (100 mg/m2, q3wk, 66 Gy/33Fr; 3-weekly CDDP+RT). However, one concern with 3-weekly CDDP+RT is insufficient CDDP compliance due to high-dose-related toxicities. Weekly CDDP+RT (40 mg/m2, qwk, 66 Gy/33Fr; weekly CDDP+RT) is an alternative regimen with better compliance. Here, we conducted a phase II/III trial of weekly CDDP+RT in post-operative high-risk LA-SCCHN. Methods: This is a multi-institutional randomized phase II/III trial to confirm the non-inferiority of weekly CDDP+RT (Arm B) compared with 3-weekly CDDP+RT (Arm A). The trial enrolled pts aged 20-75 years with post-operative high-risk features (microscopically positive margin and/or extranodal extension) and ECOG-PS 0-1. Pts were randomized in a 1:1 ratio to Arm A or Arm B. Primary endpoint of phase II was the proportion of treatment completion and that of phase III was overall survival (OS). A non-inferiority margin of hazard ratio (HR) was set at 1.32. Results: Between Oct 2012 and Dec 2018, 261 pts were enrolled (Arm A 132 pts, Arm B 129 pts). At the planned second interim analysis in phase III with 76/161 events, the Data and Safety Monitoring Committee recommended terminating the trial and publishing the results because the statistical boundary for OS non-inferiority had met the pre-specified stop criteria. With a median follow-up of 2.2 years in all randomized pts, 3-year OS was 59.1% in Arm A and 71.6% in Arm B with a HR of 0.69 (99.1% CI, 0.374-1.273 [ < 1.32], one-sided p for non-inferiority = 0.00272 < 0.00433). 3-year RFS was 53.0% in Arm A and 64.5% in Arm B with a HR of 0.71 (95% CI, 0.48-1.06). Regarding acute adverse events, neutropenia (≥ grade 3), increased creatinine (≥ grade 2), hearing impairment (≥ grade 2) and mucositis (≥ grade 2) occurred in 48.8%, 8.5%, 7.8% and 55.0% in Arm A and 35.3%, 5.7%, 2.5% and 59.0% in Arm B, respectively. For compliance, median total dose of CDDP was 280 mg/m2 (IQR, 250-299) in Arm A and 239 mg/m2 (IQR, 199-277) in Arm B. Total radiation dose was 66 Gy (IQR, 66-66) in both arms. Proportion of treatment completion was 93.2% in Arm A and 86.8% in Arm B. Conclusions: Weekly CDDP+RT is non-inferior to 3-weekly CDDP+RT for post-operative high-risk LA-SCCHN pts and has a favorable toxicity profile. Weekly CDDP+RT should be considered the new standard treatment option for these pts. Clinical trial information: 000009125 .

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