Postoperative concurrent chemoradiation (CCRT) for non-squamous cell carcinoma (NSCCA) of head and neck.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e17582-e17582
Author(s):  
Lucksamon Thamlikitkul ◽  
Janjira Petsuksiri ◽  
Suthinee Ithimakin
Keyword(s):  
High Risk ◽  
Head And Neck ◽  
Squamous Cell ◽  
Disease Free Survival ◽  
Primary Site ◽  
Stage I ◽  
Secondary Outcome ◽  
Curative Surgery ◽  
Cervical Lymph Nodes ◽  
Significant Difference

e17582 Background: Surgery is the mainstay of treatment for resectable non-metastatic NSCCA of head and neck. Postoperative radiation (RT) is delivered to patients (pt) with high risk for recurrence. Unlike the squamous cell counterpart where survival advantage from adding chemotherapy (CMT) as a radio-sensitizer is evident, the benefit of CCRT is uncertain in NSCCA pt. We hypothesized that CCRT would improve disease free survival (DFS), comparing to RT alone. Methods: NSCCA of head and neck pt who underwent curative surgery and RT at Siriraj hospital from 2006 to 2015 were included in this retrospective study. Patients with residual tumor after surgery or neuroendocrine histology were excluded. The primary outcome was DFS. The secondary outcome was overall survival (OS). Results: We included 139 pt, 99 (71.2%) had RT while 40 (28.8%) had CCRT. Baseline characteristics, including age, gender, primary site, histology and radiation dose were similar between 2 groups. Salivary gland was the most common primary site (67.6%). The most common histology was adenoid cystic carcinoma (35.3%), followed by mucoepidermoid carcinoma (25.9%). Patients who received RT alone had earlier stage (Stage I 29.3%, Stage IVa 14.1%), compared to CCRT group (Stage I 7.7%, Stage IVa 38.5%), p = 0.003. High risk features (positive margin, extranodal extension or ≥ 2 cervical lymph nodes metastasis) were found in 42% and 62% of pt with RT and CCRT, respectively (p = 0.03). In CCRT group, 92% of pt received cisplatin every 3 weeks during RT period. With the median follow-up time of 54.9 months, 3-year DFS was 79.4% and 79.5% in RT and CCRT groups, respectively (p = 0.22). There was no significant difference in 3-year OS between RT and CCRT groups (89.2% vs 89.9%, p = 0.76). Among pt with high-risk features (n = 67, 48.2%), 3-year DFS and OS were not significantly different between treatment groups. However, among pt without high-risk features, 3-year DFS in RT group was significantly higher than CCRT group (84.8% vs 79.0%, p = 0.04). Conclusions: This study demonstrates no survival benefit from adding concurrent CMT to RT following curative surgery in NSCCA of head and neck. Moreover, addition of CMT may be detrimental in pt without high-risk features.

809 Phase 2 trial of neoadjuvant and adjuvant PD-1 checkpoint blockade in local-regionally advanced, resectable HNSCC indicates pathological response is associated with high disease-free survival

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A859-A860
Author(s):  
Trisha Wise-Draper ◽  
Shuchi Gulati ◽  
Vinita Takiar ◽  
Sarah Palackdharry ◽  
Francis Worden ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Disease Free Survival ◽  
Pathological Response ◽  
Intermediate Risk ◽  
Free Survival ◽  
Disease Free

BackgroundPatients with newly diagnosed, resected, head and neck squamous cell carcinoma (HNSCC) with high-risk (positive margins, extracapsular spread [ECE]) or intermediate-risk pathological features have an estimated 1-year disease free survival (DFS) of 65% and 69%, respectively.1 PD-1/PD-L1 immune checkpoint blockade has improved survival of patients with recurrent/metastatic HNSCC, and preclinical models indicate radiation upregulates PD-L1.2 Therefore, we hypothesized that pre and post-operative administration of the PD-1 inhibitor pembrolizumab would improve 1-year DFS for patients with resectable, loco-regionally advanced (clinical T3/4 and/or ≥2 nodal metastases) HNSCC (NCT02641093).MethodsEligible patients received pembrolizumab (200 mg I.V. x 1) 1-3 weeks before resection. Adjuvant pembrolizumab (q3 wks x 6 doses) was administered with weekly cisplatin (40mg/m2 X 6) and radiation (60-66Gy) for those with high-risk features and radiation alone for patients with intermediate-risk features. The primary endpoint was DFS, which was compared by log-rank test to historical controls (RTOG 9501). Evidence of pathological response to neoadjuvant pembrolizumab was evaluated by comparing pre- and post-surgical tumor specimens for treatment effect (TE) defined as tumor necrosis and/or histiocytic inflammation and giant cell reaction to keratinaceous debris. Response was classified as none (NPR, <20%), partial (PPR, ≥20% and <90%) and major (MPR, ≥90%) pathological response. Gene expression analysis in paired tumor specimens was evaluated by Nanostring.ResultsSixty-six of 84 enrolled patients had received adjuvant pembrolizumab and therefore were evaluable for DFS at the time of interim analysis. Patient characteristics included: median age 59 (range of 27 – 76) years; 30% female; 85% oral cavity, 11% larynx, and 2% human papillomavirus negative oropharynx; 85% clinical T3/4 and 68% ≥2N; 41(51%) high-risk (positive margins, 49%; ECE, 80%). At a median follow-up of 16 months, 1-year DFS was 66% (95%CI 0.48-0.84) in the high-risk group (p=1) and 91% (95%CI 0.79-1) in the intermediate-risk group (versus 69% in RTOG 9501, p=0.05) (figure 1). Among 70 patients evaluable for pathological response, TE was scored as NPR in 40, PPR in 27, and MPR in 3 patients. Patients with pathological response that were also evaluable for DFS (PPR + MPR) had significantly improved 1-year DFS when compared with those with NPR (100% versus 57%, p=0.0033; HR = 0.18 [95%CI 0.05-0.64]) (figure 2). PPR/MPR was associated with robust macrophage infiltration via Nanostring.Abstract 809 Figure 1Disease Free Survival by Pathological RiskPatients were stratified by pathological risk and DFS was measuredAbstract 809 Figure 2Disease Free Survival by Pathological ResponsePaired patient tissue was assessed for treatment effect (TE) and patients with greater than or equal to 20% TE were considered to have developed pathological response. Patients were stratified into responders and non-responders and DFS was determined.ConclusionsNeoadjuvant and adjuvant pembrolizumab led to high DFS in intermediate-risk, but not high-risk, resected HNSCC patients. Pathological response to neoadjuvant pembrolizumab was associated with high 1-year DFS.AcknowledgementsWe’d like to acknowledge the UCCC clinical trials office for their hard work on this study as well as our patients. We’d also like to acknowledge Merck & Co, Inc as they partially funded the clinical trial.Trial RegistrationNCT02641093Ethics ApprovalThis study was approved by the University of Cincinnati IRB with approval number 2015-6798ReferencesCooper JS, Pajak TF, Forastiere AA, et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 2004;350(19):1937-1944. doi:10.1056/NEJMoa032646Oweida A, Lennon S, Calame D, et al. Ionizing radiation sensitizes tumors to PD-L1 immune checkpoint blockade in orthotopic murine head and neck squamous cell carcinoma. Oncoimmunology2017;6(10):e1356153. Published 2017 Aug 3. doi:10.1080/2162402X.2017.1356153

Diagnostic evaluation of squamous cell carcinoma metastatic to cervical lymph nodes from an unknown head and neck primary site

Head & Neck ◽  
1998 ◽  
Vol 20 (8) ◽  
pp. 739-744 ◽  
Author(s):  
William M. Mendenhall ◽  
Anthony A. Mancuso ◽  
James T. Parsons ◽  
Scott P. Stringer ◽  
Nicholas J. Cassisi
Keyword(s):  
Squamous Cell Carcinoma ◽  
Lymph Nodes ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Primary Site ◽  
Diagnostic Evaluation ◽  
Cervical Lymph Nodes

scholarly journals Early Postoperative Paclitaxel Followed by Concurrent Paclitaxel and Cisplatin With Radiation Therapy for Patients With Resected High-Risk Head and Neck Squamous Cell Carcinoma: Report of the Phase II Trial RTOG 0024

2009 ◽  
Vol 27 (28) ◽  
pp. 4727-4732 ◽  
Author(s):  
David I. Rosenthal ◽  
Jonathan Harris ◽  
Arlene A. Forastiere ◽  
Randal S. Weber ◽  
John A. Ridge ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
High Risk ◽  
Head And Neck ◽  
Squamous Cell ◽  
Concurrent Chemoradiotherapy ◽  
Disease Free Survival ◽  
Locoregional Control ◽  
Free Survival ◽  
Positive Margins ◽  
Disease Free

Purpose We sought to improve outcomes for patients with high-risk head and neck squamous cell cancer (HNSCC) after surgical resection by testing the feasibility and safety of early postoperative chemotherapy followed by concurrent chemoradiotherapy. Patients and Methods Eligible patients had resected, stages III to IV HNSCC with positive margins, extracapsular nodal extension, or multiple positive nodes. Paclitaxel (80 mg/m2) was given once weekly during postoperative weeks 2, 3, and 4 and was given before radiation therapy (RT). Paclitaxel (30 mg/m2) and cisplatin (20 mg/m2) were given once weekly during the last 3 weeks of RT (60 Gy over 6 weeks, beginning 4 to 5 weeks after surgery). The primary end points were treatment safety and tolerability compared with concurrent cisplatin (100 mg/m2 every 3 weeks) and RT, as tested in Radiation Therapy Oncology Group trial RTOG 9501. Results The median follow-up time for the 70 patients enrolled was 3.3 years (range, 0.6 to 4.4 years) for surviving patients. Tolerability of all treatment components was comparable to that of RTOG 9501 treatment, which is the current standard of care (compliance rate, 75%; 95% CI, 63% to 85%). One patient died, and seven patients experienced grade 4 nonhematologic toxicities. Rates of locoregional control, disease-free survival, and overall survival exceeded those of RTOG 9501 after adjustment for important prognostic variables (ie, positive margins, extracapsular extension, primary site, and performance status). Conclusion Chemotherapy soon after surgery followed by concurrent chemoradiotherapy therapy was feasible; tolerance was in line with standard postoperative chemoradiotherapy; and this regimen led to excellent rates of locoregional control and disease-free survival.

Single institute analysis of squamous cell carcinoma of the head and neck treated with concurrent chemoradiation with either cisplatin versus cetuximab.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17571-e17571
Author(s):  
Il Seok Jeong ◽  
Matthew Kim ◽  
Anthony L. Nguyen ◽  
Huan Mo ◽  
Bruce Hayton ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Smoking Status ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Concurrent Chemoradiation ◽  
First Line ◽  
Significant Difference

e17571 Background: Squamous cell carcinoma of the head and neck (SCCHN) is currently the sixth most common cancer in the world and is linked to tobacco, alcohol and human papillomavirus (HPV). Cisplatin (Cs)-based concurrent chemoradiation is currently the standard treatment for locally advanced disease with a desire for organ preservation. In 2006, cetuximab (Cx) with radiation was approved as another option for this indication. We performed a single institute retrospective analysis to explore the difference in efficacy between Cs and Cx regimens with respect to P16 and smoking status. Methods: We retrospectively reviewed pts in Loma Linda University Medical Center (LLUMC) with locally advanced SCCHN who received concurrent chemoradiation with either Cx or Cs as first-line treatment from 2006 to present. We excluded patients with nasopharyngeal cancers, and patients having surgery as first line of treatment. Overall survival (OS) and disease free survival (DFS) with respect to p16 status and smoking status are the two primary endpoints. Results: Based on our study criteria, 115 out of 1545 screened pts qualified. The average age at diagnosis was 60 years. 75.7% were males and 24.3% were females. Median follow-up is 26 months. There are overall 55 DFS events and 23 OS events. Comparing between smokers (S, n = 44) and non-smokers (NS, n = 42), there is no significant difference in OS (NS: HR = 0.73 [0.28-1.92], p = 0.52) while the DFS was significantly better in the NS (NS: HR = 0.53 [0.29-0.98], p = 0.043). The overall median OS of the P16-pos pts (n = 49) is not reached while that of P16-neg pts (n = 12) is 36 mo (P16-neg: HR = 6.431 [1.71-24.13], p = 0.0058). The overall median DFS of the P16-pos pts is not reached while that of P16-neg pts is 6.5 mo (P16-neg: HR = 5.39 [2.32-12.54], p < 0.001). Overall, the median OS of Cx is 132 mo while that of Cs is not reached (Cs: HR = 0.38 [0.16-0.90], p = 0.027). The median DFS is 30 mo for Cs and 25 mo for Cx. Within P16-pos population, there are 4 OS events in Cx (n = 18) while 0 in Cs (n = 31)(p = 0.0062, favors Cs); there are 5 DFS events in Cx while 9 in Cs (Cs: HR = 1.17 [0.39-3.51], p = 0.78). The median OS and DFS for both groups are not reached. Conclusions: Our analysis of retrospective single institute data shows that positive P16 significantly associates with better OS. These findings are consistent with previous reports. Compared to Cx, the Cs regimen significantly associates with a better OS but not DFS in both overall and P16-pos populations.

Comparison of the seventh and eighth editions of the American Joint Committee on Cancer (AJCC) staging for oropharyngeal squamous cell carcinomas (OPSCC): A Surveillance, Epidemiology and End Results Program (SEER) database analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17538-e17538
Author(s):  
Sumita Trivedi ◽  
Haocan Song ◽  
Yuan Liu ◽  
Conor Ernst Steuer ◽  
William Stokes ◽  
...  
Keyword(s):  
Overall Survival ◽  
Head And Neck ◽  
Squamous Cell ◽  
Disease Free Survival ◽  
Squamous Cell Carcinomas ◽  
Stage I ◽  
Seer Database ◽  
Free Survival ◽  
Ajcc Staging ◽  
Disease Free

e17538 Background: The recently released eighth edition of the American Joint Committee on Cancer (AJCC) Staging Manual, Head and Neck Section, incorporates significant changes to the prior seventh edition. The changes reflect the improved understanding of tumor biology, prognostic factors and molecular markers that effect outcomes in Head and Neck cancers. A key update restages OPSCC by human papilloma virus (HPV) positive and negative cancers as data demonstrated that these tumors have significantly different biology and outcomes. Methods: Using SEER data from 2004 – 2014, we identified male patients with squamous cell carcinomas of the tonsil, base of tongue and soft palate aged between 21 and 64 years old (those clinical characterizes were considered as surrogate markers for HPV positive status). We classified them by the AJCC 8th edition staging for HPV positive OPSCC and by AJCC 7th edition staging. The prediction performance by two staging editions were compared regarding overall survival (OS) and Disease free survival (DFS). Kaplan-Meier method and Cox proportional hazard model were applied, and the discrimination performance was measured by the concordance statistics (C-statistics). Results: A total of 8202 eligible patients were included in the analysis with a median follow up period of 51 months. 7415 (90.4%) patients had previously received radiation and 7038 (85.8%) patients had previously received chemotherapy. The median age of patients was 56 years. Distribution of stage I disease increased from 2% to 19.6% in AJCC 8th edition. 10-year overall survival (OS) for AJCC 8th stages I (74%), II (78%), III (55%) and IV (32%). Using Stage I as reference, the hazard ratio for stage II, III, and IV is 0.98 (95%CI: 0.87-1.09), 2.29 (95%CI: 2.04-2.57), and 5.88 (95%CI: 4.96-6.98). Similar results were noted for ten year disease free survival. The C-statistics measured overall discrimination for 8th edition is 0.68 and 0.63 for the 7th edition (P < 0.001). Conclusions: Based on this SEER analysis, the overall performance of discrimination improved from AJCC 7th to 8th edition; but in this study population, AJCC 8th edition does not distinguish stage I and II sufficiently as expected as it does for stages III and IV disease. Limitations of the SEER database include the surrogate for P16 status and under reported and incomplete data.

Chemokine receptors seem to impact on patient survival in head and neck squamous cell carcinoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 15527-15527
Author(s):  
M. H. Federico ◽  
C. M. Campofiorito ◽  
F. R. Mangone ◽  
S. Maistro ◽  
F. S. Pasini ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Chemokine Receptors ◽  
Disease Free Survival ◽  
Neck Squamous Cell Carcinoma ◽  
Ribonuclease Protection Assay ◽  
Curative Surgery ◽  
Tumor Spread

15527 Background and Methods: Chemokine receptors seem to be involved in tumor spread to lymph nodes and influence outcome in cancer patients (pts). Here, we have determined the mRNA expression of CCR7, CX3CR1 and CXCR1 chemokines, by means of Ribonuclease Protection Assay, in 60 fragments of primary tumor and matched adjacent mucosa of pts with head and neck squamous cells carcinoma (HNSCC) submitted to curative surgery. For Kaplan Meier survival curves, pts were categorized for each chemokine as positive or negative if above or equal/below median densitometric value of the entire tumor group. Results: In the whole study population, CCR7 status did not impact on overall survival (OS) (P=0.118, Log Rank) and on disease free survival (DFS) (P = 0.102), neither. When the subgroup of oral SCC was considered (n = 19), the CCR7 negative pts (n = 10) presented a longer DFS and OS (median DFS and OS not reached) as compared to CCR7 positive pts (n = 9) (mDFS: 4.9 months, P = 0.001 and mOS 10.47 months P = 0.003). In the HNSCC group as a whole, the CX3CR1 negative pts presented a trend toward longer OS (mOS 26.60 months in negative group, n = 25 vs 15.43 months in the positive group, n = 35, P = 0.073) and a longer DFS (mDFS not reached in CX3CR1 negative vs 9.20 months in positive pts, P = 0.041). In the oral SCC subgroup, CX3CR1 negative pts (n = 8) presented significantly better DFS (mDFS not reached) as compared to CX3CR1 positive pts (n = 11, mDFS 4.9 months, P = 0.004). OS was also superior for oral SCC CX3CR1 negative (mOS not reached) as compared to positive pts (mOS 10.47 months, P = 0.008). Taking into account larynx SCC, mDFS and mOS were not reached for CX3CR1 negative pts (n = 5) as compared to positive pts (n = 11, mDFS 8.57 months, P = 0.016; mOS 12.37 months, P = 0.041). In larynx subgroup, the other receptor associated to an advantage in terms of both DFS and OS was the negativity for CXCR1 (mDFS not reached for negative vs 8.47 months for positive pts, P = 0.006; mOS not reached for negative vs 8.47 months for positive pts, P = 0.025). Conclusions: Even if the mechanisms are not clear, our data suggest that low expression of CCR7, CX3CR1 and CXCR1 mRNA may be markers of better outcome in Head and Neck Squamous Cell Carcinoma. Further studies are warranted to confirm these results. No significant financial relationships to disclose.

Diagnostic evaluation of squamous cell carcinoma metastatic to cervical lymph nodes from an unknown head and neck primary site

2009 ◽  
Vol 119 (12) ◽  
pp. 2348-2354 ◽  
Author(s):  
Marco Cianchetti ◽  
Anthony A. Mancuso ◽  
Robert J. Amdur ◽  
John W. Werning ◽  
Jessica Kirwan ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Lymph Nodes ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Primary Site ◽  
Diagnostic Evaluation ◽  
Cervical Lymph Nodes

scholarly journals SWOG S0221: A Phase III Trial Comparing Chemotherapy Schedules in High-Risk Early-Stage Breast Cancer

2015 ◽  
Vol 33 (1) ◽  
pp. 58-64 ◽  
Author(s):  
George T. Budd ◽  
William E. Barlow ◽  
Halle C.F. Moore ◽  
Timothy J. Hobday ◽  
James A. Stewart ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Hormone Receptor ◽  
Early Stage ◽  
Disease Free Survival ◽  
Early Stage Breast Cancer ◽  
Phase Iii ◽  
Secondary Outcome ◽  
Original Design ◽  
Significant Difference

Purpose To determine the optimal dose and schedule of anthracycline and taxane administration as adjuvant therapy for early-stage breast cancer. Patients and Methods A 2 × 2 factorial design was used to test two hypotheses: (1) that a novel continuous schedule of doxorubicin-cyclophosphamide was superior to six cycles of doxorubicin-cyclophosphamide once every 2 weeks and (2) that paclitaxel once per week was superior to six cycles of paclitaxel once every 2 weeks in patients with node-positive or high-risk node-negative early-stage breast cancer. With 3,250 patients, a disease-free survival (DFS) hazard ratio of 0.82 for each randomization could be detected with 90% power with two-sided α = .05. Overall survival (OS) was a secondary outcome. Results Interim analyses crossed the futility boundaries for demonstrating superiority of both once-per-week regimens and once-every-2-weeks regimens. After a median follow-up of 6 years, a significant interaction developed between the two randomization factors (DFS P = .024; OS P = .010) in the 2,716 patients randomly assigned in the original design, which precluded interpretation of the two factors separately. Comparing all four arms showed a significant difference in OS (P = .040) but not in DFS (P = .11), with all treatments given once every 2 weeks associated with the highest OS. This difference in OS seemed confined to patients with hormone receptor–negative/human epidermal growth factor receptor 2 (HER2) –negative tumors (P = .067), with no differences seen with hormone receptor–positive/HER2-negative (P = .90) or HER2-positive tumors (P = .40). Conclusion Patients achieved a similar DFS with any of these regimens. Subset analysis suggests the hypothesis that once-every-2-weeks dosing may be best for patients with hormone receptor–negative/HER2-negative tumors.

scholarly journals PD-L1 expression predicts longer disease free survival in high risk head and neck cutaneous squamous cell carcinoma

Pathology ◽  
2017 ◽  
Vol 49 (5) ◽  
pp. 499-505 ◽  
Author(s):  
Edward Roper ◽  
Trina Lum ◽  
Carsten E. Palme ◽  
Bruce Ashford ◽  
Sydney Ch'ng ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Disease Free Survival ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Free Survival ◽  
Disease Free
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