Upfront chemotherapy and accelerated radiotherapy with EGFR inhibition for locally advanced inoperable head and neck cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6040-6040
Author(s):  
C. Mercke ◽  
G. Wickart-Johansson ◽  
H. Sjödin ◽  
G. Adell ◽  
J. Nyman ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cavity ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Locally Advanced ◽  
Stage Iv ◽  
Resected Specimen ◽  
Stage Iv Disease

6040 Background: Concomitant chemoradiotherapy (CT/RT) is the standard treatment for locally advanced head and neck squamous cell carcinoma. However, late toxicity is substantial.This phase II trial explores the feasibility and efficacy of combining neoadjuvant TPF and accelerated RT where the concomitant cytostatic component is replaced with cetuximab (E), a chimeric IgG1 mAb against EGFR. Methods: Patients (pts) had previously untreated stage III/IV M0,WHO 0–1, unresectable squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx and were scheduled for 2 cycles of TPF (docetaxel 75 mg/m2 and cisplatin 75 mg/m2 day 1 and 5-FU 1,000 mg/m2 96 hours CI) every 3 weeks followed by RT (68 Gy/4.5 weeks) with E given one week before (400 mg/m2) and weekly during RT (250 mg/m2). A brachytherapy boost of 8 Gy was given to pts with oral cavity or oropharyngeal tumours. Neck dissection was planned for pts with N2–3 and complete response (CR) at the primary tumour. Tumour response was evaluated according to RECIST with CT, MRI or PET/CT after CT and at 6 weeks follow up. Toxicity (CTC 3.0) and quality of life (EORTC QLQ 30) was registered during and after treatment. Results: From 070401 to 081115 68 pts were enrolled, 56 had stage IV disease (T4, n = 14, N3, n = 9). Median age 57, 60 males, 3 oral cavity, 44 oropharynx, 10 larynx, and 11 hypopharynx. 30 pts were followed beyond 6 weeks and evaluated for response and early toxicity: stage IV disease 24 (T4, n = 6, N3, n = 3), median age 60, 25 males, 18 oropharynx, 5 larynx, and 7 hypopharynx. Remissions after TPF/after RT: CR 1/10, PR 15/18, SD 14/1, and PD 1. TPF as prescribed: 28/30 (pat refusal 1, renal insuff 1, dose reduction 0/28); E as prescribed: 22/30 (dermatitis 4, hypersensitivity 3, liver tox 1). Vital tumour in resected specimen 0/13. Alive at follow-up 29/30 (1 local failure). Conclusions: TPF followed by RT concomitant with E is feasible with manageable toxicities. Dermatitis in the irradiated neck, at least with the present accelerated fractionation, is troublesome to some patients but does not interrupt treatment and heals rapidly. To dispose of feeding tubes after disappearance of acute mucosal reactions has not been a problem. Early survival results are promising. Toxicity and survival results will be updated. [Table: see text]

scholarly journals Photodynamic Therapy as an Alternative Therapeutic Tool in Functionally Inoperable Oral and Oropharyngeal Carcinoma: A Single Tertiary Center Retrospective Cohort Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Arnaud Lambert ◽  
Lotte Nees ◽  
Sandra Nuyts ◽  
Paul Clement ◽  
Jeroen Meulemans ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Photodynamic Therapy ◽  
Oral Cavity ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Standard Treatment ◽  
Treated Area ◽  
Free Interval

Background: Head and neck cancer is typically treated with surgery, radiotherapy, chemoradiation, or a combination of these treatments. This study aims to retrospectively analyse oncological outcomes, adverse events and toxicity of treatment with temoporfin-mediated photodynamic therapy at a single tertiary referral center. More specifically, in a selected group of patients with otherwise (functionally) inoperable oral or oropharyngeal head and neck squamous cell carcinoma.Methods: Twenty-six consecutive patients who received photodynamic therapy for oral or oropharyngeal squamous cell carcinoma from January 2002 until July 2019 at the University Hospitals Leuven were included. These were (1) patients with an accessible recurrent or new primary tumor in an extensively treated area of the head and neck, not suitable for standard treatment, or (2) patients that were judged medically unfit to undergo standard treatment modalities.Results: Complete tumor response immediately after PDT was obtained in 76.9% of cases. During follow-up, a proportion of CR patients did recur, to reach recurrence-free rates at six months, one year and two years of 60.6%, 48.5% and 32.3%. Local control at the PDT treated area was 42.3% with a median recurrence free interval time of 9 months. Recurrence-free interval was statistically more favorable for oropharyngeal squamous cell carcinoma (with or without oral cavity extension) in comparison to oral cavity squamous cell carcinoma alone (p < 0.001). During a median follow-up period of 27 months, we report new tumor activity in 80.8% of patients. Median overall and disease-specific survival time was 31 and 34 months, respectively. Most reported adverse events were pain after treatment and facial edema. At the end of follow-up, swallowing and upper airway functionality were preserved in 76.9 and 95.7% of patients, respectively.Conclusion: Photodynamic therapy is a valuable treatment option in highly selected patients with oral and/or oropharyngeal (functionally) inoperable head and neck squamous cell carcinoma. Treatment with this alternative modality can induce durable local control in an important fraction of treated patients, with an acceptable toxicity profile.

scholarly journals Predictors of Survival After Head and Neck Squamous Cell Carcinoma in South America: The InterCHANGE Study

2020 ◽  
pp. 486-499 ◽  
Author(s):  
Renata Abrahão ◽  
Sandra Perdomo ◽  
Luis Felipe Ribeiro Pinto ◽  
Flávia Nascimento de Carvalho ◽  
Fernando Luis Dias ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
South America ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Cox Regression ◽  
Survival Rates ◽  
Stage Iv ◽  
Neck Squamous Cell Carcinoma ◽  
Stage Iv Disease

PURPOSE Head and neck squamous cell carcinoma (HNSCC) incidence is high in South America, where recent data on survival are sparse. We investigated the main predictors of HNSCC survival in Brazil, Argentina, Uruguay, and Colombia. METHODS Sociodemographic and lifestyle information was obtained from standardized interviews, and clinicopathologic data were extracted from medical records and pathologic reports. The Kaplan-Meier method and Cox regression were used for statistical analyses. RESULTS Of 1,463 patients, 378 had a larynx cancer (LC), 78 hypopharynx cancer (HC), 599 oral cavity cancer (OC), and 408 oropharynx cancer (OPC). Most patients (55.5%) were diagnosed with stage IV disease, ranging from 47.6% for LC to 70.8% for OPC. Three-year survival rates were 56.0% for LC, 54.7% for OC, 48.0% for OPC, and 37.8% for HC. In multivariable models, patients with stage IV disease had approximately 7.6 (LC/HC), 11.7 (OC), and 3.5 (OPC) times higher mortality than patients with stage I disease. Current and former drinkers with LC or HC had approximately 2 times higher mortality than never-drinkers. In addition, older age at diagnosis was independently associated with worse survival for all sites. In a subset analysis of 198 patients with OPC with available human papillomavirus (HPV) type 16 data, those with HPV-unrelated OPC had a significantly worse 3-year survival compared with those with HPV-related OPC (44.6% v 75.6%, respectively), corresponding to a 3.4 times higher mortality. CONCLUSION Late stage at diagnosis was the strongest predictor of lower HNSCC survival. Early cancer detection and reduction of harmful alcohol use are fundamental to decrease the high burden of HNSCC in South America.

EGFRv3 and PTEN as prognostic markers in head and neck squamous cell carcinoma patients treated with cetuximab.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e17032-e17032
Author(s):  
Alexandre Andre Balieiro Anastacio da Costa ◽  
Adriana Regina G. Ribeiro ◽  
Andrea Paiva Guimaraes ◽  
Ludmilla Thome Chinen ◽  
Clovis Pinto ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Objective Response ◽  
Locally Advanced ◽  
Population Characteristics ◽  
Neck Squamous Cell Carcinoma ◽  
Phase Iii

e17032 Background: Cetuximab (CTx) is used in treatment of locally advanced (LAD) head and neck squamous cell carcinoma (HNSCC) in combination with radiotherapy (RT) or in metastatic disease (MD). There is no comparison between CTx plus RT and cisplatin plus RT. Patients treated with CTx in daily clinical practice are frequently different from the selected population treated in clinical trials. There are no biomarkers for efficacy of CTx in HNSCC. EGFR variant 3 mutation (EGFRv3), an extracellular domain mutation of EGFR, has been reported in different frequencies in HNSCC in the last years and its association with prognosis and CTx efficacy is still unknown. Methods: Retrospective review of data from patients with HNSCC treated with CTx at a single institution from 2007 to 2010. We evaluated CTx efficacy and expression of EGFRv3, EGFR, PTEN, CD44 and CD44v6 and their impact in objective response rate (ORR), progression free survival (PFS) and overall survival (OS). Biomarkers were analyzed by immunohistochemistry in tissue microarray. Results: For a median follow-up time of 13 months, 61 patients with LAD treated with RT plus CTx had a median OS of 22.7 months, and a median PFS of 8.0 months. Age adjusted Charlson Comorbidity Index (AA-CCI) and ECOG performance status were the most important predictors of poor prognosis in this population. For a median follow-up time of 10.9 months, 44 patients with MD had a median OS of 13.0 months and a median PFS of 7.0 months, for an ORR of 53.7%. EGFRv3 was expressed in 27.1% of tumor samples and was not associated with any clinical outcome. EGFR positivity was associated to higher ORR in LAD and PTEN negativity was associated with shorter OS in the MD setting. Conclusions: In a non selected population with LAD treatment results with CTx in combination with radiotherapy were worse than expected by the phase III study, median OS 22.7 months vs 49.0 months. This difference may be attributed to different population characteristics with higher ECOG and AA-CCI in our study and warrants an adequate proof of efficacy of CTx in this population. EGFRv3 is present in HNSCC but does not impact prognosis. PTEN and EGFR expression emerged as potential biomarkers in HNSCC patients treated with CTx.

Incidence of hypothyroidism in head and neck squamous cell carcinoma patients receiving radiotherapy with and without immune checkpoint inhibitors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18551-e18551
Author(s):  
Jennifer Leddon ◽  
Martina Chirra ◽  
Arushi Agrawal ◽  
Logan Roof ◽  
Danny Trotier ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Risk Factor ◽  
Oral Cavity ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Primary Tumor ◽  
Thyroid Dysfunction ◽  
Neck Squamous Cell Carcinoma

e18551 Background: Treatment for locally advanced head and neck squamous cell carcinoma (HNSCC) involves a combination of surgery, chemotherapy, and radiotherapy (RT). RT for HNSCC is a known risk factor for the development of hypothyroidism. Recently, anti-PD1 therapies have been approved for recurrent and metastatic HNSCC and are moving to the forefront of HNSCC care. Similarly, thyroid dysfunction is a common immune-related adverse event following anti-PD1 therapy. Whether the addition of anti-PD1 to RT increases the likelihood of developing hypothyroidism remains unknown. Methods: The rate of hypothyroidism in HNSCC patients receiving RT (+/- chemotherapy and surgery) was compared to HNSCC patients receiving RT + anti-PD1 therapy either concurrently or after RT. Exclusion criteria were preexisting thyroid dysfunction, RT dose < 45 Gy and patients with incomplete treatment records. We defined clinical hypothyroidism as an elevation of TSH with low T3, T4 or elevation of TSH with symptoms requiring levothyroxine initiation. Hypothyroidism incidence was compared using Fisher’s exact test. Results: 153 patients were evaluated. In the RT group (N = 103), patients received RT +/- surgery or chemotherapy. 82/103 (80%) were male, median age was 57 and primary tumor groups included oropharynx 62/103 (60%), larynx 29/103 (28%), oral cavity 9/103 (9%) and other 3/103 (3%). In the RT + anti-PD1 group (N = 50), 36/50 (72%) were males, median age was 57 and primary tumor groups included oral cavity 19/50 (38%), oropharynx 17/50 (34%), larynx 8/50 (16%), and other 6/50 (12%). In the RT group, median follow up after RT was 801 days. In the RT+ anti-PD1 group, median follow up was 595 days from RT and 388 days from anti-PD1. The rate of hypothyroidism was significantly higher in the RT group 22.3% (23/103) versus 6% (3/50)after anti-PD1 therapy (p = 0.011). Multinomial logistical regression found no significant difference in hypothyroidism based on age, sex, or BMI. Larynx as primary tumor location was an independent risk factor for development of hypothyroidism (OR 4.74, p = 0.002). Conclusions: The addition of anti-PD1 therapy to standard HNSCC treatments does not significantly increase the risk of developing hypothyroidism. In fact, this study finds a lower incidence of hypothyroidism in HNSCC patient receiving RT + PD1 therapy which may be due to shorter duration of follow up and lower proportion of laryngeal cancer patients who are at relatively higher risk for surgical hypothyroidism.

Paclitaxel and Carboplatin in Neo-Adjuvant and Concomitant Chemoradiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma

2002 ◽  
Vol 88 (6) ◽  
pp. 489-494 ◽  
Author(s):  
Gianni Fornari ◽  
Elisa Artusio ◽  
Lorenza Mairone ◽  
Mario Airoldi ◽  
Guido Bongioannini ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Locally Advanced ◽  
Neck Squamous Cell Carcinoma ◽  
Node Involvement ◽  
Ecog Ps ◽  
Local Regional Control

Aim and background To evaluate feasibility of neoadjuvant chemotherapy (NA-CT) followed by CT + radiotherapy (RT) in locally advanced or unresectable head and neck squamous cell carcinoma (HNSCC). Methods 22 HNSCC patients were enrolled (18 males, 4 females; median age, 59.5 years; median ECOG PS, 1). Sites of disease: oral cavity, 18.2%; oropharynx, 40.9%; hypopharynx, 18.2%; larynx, 4.6%, multiple sites, 18.2%. T (tumor) category: T2, 13.6%; T3, 31.8%;T4, 54.5%. N (nodes) category: N0, 9.1%; N1, 18.1%; N2, 40.9%; N3, 31.8%. Stage: III, 4.6%; IVA, 63.6%; IVB, 31.8%. Induction carboplatin (AUC = 6) and paclitaxel (200 mg/m2) × 3 cycles (q21 days) were given. Responders received definitive radiotherapy with concurrent carboplatin (35 mg/m2/day from days 1 to 5 in weeks 1, 3, 5 and 7) and paclitaxel (50 mg/m2 on days 10, 24 and 38). Patients with node involvement were suggested to undergo postradiotherapy neck dissection. Results NA-CT. 97% of planned chemotherapy cycles were administered. Prevalent toxicity was hematologic: 50% G4 neutropenia and 31.8% G3, one neutropenic fever. All patients had alopecia. Complete responses in T and N were 4 (18.2%) and 3 (15%), respectively. Partial responses were 13 (59%) and 9 (45%). There was 1 progressive disease. CT + RT. 79.9% of planned cycles of CT were administered. In 19 patients (86.4%) more than 50% of planned cycles of CT were completed. Median dose of RT was 70.2 Gy on T/N+ and 54 Gy on N0. Limiting toxicity was mucositis in 77.3%, followed by neutropenia (59.1% G3–G4). Median weight loss was 4.9%. 18.2% of patients required hospitalization. Complete responses in T and N were 15 (68.1%) and 8 (40%), respectively. Partial responses were 5 (22.7%) and 7 (35%). Conclusions The preliminary results of this study are encouraging, despite the toxicity. Adequate follow-up is required to evaluate efficacy in terms of local-regional control and overall survival.

scholarly journals Outcomes in Squamous Cell Carcinoma with Advanced Neck Disease

2007 ◽  
Vol 89 (7) ◽  
pp. 703-708 ◽  
Author(s):  
James A Keir ◽  
Olivia JH Whiteside ◽  
Stuart C Winter ◽  
Sushir Maitra ◽  
Rogan C Corbridge ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Postoperative Radiotherapy ◽  
Stage Iv ◽  
Surgical Excision ◽  
Kaplan Meier ◽  
Neck Disease ◽  
Stage Iv Disease

INTRODUCTION Treatment of advanced neck disease (N2c/N3) in head and neck squamous cell carcinoma is contentious. The aim of this study was to review the survival outcome following surgical excision of neck disease and the complications of this surgery. PATIENTS AND METHODS A retrospective review of the case notes of 39 patients treated at the Oxford Radcliffe Infirmary Head and Neck Unit with squamous cell carcinoma and advanced neck metastases confirmed as either pN2c or pN3 on histological examination was performed. Patients were treated with surgery and, in some cases, with adjunctive postoperative radiotherapy at the centre between August 1996 and November 2004. The study sought to establish the demographics, UICC staging/pathology, method of treatment, complications, recurrence and survival. Kaplan-Meier curves were used for statistical analysis of survival. Comparisons were then made between the cohort and historical control groups. RESULTS All patients were UICC stage IV disease. The 2- and 5-year overall survival in patients with resectable disease was 63% and 52%, respectively. DISCUSSION Patients with advanced neck disease have traditionally been thought to have terrible prognosis and, therefore, treatment is controversial. In treating advanced head and neck cancer, there has been a recent trend away from surgery towards chemotherapy and/or radiotherapy. CONCLUSIONS Comparing this study group to historical controls that include chemotherapy and/or radiotherapy, the outcomes appear favourable. The use of a combination of radiotherapy and surgery is advocated; it is suggested that advanced neck disease can have an acceptable prognosis and morbidity and that local disease control may be achieved.

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