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Objectives: To explore the effect of incorporating cetuximab into induction chemotherapy in locally advanced head and neck squamous cell carcinoma (HNSCC)., Materials and Methods: Retrospective comparative analysis of two consecutive prospective phase II trials was performed: trial 1 with nab-paclitaxel/cisplatin/5-FU and cetuximab (APF-C; n=30) and trial 2 with APF (n=30). Patients were scheduled to receive chemoradiation therapy (CRT) with cisplatin. T 2-4 classification oropharynx (OP)/larynx/hypopharynx SCC were included. Cumulative incidence of death of disease (CIDD), overall survival (OS), and cumulative incidence of relapse were compared between APF-C and APF., Results: No significant differences in patient or tumor characteristics were noted between the groups. Median follow-up of surviving patients was 52 (25-95) months. Relapse occurred in 5 (17%) patients treated with APF-C and in 2 (7%) treated with APF (p=0.37). In human papillomavirus (HPV)-related OPSCC (n=34), the CIDD at 52months was 3.4% with APF-C and 2.6% with APF and the two-year OSs were 94%. In HPV-unrelated HNSCC (n=25), the CIDD at 52months was 4.4% with APF-C and 3.3% with APF and two-year OSs were 83% and 92%, respectively. CIDD or OS did not differ when stratified by treatment group and HPV status (CIDD: p=0.80; OS: p=0.30)., Conclusion: This exploratory retrospective comparative analysis demonstrated no significant difference in CIDD, OS, or cumulative incidence of relapse between patients treated with APF-C or APF., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Adenosquamous carcinoma (AdSC) is considered a rare variant of squamous cell carcinoma (SCC) which is considered to be more clinically aggressive. Data is very limited with very little case matched data on outcomes in the literature. It is also unknown whether the quantity of the adenocarcinoma component affects outcomes. A retrospective case-control study with 23 cases of AdSC and 1137 SCC controls was conducted. Cases were matched by anatomic subsite, treatment, and, for oropharynx, by p16 status. The following variables were adjusted for in the analysis: T classification (T1/T2 vs. T3/T4), N classification (N0-N2a vs. N2b-N3), age, and smoking. The adenocarcinoma component was quantified by the number of high power fields containing glands as low, moderate, or high. AdSCs had a significantly greater risk of disease recurrence but largely, the differences were not statistically significant. The quantity of adenocarcinoma did not correlate with disease recurrence or survival. This case-control study on AdSC shows modestly more clinically aggressive behavior than conventional SCC, even while controlling for p16 status for oropharyngeal cases. Further, it suggests the current definition of AdSC, with no minimum requirement for gland formation, is clinically accurate.

Objectives: We previously reported the efficacy of nab-paclitaxel added to cisplatin, 5-FU, and cetuximab (APF-C) followed by concurrent high dose bolus cisplatin and radiation therapy (CRT) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). In this phase II trial, we determined the efficacy of APF (without cetuximab) followed by CRT in similar patients., Materials and Methods: Eligible patients had stage III-IV oropharynx (OP), larynx, or hypopharynx SCC and adequate organ function and performance status. T1 tumors were excluded. Patients were treated with three cycles of APF followed by CRT. Efficacy endpoints included two-year disease-specific survival (DSS), progression-free survival (PFS), overall survival (OS), and relapse rate., Results: Thirty patients were enrolled. Most patients were smokers (77%) with bulky T3/4 (73%) and N2/3 (83%) tumors. Analyses were stratified for human papilloma virus (HPV) status: HPV-related OPSCC (n=17; 57%) and HPV-unrelated HNSCC (n=13; 43%). With a minimum follow-up of 21months, relapse occurred in 1 (3%) patient. Two-year DSS was 94% in HPV-related OPSCC and 100% in HPV-unrelated HNSCC. Two-year PFS was 94% in HPV-related OPSCC and 100% in HPV-unrelated HNSCC. Two-year OS was 94% in HPV-related OPSCC and 92% in HPV-unrelated HNSCC. Causes of death were relapse (1), treatment-related mortality (1), and co-morbidity (1). Two patients with HPV-unrelated HNSCC treated with APF declined CRT and remained free of relapse at 36 and 28months of follow-up., Conclusion: This phase II trial demonstrated favorable two-year DSS, PFS, and OS and a low relapse rate in HPV-unrelated HNSCC and HPV-related OPSCC treated with APF followed by CRT., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objectives: To test the safety of the CDK4/6 inhibitor palbociclib with cetuximab in patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC)., Materials and Methods: A phase I trial using 3+3 design was performed to determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) of palbociclib with standard dose weekly cetuximab. Palbociclib was administered orally days 1-21 every 28days: dose level 1 (100mg/d) and 2 (125mg/d; approved monotherapy dose). Pharmacokinetic assessments were performed on cycle 2, day 15. Cyclin D1, p16(INK4a), and Rb protein expression were measured on pre-treatment tumor. Tumor response was assessed using RECIST1.1., Results: Nine patients (five p16(INK4a) negative; four positive) were enrolled across dose levels 1 (n=3) and 2 (n=6) and none experienced a DLT. A MTD of palbociclib was not reached. Myelosuppression was the most common adverse event. Six of nine patients had cetuximab-resistant and 4/9 had platin-resistant disease. Disease control (DC) occurred in 89%, including partial response (PR) in two (22%) and stable disease in six (67%) patients. PRs occurred in p16(INK4a) negative HNSCC. Five patients (56%) had measurable decreases in tumor target lesions. In cetuximab-resistant HNSCC, best tumor response was PR in 1 and DC in 5 and median TTP was 112days (range: 28-168). In platin-resistant HNSCC, best tumor response: PR in 1, DC in 3 and median TTP was 112days (range: 28-112). The Cmax and AUC0-24h appeared comparable in patients receiving 125 vs 100mg dose of palbociclib., Conclusion: This trial, the first to evaluate a CDK4/6 inhibitor in HNSCC, determined that palbociclib 125mg/day on days 1-21 every 28days with cetuximab was safe. Tumor responses were observed, even in cetuximab- or platin-resistant disease., Competing Interests: Conflict of Interest/Disclosures Disclosures: Research Support – Pfizer, (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Aim: To identify risk factors associated with esophageal cancer in Zambia and association between dietary intake and urinary 8-iso prostaglandin F2α (8-isoPGF2α)., Methods: We conducted a prospective, case control study at the University Teaching Hospital. Subjects included both individuals admitted to the hospital and those presenting for an outpatient upper endoscopy. Esophageal cancer cases were compared to age and sex-matched controls. Cases were defined as patients with biopsy proven esophageal cancer; controls were defined as subjects without endoscopic evidence of esophageal cancer. Clinical and dietary data were collected using a standard questionnaire, developed a priori. Blood was collected for human immunodeficiency virus (HIV) serology. Urine was collected, and 8-isoPGF2α was measured primarily by enzyme-linked immunosorbent assay and expressed as a ratio to creatinine., Results: Forty five controls (mean age 54.2 ± 15.3, 31 male) and 27 cases (mean age 54.6 ± 16.4, 17 males) were studied. Body mass index was lower in cases (median 16.8) than controls (median 23.2), P = 0.01. Histopathologically, 25/27 (93%) were squamous cell carcinoma and 2/27 (7%) adenocarcinoma. More cases smoked cigarettes (OR = 11.24, 95%CI: 1.37-92.4, P = 0.02) but alcohol consumption and HIV seropositivity did not differ significantly (P = 0.14 for both). Fruit, vegetables and fish consumption did not differ significantly between groups (P = 0.11, 0.12, and 0.10, respectively). Mean isoprostane level was significantly higher in cases (0.03 ng/mg creatinine) than controls (0.01 ng/mg creatinine) (OR = 2.35, 95%CI: 1.19-4.65, P = 0.014)., Conclusion: Smoking and isoprostane levels were significantly associated with esophageal cancer in Zambians, but diet, HIV status, and alcohol consumption were not.

We previously reported that nab-paclitaxel-based induction chemotherapy (IC) and concurrent chemoradiotherapy resulted in low relapse rates (13%) and excellent survival in head and neck squamous cell carcinoma (HNSCC). We compare the disease-specific survival (DSS) and overall survival (OS) between patients given nab-paclitaxel, cisplatin, and fluorouracil with cetuximab (APF-C) and historical controls given docetaxel, cisplatin, and fluorouracil with cetuximab (TPF-C). Patients with locally advanced HNSCC were treated with APF-C (n = 30) or TPF-C (n = 38). After 3 cycles of IC, patients were scheduled to receive cisplatin concurrent with definitive radiotherapy. T and N classification and smoking history were similar between the two groups and within p16-positive and p16-negative subsets. The median duration of follow-up for living patients in the APF-C group was 43.5 (range: 30-58) months versus 52 (range: 13-84) months for TPF-C. The 2-year DSS for patients treated with APF-C was 96.7% [95% Confidence Interval (CI): 85.2%, 99.8%] and with TPF-C was 77.6% (CI: 62.6%, 89.7%) (P = 0.0004). Disease progression that resulted in death was more frequent in the TPF-C group (39%) compared with the APF-C group (3%) when adjusted for competing risks of death from other causes (Gray's test, P = 0.0004). In p16 positive OPSCC, the 2-year DSS for APF-C was 100% and for TPF-C was 74.6% (CI: 47.4%, 94.6%) (P = 0.0019) and the 2-year OS for APF-C was 94.1% (CI: 65.0%, 99.2%) and for TPF-C was 74.6% (CI: 39.8%, 91.1%) (P = 0.013). In p16 negative HNSCC, the 2-year DSS for APF-C was 91.7% (CI: 67.6%, 99.6%) and for TPF-C was 82.6% (CI: 64.4%, 94.8%) (P = 0.092). A 2-year DSS and OS were significantly better with a nab-paclitaxel-based IC regimen (APF-C) compared to a docetaxel-based IC regimen (TPF-C) in p16-positive OPSCC., (© 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Computed tomography (CT), the standard method to assess tumor response to cetuximab in incurable squamous cell carcinoma of the head and neck (SCCHN), performs poorly as judged by the disparity between high disease control rate (46%) and short time to progression (TTP) (70 days). F-18 fluorodeoxyglucose positron emission tomography (FDG-PET)/CT is an alternative method to assess tumor response. The primary objective of this prospective trial was to evaluate the metabolic response of target lesions, assessed as the change in maximum standardized uptake value (SUV(max)) on FDG-PET/CT before and after 8 weeks (cycle 1) of cetuximab. Secondary objectives were to compare tumor response by CT (RECIST 1.0) and FDG-PET/CT (EORTC criteria) following cycle 1, and determine TTP with continued cetuximab administration in patients with disease control by CT after cycle 1 but stratified for disease control or progression by FDG-PET/CT. Among 27 patients, the mean percent change of SUV(max) of target lesions after cycle 1 was -21% (range: +72% to -81%); by FDG-PET/CT, partial response (PR)/stable disease (SD) occurred in 15 patients (56%) and progression in 12 (44%), whereas by CT, PR/SD occurred in 20 (74%) and progression in 7 (26%). FDG-PET/CT and CT assessments were discordant in 14 patients (P = 0.0029) and had low agreement (κ = 0.30; 95% confidence interval [CI]: 0.12, 0.48). With disease control by CT after cycle 1, median TTP was 166 days (CI: 86, 217) if the FDG-PET/CT showed disease control and 105 days (CI: 66, 159) if the FDG-PET/CT showed progression (P < 0.0001). Median TTP of the seven patients whose post cycle 1 CT showed progression compared to the 12 whose FDG-PET/CT showed progression were similar (53 [CI: 49, 56] vs. 61 [CI: 50, 105] days, respectively). FDG-PET/CT may be better than CT in assessing benefit of cetuximab in incurable SCCHN., (© 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Complete response (CR) at the primary tumor site as assessed by clinical examination following induction chemotherapy with PF (cisplatin and 5-fluorouracil [5-FU]) is a favorable predictive factor for overall survival and disease control in patients with locally advanced squamous cell carcinoma of the head and neck. In most series, the rate of CR at the primary site after induction PF was 20% to 30%. This study evaluated the efficacy and feasibility of induction nab-paclitaxel and cetuximab given with PF (ACPF) followed by definitive chemoradiation (CRT) in a phase 2 trial., Methods: Patients with squamous cell carcinoma of the head and neck were treated with ACPF (nab-paclitaxel 100 mg/m(2) /week; cetuximab 250 mg/m(2) /week; cisplatin 75 mg/m(2) on day 1; 5-FU 750 mg/m(2) /day on days 1 through 3) every 21 days for 3 cycles followed by CRT (cisplatin 100 mg/m(2) on days 1, 22, and 43 of radiation therapy [RT]). CR at the primary tumor site after 2 cycles of ACPF was the primary endpoint., Results: Thirty patients were enrolled, of which 22 (73%) had large (T3/T4) primary tumors. The CR rate at the primary tumor site after 2 cycles of ACPF was 53% and the overall response rate was 100%. Twenty-nine (96%) patients completed 3 cycles of ACPF, 26 (90%) completed definitive RT per protocol, and 22 of the 27 evaluable patients (81%) received > 2 of the 3 planned doses of cisplatin with RT. The estimated 2-year overall and progression-free survival rates were 84% and 65%, respectively., Conclusions: Induction ACPF resulted in a high CR rate (53%) at the primary tumor site even in large tumors and did not adversely affect delivery of definitive CRT. Further investigation of ACPF is warranted., (Copyright © 2012 American Cancer Society.)

Objective: Whether or not cisplatin and cetuximab are similarly effective in improving outcomes when added to radiation therapy (RT) in squamous cell carcinoma of the head and neck is unknown., Methods: Retrospective analysis was performed of patients treated with definitive RT and cisplatin (n = 18) or cetuximab (n = 29)., Results: T and N classifications, stage, human papillomavirus status and smoking history were balanced in the two groups; however, patients in the cisplatin group were younger and had a better performance status. Delivery of RT was similar between the two groups. Median follow-up was 23 (4-64) months. Disease-specific survival (DSS) at 3 years was 83% in the cisplatin group and 31% in the cetuximab group. Recurrent disease was more common in the cetuximab group compared with the cisplatin group (17 vs. 4 patients). Propensity score analysis to adjust for differences in patient characteristics which influenced treatment selection showed that DSS was indeed longer with cisplatin than with cetuximab (DSS hazard ratio 0.15, confidence interval 0.033, 0.66; p = 0.012)., Conclusions: DSS was superior in the patients given cisplatin with definitive RT compared to cetuximab with definitive RT due to a lower risk of recurrent disease in the cisplatin group. These observations could not be explained by differences between the two groups in the patient and tumor characteristics or in treatment delivery., (© 2013 S. Karger AG, Basel.)

Background: Increased tumor size is a known risk for poor outcomes in patients with stage I and II non-small cell lung cancer (NSCLC), who are treated with surgery or radiotherapy. However, there is limited information regarding the impact of tumor size on the outcomes of patients with mediastinal lymph node involvement. We conducted a Surveillance, Epidemiology, and End Results (SEER) database analysis to evaluate the prognostic significance of tumor size in patients with unresected stage III NSCLC., Methods: The SEER registry was queried for patients with unresected NSCLC stage III and no malignant pleural effusion, aged 21 years or older, and diagnosed between 1998 and 2003. Tumor size was defined as S1 (0.1-3 cm), S2 (3.1-5 cm), S3 (5.1-7 cm), and S4 (7.1-20 cm). Demographic variables included age, sex, race and histology. Overall survival (OS) and disease-specific survival (DSS) were estimated by the Kaplan-Meier method, and the Cox proportional hazard model was used to evaluate whether tumor size remained an independent risk factor in multivariable analysis., Results: A total of 12,315 patients met the eligibility criteria. Median age at diagnosis was 70 years and most patients were men (58.7%) and white (81.3%). Tumor size was an independent predictor for both OS (p < 0.0001) and DSS (p < 0.001) in all subgroups of patients., Conclusion: Tumor size is an independent predictor for OS and DSS in patients with unresected stage III NSCLC, and should be considered in the stratification of patients treated in this setting after validation of this finding in additional studies.

Background: Current literature reports widely different rates of distant metastasis at presentation for squamous cell carcinoma of the head and neck (SCCHN). We used the Surveillance Epidemiology and End Results (SEER) database to determine the rate of and risk factors for distant metastasis., Methods: We identified patients with SCCHN diagnosed between 1988 and 2003. The rate of distant metastasis was determined and then stratified by tumor site, size, and nodal status. To evaluate the contribution of each individual factor, both univariate and multivariate analyses were performed., Results: Among 73,247 patients identified, 2066 patients (2.82%, 95% confidence interval [CI] 2.70-2.94%) had distant metastasis. Independent risk factors for distant metastasis included primary site, nodal status, tumor size, age, and race., Conclusions: In SCCHN, there is a relationship between the risk of distant metastasis and tumor site, size, and nodal status. This information can be used to guide the evaluation and treatment of SCCHN., (Copyright © 2010 Wiley Periodicals, Inc.)