Advanced Squamous Cell Head Research Articles

Differences and Similarities in the Pattern of Early Metabolic and Morphologic Response after Induction Chemo-Immunotherapy versus Induction Chemotherapy Alone in Locally Advanced Squamous Cell Head and Neck Cancer.

Simple SummaryThere are differences and similarities when assessing the short-term therapeutic response of chemotherapy and chemotherapy plus immunotherapy using imaging techniques, which may be necessary to make treatment decisions in malignant head and neck tumors. After both chemo- and immunochemotherapy, remission becomes measurable in cross-sectional and metabolic diagnostics after only one cycle of therapy, with 18FDG-PET/CT predicting complete remission of tumor cells in a representative biopsy better than MRI/CT examination in both therapeutic modalities. While complete tumor remission is highly likely (88%) after immunochemotherapy in tumors with low residual activity (≤40% of initial SUV), this is less common after chemotherapy alone (65%). In metabolic nonresponse with more than 80% residual activity, the probability of complete remission nevertheless is low after chemotherapy alone (6%). After immunochemotherapy, these false nonresponders are common (35%), requiring additional diagnostics by deep biopsy. Cases of pseudoprogression with an increase of SUVmax of more than 125% of the baseline were not observed.Background: In head and neck cancer patients, parameters of metabolic and morphologic response of the tumor to single-cycle induction chemotherapy (IC) with docetaxel, cis- or carboplatin are used to decide the further course of treatment. This study investigated the effect of adding a double immune checkpoint blockade (DICB) of tremelimumab and durvalumab to IC on imaging parameters and their significance with regard to tumor cell remission. Methods: Response variables of 53 patients treated with IC+DICB (ICIT) were compared with those of 104 who received IC alone. Three weeks after one cycle, pathologic and, in some cases, clinical and endoscopic primary tumor responses were evaluated and correlated with a change in 18F-FDG PET and CT/MRI-based maximum-standardized uptake values (SUVmax) before (SUVmaxpre), after treatment (SUVmaxpost) and residually (resSUVmax in % of SUVmaxpre), and in maximum tumor diameter (Dmax) before (Dmaxpre) and after treatment (Dmaxpost) and residually (resD). Results: Reduction of SUVmax and Dmax occurred in both groups; values were SUVmaxpre: 14.4, SUVmaxpost: 6.6, Dmaxpre: 30 mm and Dmaxpost: 23 mm for ICIT versus SUVmaxpre: 16.5, SUVmaxpost: 6.4, Dmaxpre: 21 mm, and Dmaxpost: 16 mm for IC alone (all p < 0.05). ResSUVmax was the best predictor of complete response (IC: AUC: 0.77; ICIT: AUC: 0.76). Metabolic responders with resSUVmax ≤ 40% tended to have a higher rate of CR to ICIT (88%; n = 15/17) than to IC (65%; n = 30/46; p = 0.11). Of the metabolic nonresponders (resSUVmax > 80%), 33% (n = 5/15) achieved a clinical CR to ICIT versus 6% (n = 1/15) to IC (p = 0.01). Conclusions: ICIT and IC quickly induce a response and 18F-FDG PET is the more accurate modality for identifying complete remission. The rate of discrepant response, i.e., pCR with metabolic nonresponse after ICIT was >30%.

Dual time point imaging in locally advanced head and neck cancer to assess residual nodal disease after chemoradiotherapy

BackgroundFDG-PET/CT has a high negative predictive value to detect residual nodal disease in patients with locally advanced squamous cell head and neck cancer after completing concurrent chemoradiotherapy (CCRT). However, the positive predictive value remains suboptimal due to inflammation after radiotherapy, generating unnecessary further investigations and possibly even surgery. We report the results of a preplanned secondary end point of the ECLYPS study regarding the potential advantages of dual time point FDG-PET/CT imaging (DTPI) in this setting. Standardized dedicated head and neck FDG-PET/CT images were obtained 12 weeks after CCRT at 60 and 120 min after tracer administration. We performed a semiquantitative assessment of lymph nodes, and the retention index (RI) was explored to optimize diagnostic performance. The reference standard was histology, negative FDG-PET/CT at 1 year, or > 2 years of clinical follow-up. The time-dependent area under the receiver operator characteristics (AUROC) curves was calculated.ResultsIn total, 102 subjects were eligible for analysis. SUV values increased in malignant nodes (median SUV1 = 2.6 vs. SUV2 = 2.7; P = 0.04) but not in benign nodes (median SUV1 = 1.8 vs. SUV2 = 1.7; P = 0.28). In benign nodes, RI was negative although highly variable (median RI = − 2.6; IQR 21.2), while in malignant nodes RI was positive (median RI = 12.3; IQR 37.2) and significantly higher (P = 0.018) compared to benign nodes. A combined threshold (SUV1 ≥ 2.2 + RI ≥ 3%) significantly reduced the amount of false-positive cases by 53% (P = 0.02) resulting in an increased specificity (90.8% vs. 80.5%) and PPV (52.9% vs. 37.0%), while sensitivity (60.0% vs. 66.7%) and NPV remained comparably high (92.9% vs. 93.3%). However, AUROC, as overall measure of benefit in diagnostic accuracy, did not significantly improve (P = 0.62). In HPV-related disease (n = 32), there was no significant difference between SUV1, SUV2, and RI in malignant and benign nodes, yet this subgroup was small.ConclusionsDTPI did not improve the overall diagnostic accuracy of FDG-PET/CT to detect residual disease 12 weeks after chemoradiation. Due to differences in tracer kinetics between malignant and benign nodes, DTPI improved the specificity, but at the expense of a loss in sensitivity, albeit minimal. Since false negatives at the 12 weeks PET/CT are mainly due to minimal residual disease, DTPI is not able to significantly improve sensitivity, but repeat scanning at a later time (e.g. after 12 months) could possibly solve this problem. Further study is required in HPV-associated disease.

A phase 1, first-in-human, drug dose-escalation study of RM-1995 photoimmunotherapy, as monotherapy or combined with pembrolizumab, in patients with advanced cutaneous squamous cell carcinoma or with head and neck squamous cell carcinoma.

TPS6103 Background: RM-1995 comprises an antibody against CD25, conjugated with a light-activatable dye (IRDye 700DX), which can subsequently be activated by illumination with 690 nm non-thermal red light for precise, targeted cell killing. Administration of the antibody-dye conjugate followed by local illumination results in target cell membrane disruption, while limiting damage to surrounding tissue. CD25 (lL-2Rα) is highly expressed by regulatory T cells (Tregs), thereby providing an opportunity to specifically target intratumoral Tregs for depletion via photoimmunotherapy. Tregs are critical in promoting immune homeostasis; however, in the context of solid tumors, Treg-mediated suppression detrimentally constrains anticancer T-cell responses, and a low ratio of CD8+ T cells:Tregs in the tumor is negatively correlated with clinical outcomes. Preclinical data suggest that RM-1995 photoimmunotherapy treatment alleviates local Treg-mediated restraint within the tumor microenvironment. Anticancer responses were further improved when combined with anti-PD-1 checkpoint inhibition. Methods: A phase 1 first-in-human dose-escalation study of RM-1995 photoimmunotherapy as monotherapy, or in combination with pembrolizumab, in patients with advanced cutaneous squamous cell carcinoma (cuSCC) and head and neck squamous cell carcinoma (HNSCC) is now enrolling (NCT05220748). The phase 1a portion will evaluate safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of single-agent RM-1995 photoimmunotherapy and determine the maximum tolerated dose or maximum administered dose of RM-1995 with a fixed light dose for tumor illumination. The phase 1b portion will include combination therapy with pembrolizumab. Enrolled patients will receive RM-1995 IV, followed 24±4 hours later by local tumor illumination. Pembrolizumab (200 mg) will be administered 5–7 days prior to RM-1995 infusion, then again 3 weeks later. Patients may be eligible to receive repeated photoimmunotherapy cycles for up to 12 months. Primary outcomes include safety and tolerability, and dose finding. The study will include cuSCC or HNSCC patients with locally advanced or locoregional disease with or without metastases that has recurred or progressed on or after platinum-based chemotherapy, and who are not eligible for further locoregional treatment. Other criteria include ECOG 0–2 and having ≥1 tumor accessible for illumination. Key exclusion criteria are: tumor sites located in sensitive or vital anatomic structures or invading a major blood vessel (unless treated to prevent hemorrhage); and other clinically significant or uncontrolled disease processes. An estimated 18 patients will be enrolled into each portion of the study. Clinical trial information: NCT05220748.

Radiotherapy plus cetuximab for locally advanced squamous cell head and neck cancer in patients with cisplatin-ineligible renal dysfunction: A retrospective study.

Clinical trials have not fully demonstrated the efficacy and safety of radiotherapy plus cetuximab for locally advanced squamous cell head and neck cancer (LA-SCCHN) in patients with cisplatin-ineligible renal dysfunction. Patients who received radiotherapy plus cetuximab for LA-SCCHN at Chiba University Hospital (Chiba, Japan) between July 2013 and October 2018 were retrospectively reviewed. Background characteristics and locoregional control and overall survival rates were compared between patients with and without renal dysfunction. Survival was examined using Kaplan-Meier analysis and an adjusted Cox proportional hazards model. Kaplan-Meier analysis demonstrated that overall survival was shorter in patients with creatinine clearance of <45 ml/min (P=0.041; log-rank test). However, there was no difference in the locoregional control rate (P=0.477; log-rank test). Adjusted Cox analysis revealed that the risk of death was increased by 2.52-fold (hazard ratio, 2.52; 95% confidence interval, 1.01-6.30; P=0.048) if creatinine clearance was <45 ml/min. Moderate to severe renal dysfunction did not affect the locoregional control rate in patients with LA-SCCHN treated with radiotherapy plus cetuximab but was an adverse prognostic factor.

PET/CT Surveillance in Advanced Squamous Cell Head and Neck Cancer (HNSCC) in Aberdeen 2016–2018

PET/CT Surveillance in Advanced Squamous Cell Head and Neck Cancer (HNSCC) in Aberdeen 2016–2018

Effects of GC4419 (avasopasem manganese) on chronic kidney disease in head and neck cancer patients treated with radiation and cisplatin.

12071 Background: Nephrotoxicity is a major complication of platinum-based chemotherapy and ranges in incidence from 31-68%. The effects of platinum-based chemotherapeutics on long-term renal outcomes (chronic kidney disease, CKD) profoundly affect morbidity and mortality. Concurrent chemoradiotherapy (CRT) including cisplatin is standard for locally advanced squamous cell head and neck cancer (HNC) but is accompanied by the risk of CKD. In a randomized, multi-center, placebo-controlled Phase 2b trial ( NCT02508389 ) of GC4419 (avasopasem manganese) in HNC patients receiving CRT, avasopasem reduced the duration, incidence, and severity of severe oral mucositis (Anderson et al, JCO 2019). Avasopasem did not appear to alter the safety profile of CRT in that trial, including incidence of adverse events of kidney injury or azotemia. Methods: Pre- and post-treatment markers of kidney function including blood urea nitrogen (BUN), serum creatinine (sCr), and estimated glomerular filtration rate (eGFR) were retrospectively evaluated for a subset of 52 of the trial patients who received 3 cycles x 100 mg/m2 cisplatin plus placebo or 30 or 90 mg of avasopasem intravenously prior to RT, and 7 comparator patients who received the same CRT outside the study. Kidney function was evaluated between 3- and 24-months post-completion of cisplatin-radiation therapy by two-way analysis of variance (ANOVA) as defined by the Kidney Disease Improving Global Outcomes (KDIGO) CKD staging. Results: Baseline patient characteristics were skewed towards a male population but were balanced across all treatment arms with regards to baseline kidney function (comparator + placebo, n = 19; 30 mg GC4419, n = 18; 90 mg GC4419, n = 15). Treatment with 90 mg GC4419 demonstrated normal BUN values (10-20 mg/dL) at 3, 6, and 18 months and normal sCr values (0.6-1.2 mg/dL) between 3 and 24 months as compared to the placebo arm + comparator group, which exhibited statistically elevated BUN and sCr (p &lt; 0.05). Treatment with 90 mg GC4419 also demonstrated significantly higher eGFR between 3 and 24 months post-chemoradiation (p &lt; 0.05) compared to the placebo arm + comparator group. 90 mg GC4419 treatment significantly reduced the incidence of CKD compared to the placebo arm and comparator group, as determined by fold change in sCr values and eGFR measurements &lt; 60 mL/min (stage G3a/b, G4, or G5 CKD). Conclusions: Avasopasem has the potential to reduce the incidence and severity of CKD in patients receiving cisplatin therapy. Clinical trial information: NCT02508389 .

Definitive Radiotherapy for Elderly Patients with Locally Advanced Squamous Cell Head and Neck Cancer (LAHNSCC): A Single-Institution Experience

Definitive Radiotherapy for Elderly Patients with Locally Advanced Squamous Cell Head and Neck Cancer (LAHNSCC): A Single-Institution Experience

Cisplatin and 5-fluorouracil with or without epidermal growth factor receptor inhibition panitumumab for patients with non-resectable, advanced or metastatic oesophageal squamous cell cancer: a prospective, open-label, randomised phase III AIO/EORTC trial (POWER)

Palliative chemotherapy of advanced oesophageal squamous cell cancer (ESCC) consists of cisplatin/5-fluorouracil (CF) to target epidermal growth factor receptor (EGFR) with panitumumab (P); chemotherapy enhanced overall survival (OS) in advanced colorectal or squamous cell head and neck cancers. With prospective serum and tumour biomarkers, we tested if P added to CF (CFP) improved OS in advanced ESCC. Eligible patients with confirmed ESCC that was not curatively resectable or did not qualify for definitive radiochemotherapy, were randomised 1 : 1 to receive CF [cisplatin (C) 100 mg/m2 i.v., day 1; 5-fluorouracil (F) 1000 mg/m2 i.v., days 1-4] or CF plus P (9 mg/kg, i.v., day 1, each q3-week cycle) until progressive disease or unacceptable toxicity. Safety was reviewed by the Data Safety Monitoring Board after 40, 70 and 100 patients who completed at least one cycle. After 53 enrolled patients, cisplatin was reduced from 100 mg/m2 to 80 mg/m2. The trial was stopped early based on interim efficacy results triggered by the third safety analysis: median OS (mOS) favoured CF over CFP, regardless of cisplatin dose [hazard ratio (HR) 1.77, 95% confidence interval (CI) 1.06-2.98; P= 0.028]. In the final analysis, mOS was 10.2 versus 9.4 months for CF versus CFP, respectively (HR 1.17, 95% CI 0.79-1.75; P= 0.43). One hundred (70.4%) of 142 patients in the safety population died, 51 (51.0%) with CFP. Most deaths were related to disease progression [44/49 (90%) deaths in CF versus 34/51 (67%) deaths in CFP]; objective responses [27/73 (37.0%)] were identical. The most common serious adverse events were kidney injury [3 (4.3%) versus 7 (9.7%)], general health deterioration [5 (7.1%) versus 5 (6.9%)] and dysphagia [4 (5.7%) versus 4 (5.6%)] in CF versus CFP, respectively. There were three (4.3%) and 17 (23.6%) common terminology criteria for adverse events (CTCAE) grade 5 events in CF versus CFP, respectively. Low soluble (s)EGFR levels were associated with better progression-free survival; sEGFR was induced under CFP. EGFR inhibition added to CF did not improve survival in unselected advanced ESCC patients. The results support further liquid biopsy studies. ClinicalTrials.gov (NCT01627379) and EudraCT (2010-020606-15).

Optimal Dose of Cisplatin (CDDP) Given Concurrently with Radiotherapy (RT) in Locally Advanced Squamous Cell Head and Neck Cancer (SQC HNC)

Optimal Dose of Cisplatin (CDDP) Given Concurrently with Radiotherapy (RT) in Locally Advanced Squamous Cell Head and Neck Cancer (SQC HNC)

EP1.04-23 Ongoing Phase II Trial of Anti-PD1 Therapy in Combination with CIMAvax-EGF in Patients with Advanced NSCLC or Squamous Cell Head and Neck Cancer

CIMAvax-EGF (CE) is a novel EGF-depleting immunotherapy consisting of human recombinant EGF conjugated to recombinant P64k derived from Neisseria meningitidis, that elicits an anti-EGF antibody response, resulting in reduction of circulating EGF levels. A randomized phase III study of CIMAvax-EGF administered after first-line platinum-based chemotherapy as switch maintenance therapy, in patients with advanced NSCLC, demonstrated improved overall survival versus best supportive care alone, particularly in patients with high baseline serum EGF levels. A recently completed phase I trial combining CE with nivolumab (N), an anti-PD1 immune checkpoint inhibitor, as second-line therapy for advanced NSCLC, demonstrated the combination is safe and induces a higher frequency of good anti-EGF antibody responses compared to the historical experience with CE alone (Figure 1). In addition, promising efficacy was observed in patients with PD-L1 low (< 1%) tumors. These results led to the initiation of this multi-arm phase II trial. CIMAvax-EGF (2.4 mg IM every 2 weeks x 4 doses, then every 4 weeks thereafter) in combination with Nivolumab (240mg IV every 2 weeks) is being evaluated in this multi-arm phase II study (NCT02955290) as second-line therapy in patients with advanced NSCLC (cohort A), advanced/recurrent head and neck squamous cell cancer (cohort B) and is also being tested as first-line therapy in combination with pembrolizumab (200 mg IV every 4 weeks) in patients with advanced NSCLC with PD-L1 ≥50% (cohort C). The primary and secondary endpoints are to evaluate 12-month OS and PFS in cohorts A and B, and to evaluate objective response rate, PFS and 12-month OS in cohort C. Exploratory objectives include characterizing tissue-based immune and EGFR signaling as well as serum EGF levels, anti-EGF antibody levels and other blood-based biomarkers in relation to clinical outcomes. A total of 10 patients have been enrolled to this ongoing study with a planned enrollment of up to 127 patients. An update on accrual along with interim safety, efficacy and correlative data will be presented. To date, the combination of CIMAvax-EGF with anti-PD1 therapy has been safe and well tolerated. Enrollment to the phase II portion of this study is ongoing at Roswell Park and is in the process of being expanded to additional U.S. sites.

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).

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 &amp; 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.

Efficacy and Safety of Cetuximab plus Radiotherapy in Cisplatin-Unfit Elderly Patients with Advanced Squamous Cell Head and Neck Carcinoma: A Retrospective Study

Introduction: Concurrent platinum-based chemoradiation currently represents the standard treatment for advanced head and neck cancer (HNC), but it induces a significant toxicity, in particular among elderly patients. Elderly and unfit patients have been underrepresented in clinical trials and there is a need for tailored guidelines. Methods: A retrospective review of clinical data of HNC patients treated at the Operative Oncology Unit of the San Giovanni di Dio Hospital in Frattamaggiore (Naples, Italy) was performed. At study entry, a comprehensive assessment including absolute contraindications for cisplatin use, as well as comorbidities, socioeconomic status, BMI, and weight loss, was performed. The treatment included high-dose radiotherapy plus weekly cetuximab (initially at a dose of 400 mg/m2of body surface area and thereafter at 250 mg weekly during the whole radiotherapy). The aim of this study was to evaluate the activity and toxicity of this schedule in a series of patients aged older than 69 years. Results: Between May 30, 2013, and March 30, 2015, sixty-four patients (age range, 69–87 years; median age, 73.7 years; male/female ratio, 46/18) were treated. The overall response rate was 67% in this series of patients. The disease control rate was 76%. Disease progression was recorded in 25% of the patients. The median duration of loco-regional control was 17 months (range, 15.8–17.7 months). PFS was 14.8 months (range, 13.9–15.5 months). The overall survival was 34 months, with a median follow-up of 41.0 months (range, 31.1–36.8 months). The main grade 3/4 adverse events were acne rash in 52% and radiation dermatitis in 32% of the cases. Conclusion: Cetuximab plus radiotherapy appears to be feasible and active in elderly patients unsuitable for cisplatin treatment. The treatment was supported by a favorable toxicity profile.

Safety and efficacy of weekly versus three-weekly paclitaxel plus platinum neoadjuvant chemotherapy in patients with locally advanced squamous cell head and neck carcinoma: A pilot study

Background:Squamous cell carcinoma of head and neck (SCCHN) is one of the most common cancers seen in India and also the world. Majority of patients present in locally advanced (LA) disease where neoadjuvant combination chemotherapy with a taxane plus platinum with/without 5-Fluorouracil is the standard of care treatment. There are no/few prospective trials of weekly paclitaxel in SCCHN in spite of convincing evidence regarding safety and tolerability in other solid tumors such as breast, ovary, and lung carcinoma. In the present study, we prospectively assessed the safety and efficacy of weekly versus three-weekly paclitaxel plus platinum neoadjuvant chemotherapy in patients with LA-SCCHN.Materials and Methods:We included 50 newly diagnosed patients of LA-SCCHN in the study and randomized them into two groups to receive either low-dose weekly (80 mg/sq. m) or standard three-weekly (175 mg/sq. m) paclitaxel along with standard dose carboplatin (AUC 5) and assessed response rates and toxicities.Results:Age and sex were evenly matched in both groups. Oral and oropharyngeal cancers were the most common sites. Hematological toxicities were significantly more in the three-weekly group. Nonhematological toxicities, especially neuropathy, were also more in this group. The overall response rate (complete response + partial response) in the three-weekly arm was 36% versus 52% in the weekly arm.Conclusion:Data from our small study suggest that weekly paclitaxel plus platinum neoadjuvant chemotherapy may be superior to the standard every 3 weeks’ administration in terms of safety as well as efficacy in patients with LA-SCCHN.

Prognostic Nutritional Index as an independent prognostic factor in locoregionally advanced squamous cell head and neck cancer

BackgroundLocally advanced head and neck squamous cell carcinoma (LAHNSCC) is a heterogeneous disease in which better predictive and prognostic factors are needed. Apart from TNM stage, both systemic inflammation and poor nutritional status have a negative impact on survival.MethodsWe retrospectively analysed two independent cohorts of a total of 145 patients with LAHNSCC treated with induction chemotherapy followed by concurrent chemoradiotherapy at two different academic institutions. Full clinical data, including the Prognostic Nutritional Index (PNI), neutrophil to lymphocyte ratio and derived neutrophil to lymphocyte ratio, were analysed in a training cohort of 50 patients. Receiver operating characteristic curve analysis was used to establish optimal cut-off. Univariate and multivariate analyses of prognostic factors for overall survival (OS) were performed. Independent predictors of OS identified in multivariate analysis were confirmed in a validation cohort of 95 patients.ResultsIn the univariate analysis, low PNI (PNI<45) (p=0.001), large primary tumour (T4) (p=0.044) and advanced lymph node disease (N2b-N3) (p=0.025) were significantly associated with poorer OS in the validation cohort. The independent prognostic factors in the multivariate analysis for OS identified in the training cohort were dRNL (p=0.030) and PNI (p=0.042). In the validation cohort, only the PNI remained as independent prognostic factor (p=0.007).ConclusionsPNI is a readily available, independent prognostic biomarker for OS in LAHNSCC. Adding PNI to tumour staging could improve individual risk stratification of patients with LAHNSCC in future clinical trials.

An Ex Vivo Human Tumor Assay Shows Distinct Patterns of EGFR Trafficking in Squamous Cell Carcinoma Correlating to Therapeutic Outcomes

EGFR overexpression is associated with squamous cell carcinoma development. Altered endocytosis and polarization of receptor tyrosine kinases, including EGFR, affect migration and invasion in three-dimensional culture. These studies have been completed via genetic sequencing, cell line, or three-dimensional invitro and invivo murine models. Here, we describe an imaging method that allows exvivo examination of ligand-induced endocytosis of EGFR in non-dissociated human tumors. We analyzed sets of tumor samples from advanced cutaneous squamous cell carcinoma and head and neck squamous cell carcinoma, actinic keratosis, intraepidermal carcinoma, and cutaneous squamous cell carcinoma. We show that EGFR endocytosis is dysregulated in advanced SCC and correlates with anti-EGFR monoclonal antibody therapy outcomes. In actinic keratosis, intraepidermal carcinoma, and well-differentiated cutaneous squamous cell carcinoma, different patterns of epidermal growth factor ligand uptake and binding were observed at the leading edge of different dysplastic lesions, suggesting that these differences in EGFR endocytosis might influence the metastatic potential of dysplastic squamous epithelium. These studies in live exvivo human tumors confirm that endocytosis dysregulation is a physiological event in human tumors and has therapeutic implications.

An alternative approach with a low dose and prolonged chemotherapy for palliative treatment of locally advanced, metastatic or recurrent squamous cell head and neck cancer

BackgroundIt is expected that about 65,000 new patients will be diagnosed with head and neck cancer in 2017 in the United States. Patients with recurrent or advanced or metastatic head and neck do not have good survival due to aggressive and recurrent nature of this cancer. Moreover, cumulative and residual toxicities from previous and ongoing treatments significantly impede quality of remaining part of their life. Currently available chemotherapeutic regimens for this group are derived from the treatments used for the potentially curable disease. These regimens and associated toxicity are obviously not the best matches for the treatment with palliative intent. We here present a retrospective study where we used dose-adjusted chemotherapy specifically for palliative treatment this sub-group of head and neck cancer patients.MethodsStudy population was identified from the University of Florida, and IRB approval was obtained. We used currently available and approved chemotherapeutic agents (including Taxols, Platins, 5-Fluorouracil and Epidermal Growth Factor Receptor inhibitors) for treatment of head and neck cancer but dose-adjusted at approximate 50% dose of currently recommended doses. We then gave personalized doses for a prolonged period by titrating doses based on response and tolerability of each patient. Data was collected for treatment, response, side effects, and outcomes. KM analysis was performed for survival data.ResultsTotal of 32 patients were included in this study with a median age of 65.2 years and a median follow-up of 10.1 months. 62.5% (n = 20) had locally advanced disease and rest had metastatic disease. 37.5% (n = 12) had new disease while rest had recurrent cancer. Of 32 patients, 14 patients received TPF based while 18 patients received PFE based chemotherapy. Total of 270 chemotherapy cycles were delivered among these 32 patients. They received a median of 9 cycles (range 3–14) over a median of 6.2 months (range 1.8–21.1). With this treatment approach, we noted median progression-free survival of 14.0 months and median overall survival of 15.7 months. Notable grade 3 toxicities were generalized fatigue in 12.5% (n = 4), nausea/vomiting in 6.3% (n = 2), diarrhea in in 6.3% (n = 2), mouth soreness in 6.3% (n = 2), rash in 3.1% (n = 1), neutropenia in 18% (n = 6) and anemia in 15.6% (n = 5) while notable grade 4 toxicities were neutropenia and anaphylaxis in 3.1% (n = 1) patient each.ConclusionWith this personalized approach, we noticed minimal side effects, able to deliver prolonged therapy and obtained comparable results to previous studies.

Factors affecting adherence to standard cisplatin (CDDP)-based chemotherapy regimen for locally advanced squamous cell head and neck (H&amp;N) cancer in an inner city safety net hospital.

252 Background: The non-operative standard of care for advanced, non-metastatic H&amp;N cancer is high dose CDDP (100 mg/m2) given every 21 days for 3 cycles concurrent with radiation. Many patients are either started on or switched to an alternative regimen due to pre-treatment co-morbidities or development of CDDP related toxicity. In clinical practice, the percentage of patients not receiving current standard of care and reasons thereof are not well defined. This and the consequence of such deviation from treatment is what we propose to study. Methods: This is a retrospective study including 45 patients from 2014-2016 with advanced, non-metastatic H&amp;N cancer treated with definitive concurrent chemoradiation. All patients were evaluated by ENT, Medical and Radiation Oncology and were presented to the multidisciplinary H&amp;N Tumor board. Results: In the studied population, 73.3% were African Americans , 82.2 % males, 91.1% smokers and 97.7 % ECOG 0-1 at presentation. In all, 11.1% patients were unable to receive CDDP and received an alternate drug because of frailty, ECOG 2 status, pre-existing CKD, hearing problems or neuropathy. Of the 40 patients (88.8%) receiving CDDP, only 8 (17.7%) completed 3 cycles on schedule without changes. Of the remaining 32 (71.1%) receiving CDDP, 13 (40.6 %) were switched to alternate drug and 19 (59.3%) required only a dose decrease/delay. The reasons included CDDP related toxicity (54.05%), frailty or comorbidities (27%), worsening ECOG and fluid overload due to CDDP associated hydration. Toxicities leading to change in regimen included mostly AKI (63.15%) and also neutropenia, ototoxicity, nausea, vomiting and diarrhea. Mean duration of radiation therapy in patients receiving standard regimen was 52.2 days and in patients deviating from standard regimen was 55.1 days. Data supporting trend of poorer outcomes in those who deviate from standard regimen will be reported later. Conclusions: Majority of patients (82.2%) with advanced, non-metastatic H&amp;N cancer being treated with definitive concurrent chemoradiation deviate from standard of care CDDP regimen with at least half due to cisplatin related toxicity.

Update on squamous cell carcinoma of the head and neck: ASCO annual meeting 2017.

SummaryAt the annual ASCO meeting clinically relevant data concerning the management of advanced head and neck cancer that will influence clinical practice in the future were presented.Chemoradiation with high-dose cisplatin remains the mainstay of treatment for patients with locally advanced squamous cell head and neck cancer. Adjuvant therapy with afatinib following chemoradiation failed to show clinical benefit. The combination of bevacizumab with platinum-based chemotherapy improved progression-free survival but did not lead to a significant difference in overall survival compared to chemotherapy alone. However, the addition of immunotherapy may improve multimodal treatment concepts in locally advanced disease and new treatment combinations might overcome resistance to checkpoint inhibition.

1091P - Prognostic nutritional index (PNI) is an independent prognostic factor in locoregionally advanced squamous cell head and neck cancer (LAHNSCC)

1091P - Prognostic nutritional index (PNI) is an independent prognostic factor in locoregionally advanced squamous cell head and neck cancer (LAHNSCC)

Do selective radiation dose escalation and tumour hypoxia status impact the loco-regional tumour control after radio-chemotherapy of head & neck tumours? The ESCALOX protocol

BackgroundStandard of care primary treatment of carcinoma of locally advanced squamous cell head and neck cancer (LAHNSCC) consists of platinum-based concomitant chemo-irradiation. Despite progress in the treatment of LAHNSCC using modern radiotherapy techniques the outcome remains still poor. Using IMRT with SIB the escalation of total dose to the GTV is possible with the aim to improve clinical outcome. This study tests the hypothesis if radiation dose escalation to the GTV improves 2-year-LRC and -OS after concomitant chemo-irradiation.MethodsThe ESCALOX trial is a prospective randomized phase III study using cisplatin chemo-irradiation and the SIB-IMRT concept in patients with LAHNSCC of the oral cavity, oropharynx or hypopharynx to escalate the total dose to the GTV up to 80.5 Gy. Chemotherapy is planned either in the 1st and 5th week (cisplatin 20 mg/m2/d d 1–5 and d 29–33) or weekly (cisplatin 40 mg/m2/d) during RT. RT is delivered as SIB with total doses of 80.5 Gy/70.0 Gy/56.0 Gy with 2.3 Gy/2.0 Gy and 1.6 Gy in the experimental arm and in the control arm with 70.0 Gy/56.0 Gy with 2.0 Gy and 1.6 Gy. A pre-study with dose escalation up to 77.0 Gy/70.0 Gy/56.0 Gy with 2.2 Gy/2.0 Gy and 1.6 Gy is demanded by the German federal office of radiation protection (BfS). In the translational part of the trial 100 of the randomised patients will be investigated by 18-F-FMiso-PET-CT for the presence and behaviour of tumor hypoxia twice in the week before treatment start.DiscussionThe primary endpoint of the pre-study is acute radiation induced toxicity. Primary endpoint of the main trial is 2-year-LRC. By using the dose escalation up to 80.5 Gy to the GTV of the primary tumor and lymph nodes > 2 cm a LRC benefit of 15% at 2 years should be expected. The ESCALOX trial is supported by Deutsche Forschungsgemeinschaft (DFG); Grant No.: MO-363/4-1.Trial registrationClinicalTrials.gov Identifier: NCT 01212354, EudraCT-No.: 2010-021139-15