Locally Advanced Head And Neck Cancer Research Articles

Is it time to move from the Unidimensional RECIST 1.1 Response Assessment Criteria to a Volumetric Evaluation in the Present Era of Image-based Oncology? An Evaluation in Locally Advanced Head Neck Cancers Undergoing Treatment

AimsTumour response assessments, as per Response Evaluation Criteria in Solid Tumours (RECIST 1.1), are based on the sum of diameters (SODs) of the primary tumour (longest diameter) and/or short axis diameter of lymph nodes. This study evaluates the response categorisation as per RECIST 1.1 vs Computed tomography (CT) based volumetric assessment of RECIST (proposed as vRECIST) in locally advanced head and neck cancers (LAHNCs) undergoing treatment. Material and methodsThe pre-treatment SODs and CT estimated tumour volumes were recorded in 45 LAHNCs treated with radiotherapy (RT), chemoradiotherapy (CTRT) or thermochemoradiotherapy (HTCTRT). Tumour responses were assessed independently as per RECIST 1.1 and vRECIST by two radiation oncologists and grouped into complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD). These response groups were evaluated for the likely congruence of the two approaches, as categorised independently by these two observers. ResultsAll patients in stages III (n = 7), IVA (n = 16) and IVB (n = 22) were inoperable and had received either RT alone (n = 1), CTRT (n = 12) or HTCTRT (n = 32). Based on SODs criteria of RECIST 1.1, of the 45 patients, 5 and 40 were grouped as PR and SD by the first observer, while this changed to 34 and 10, respectively and 1 PD, with vRECIST (p < 0.001). Similarly, for the second observer, the 4 PR and 41 SD grouped using RECIST 1.1 were recategorised to 34 PR, 10 SD, and 1 PD by vRECIST (p < 0.001). Thus, a mismatch of 66.6% and 68.8%, respectively, was evident by observers first and second in categorising SD based on SODs of RECIST 1.1 vs PR on vRECIST. ConclusionsTreatment responses in LAHNCs assessed using SODs resulted in significant uncertainties and failed to reflect actual volumetric changes in tumours during treatment. It is perhaps time to consider replacing the SODs of RECIST 1.1 with vRECIST for unequivocal tumour response categorisation in the present era of image-based oncology practice.

Evaluating the Response of Hypofractionated Radiotherapy verses Conventional Radiotherapy with Concurrent Cisplatin in Advanced Fixed Node Head and Neck Carcinoma

Background: The evolution of radiotherapy over recent decades has reintroduced the hypofractionation for many tumour sites with similar outcomes to those of conventional fractionated radiotherapy. The use of hypofractionation in locally advanced head and neck cancer (LAHNC) has been already used, however, its use has been restricted to only a few countries. The aim of this trial was to evaluate the safety and feasibility of moderate hypofractionated radiotherapy (HYP-RT) with concomitant cisplatin (CDDP). Objectives: To evaluate the efficacy of hypofractionated radiotherapy in advanced unresectable head neck cancer, in terms of response rate and evaluate the local and systemic toxicities of hypofractionated regimen with symptomatic improvement of radiotherapy and treatment compliance. Methods: A total of 50 cases of locally advanced head and neck cancer (stage cT4b and/or N3) without any evidence of distant metastasis were included in this study. These 50 cases were randomly distributed into study and control group containing 25 each. Radiotherapy consists of a single fraction of 6 Gy Per week for a total of 6 weeks. If the patient received less than 6weeks of treatment, he/she was excluded from study. Total dose given was 36 Gy in 6 fractions. All the patients were treated by unilateral or bilateral portal till 24 Gy and then off cord planning was done. Patients with complete disease regression after initially planned 36 Gy (BED-57.6Gy, considering alpha/beta of 10 and corresponding EQD2-48Gy) were offered further dose escalation depending upon tumour regression status, tolerability and toxicity according to institutional guidelines. Partial responders are given no treatment up to end of treatment period. Results: Among the study and control group, incidence of carcinoma of tonsil was 12% and 20%, carcinoma of base of tongue was 24% and 16%, carcinoma larynx 16% and 24%, respectively and Hematological toxicities (reference to blood hemoglobin level), Renal (reference to blood urea) were assessed according to WHO toxicity criteria in all cases weekly up to six weeks Among the study and control group, 8% and 12% had no acute hematologic reactions (χ2 = 0.22, p &gt; 0.05), 56% and 48% had grade I hematologic reactions (χ2 = 0.32 p &gt; 0.05,), 28% and 36% had grade II hematologic reactions (χ2 = 0.36, p &gt; 0.05) and 8% and 4% had grade III hematologic reactions (χ2 = 0.35, p &gt; 0.05) respectively. No patient had had grade IV hematological toxicity. Among the study and control group, 80% and76% had no acute renal toxicity. (χ2 = 0.11, p &gt; 0.05), 20% and 24% had grade I hematologic reactions (χ2= 0.11 p &gt; 0.05). No patients from either group develop grade II, III and IV renal toxicity. Conclusions: HYP-RT with concomitant CDDP was considered feasible for LAHNC, and the rate of acute toxicity was comparable to that of standard concomitant chemoradiation. A feeding tube was necessary for most patients during treatment. Further investigation of this strategy is warranted.

Comparison of Thyroid Toxicity Profiles in Head and Neck Cancer Patients Irradiated by 3D-Conformal Radiation Therapy and Intensity-Modulated Radiation Therapy

ABSTRACT Background: In spite of recent technical advances in the radiation field, exposure to non-target organs such as the thyroid gland remains unavoidable in locally advanced head and neck cancer (LAHNC) planning, which is associated with late toxicities, and this may affect the lifestyle of cancer survivors. Aim: The purpose of this study was to estimate the incidence of thyroid toxicity in LAHNC patients treated with three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT). To establish its correlation, we have analyzed thyroid profile levels, DVH, and the doses of radiation received by the thyroid volume in both radiotherapy planning methods. Material and Method: Sixty patients with LAHNC enrolled and were divided into two groups treated with 3D-CRT (group A) and IMRT (group B). The patient’s thyroid function test, which consisted of serumT3, T4, and TSH, was done before starting radiotherapy and at 6 months and 12 months follow-up. Absolute thyroid volume, maximum dose, minimum dose, mean dose to the thyroid gland, and percentage of thyroid volume receiving as V10, V20, V30, V40, and V50 were studied. Results: After 6-month post-RT, 6.7% of patients in group A showed biochemical hypothyroidism, whereas biochemical hypothyroidism, sub-clinical hypothyroidism, and hyperthyroidism were observed in 10%, 3.3%, and 10% patients of group B, respectively. After 12 months post-RT, 23.3% of patients in group A showed hypothyroidism. In the 3DCRT group, mean T3 was significantly higher for patients with no hypothyroidism (P &lt; 0.05). Mean T4 was observed to be significantly lower in both the groups in hypothyroid patients (P &lt; 0.05). Mean TSH was significantly higher for hypothyroid patients in the IMRT group (P &gt; 0.01). The difference in thyroid volume and thyroid dose was observed to be statistically significant (P &lt; 0.05). Conclusion: The incidence of thyroid toxicity may be decreased by sparing the volume of the thyroid gland and the thyroid dose kept to a minimum. As per dosimetric parameters, &gt;V40 may predict the risk of developing hypothyroidism after irradiation in LAHNC patients. We recommend regular thyroid function tests on follow-up visits of irradiated patients of LAHNC.

A comparison of conventional and accelerated hypofractionated radiotherapy in definitive chemoradiation for locally advanced head and neck carcinoma: a retrospective cohort study.

The study evaluates accelerated hypofractionated radiotherapy (AHRT) compared to conventional fractionation radiotherapy (CFRT) in patients with locally advanced head and neck cancer (LAHNC) receiving definitive chemoradiation therapy. The study includes a retrospective cohort analysis of 120 patients. CFRT arm (n = 65) received 2 Gy per fraction to a dose of 70 Gy over 7 weeks in a three-volume approach, whereas the AHRT arm (n = 55) received 2.2 Gy per fraction to a dose of 66 Gy in 6 weeks with a two-volume approach. The primary outcome was overall survival (OS). With a median follow-up of 18.9 months, 23 patients died in the AHRT arm, and 45 deaths in the CFRT arm. The median OS was 23.4 and 37.63 months in the CFRT and AHRT arms, respectively (hazard ratio [HR] = 0.709; 95% confidence interval [CI], 0.425-1.18; p = 0.189). The median time to loco-regional control was 33.3 months in the CFRT arm and was not reached in the patient group receiving AHRT (HR = 0.558; 95% CI, 0.30-1.03; p = 0.065). The median progression-free survival was 15.9 months in the CFRT arm and 26.9 months in the AFRT arm (HR = 0.801; 95% CI, 0.49-1.28; p = 0.357). Out of 11 acute toxic deaths, eight were in the CFRT arm. The study showed a trend towards benefit in terms of locoregional control in the AHRT arm and similar OS. A longer follow-up of patients receiving AHRT is required to assess the benefit.

Utility of Prophylactic Percutaneous Gastrostomy in Patients With Head and Neck Cancer Receiving Concurrent Chemoradiotherapy: A Multicenter Analysis.

Patients with head and neck cancer (HNC) have an elevated incidence of cachexia and malnutrition due to the tumor's location interfering with oral feeding. Concurrent chemoradiation (CCRT) can have an emetic effect and cause dysphagia and oral mucositis. Adequate nutrition improves immunity, raises the response to therapy, reduces adverse effects, and improves survival. Numerous studies have suggested the utility of nutritional support from percutaneous endoscopic gastrostomy (PEG) in HNC patients. Although PEG is usually considered a safe procedure, it has a mortality rate of 0-2.2% and a risk of other procedure-related complications of 17-40%. Our work intends to evaluate the utility of PEG in patients with locally advanced HNC who underwent CCRT. We performed a cohort study at three institutions. We included patients with HNC who underwent definitive CCRT treatment from January 2013 to December 2022.The study consisted of an observational, descriptive, retrospective analysis of prespecified clinical data. Descriptive statistics were used to compare the data between the PEG group and the non-PEG group. Analysis of covariance (ANCOVA) was used forcovariance analysis. Fisher's exact test was used to compare proportional data and Student's t-test was used to assess the differences in continuous data. Survival analysis was performed using the Kaplan-Meier estimator. P-values of<0.05 were considered to be indicative of statistical significance. The SPSS Statisticsversion 28.0 (Armonk, NY: IBM Corp.) was used to perform all statistical evaluations. We identified 90 eligible patients diagnosed with local advanced HNC who had received definitive CCRT with three weekly cycles of cisplatin as follows: 44 with a prophylactic PEG tube and 46 without a prophylactic PEG tube. Most patients were male (84.4%) and 50% of patients were diagnosed with stage IVa HNC at the time of diagnosis. There wasn't an effect of PEG placement on BMI at the end of CCRT after controlling for the effect ofbaseline BMI (F {1.84}=0.065 {p=0.799}).In the study population, BMI was significantly lower after CCRT (21.30 kg/m2 vs. 23.97 kg/m2), t (86)=12.389, p<0.001. In the subgroup with baseline BMI <18.5 kg/m2 (15 patients), 90% of patients with prophylactic PEG were able to complete the three planned cycles of chemotherapy vs. 66.7% in the non-PEG group. Ten patients in the PEG group (22.7%) referredfeeding tube dependency. Patients with dysphagia were 3.2 times more likely to have placed prophylactic PEG (p=0.007). The difference in overall survivaland progression-free survivalbetween the two groups was not statistically significant (p=0.57 and p=0.497, respectively). In this study using real-world data, we found a potentially protective effect of PEG in underweight patients with locally advanced HNC performing CCRT in order to complete three cycles of treatment.

Quality of life and its correlates in pretreatment patients with locally advanced head and neck cancer: A cross-sectional study in Thailand.

Locally advanced head and neck cancer (LAHNC) can significantly impact the quality of life of patients in various ways. However, several factors can contribute to the decrease in quality of life. In Thailand, there is limited knowledge about the factors that affect the quality of life of patients with LAHNC before they receive treatment. This study aimed to examine the correlations between Palliative Performance Scale (PPS), family income, body mass index (BMI), age, comorbidity index, and the quality of life of patients with LAHNC before they undergo treatment. A correlational cross-sectional study was conducted, and data were collected from 94 pretreatment patients with LAHNC who were admitted to a cancer center in central Thailand using purposive sampling. The data collection instruments included a demographic data form, a medical record form, the Charlson Comorbidity Index (CCI), the Palliative Performance Scale (PPS), and the Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N) version 4. Descriptive statistics, Pearson's correlation, and Spearman's rank correlation were used to analyze the data. All study participants completed the questionnaire. The results showed that the overall quality of life of the patients was moderate. PPS, family income, and body mass index were moderately positively correlated with quality of life (r = 0.494, p <0.01; r = 0.420, p <0.01; r = 0.339, p <0.01, respectively). Age had a moderate negative correlation with quality of life (r = -0.596, p <0.01), while comorbidity was not significantly associated with quality of life. The quality of life of patients with LAHNC before treatment was associated with various factors, including PPS, family income, body mass index, and age. These findings highlight the importance of nutritional support before treatment and the need for social support, especially for older adult patients, to improve their quality of life. The results of this study can be valuable for nurses in developing care programs that enhance the quality of life for patients with LAHNC during the pretreatment phase.

Treatment patterns of targeted and nontargeted therapies and survival effects in patients with locally advanced head and neck cancer in Taiwan

BackgroundTaiwan’s National Health Insurance has covered targeted therapy, namely cetuximab, for locally advanced head and neck cancers (LAHNC) since July 2009. This study examines treatment trends and survival effects of locally advanced head and neck cancer patients before and after Taiwan’s National Health Insurance covered cetuximab.MethodsWe examined treatment trends and survival effects for patients with LAHNC using Taiwan’s National Health Insurance Research Database. Patients who received treatment within 6 months were categorized as either nontargeted or targeted therapy groups. We analyzed treatment trends with the Cochran-Armitage trend test and explored factors associated with treatment selection and survival effects using multivariable logistic regression and Cox proportional hazards models.ResultsOf the 20,900 LAHNC patients included in the study, 19,696 received nontargeted therapy, while 1,204 received targeted therapy. Older patients with more comorbid conditions, advanced stages and patients with hypopharynx and oropharynx cancers were more likely to receive targeted therapy with concomitant cetuximab treatment. Patients who received targeted therapy in addition to other treatment modalities had a greater risk of one-year and long-term all-cause mortality or cancer-specific mortality than those without receiving targeted therapy (P < 0.001).ConclusionsOur study found an increasing trend in cetuximab utilization among LAHNC after reimbursement in Taiwan, but overall usage rates were low. LAHNC patients receiving cetuximab with other treatments had higher mortality risk than those receiving cisplatin, suggesting cisplatin may be preferred. Further research is needed to identify subgroups that could benefit from concomitant cetuximab treatment.

The Geriatric Nutritional Risk Index as a prognostic factor in older adult patients with locally advanced head and neck cancer receiving definitive chemoradiotherapy with tri-weekly cisplatin

IntroductionConcurrent chemoradiotherapy (CCRT) is a standard treatment for locally advanced head and neck cancer (LAHNC) in the definitive setting. The Geriatric Nutritional Risk Index (GNRI) is a screening tool to predict the risk of morbidity and mortality in the older adult. Nutritional management is key during CCRT but the association between prognosis and initial nutritional status in older adults with LAHNC undergoing CCRT remains unknown. Materials and MethodsPatients ≥65 years old with LAHNC who received definitive CCRT with cisplatin (80 mg/m2 or 100 mg/m2, every three weeks, three times) between 2012 and 2018 were included. Patients without completion of radiotherapy were excluded. Patients were stratified into two groups based on the GNRI (≦98 or > 98). Overall survival (OS) and event-free survival (EFS) were analyzed by the Kaplan-Meier method and the log-rank test. The Cox proportional hazards model was adopted to identify prognostic factors. GNRI, sex, T and N categories were prespecified as variables for multivariable analysis. ResultsThe median age of 111 patients (88 male, 79%) was 69 years (interquartile range: 67–71), among which 23 patients had low GNRI (20 male, 87%) and 88 patients had high GNRI (68 male, 77%). Baseline clinical characteristics were not statistically different between the two groups. OS was significantly worse in the low GNRI group than in the high GNRI group (p = 0.048). There was no statistical difference in EFS between the two groups (p = 0.12). Multivariable analysis revealed that low GNRI (hazard ratio [HR]: 3.17, 95% confidence interval [95%CI]: 1.12–8.96, p = 0.029) and higher N category (HR: 4.37, 95% CI: 1.58–12.06, p = 0.004) were associated with worse OS. For EFS, the higher N category was significantly associated with a worse outcome (HR: 2.54, 95% CI: 1.16–5.59, p = 0.02). DiscussionPoorer nutritional status before initiation of CCRT was associated with worse OS in older adults with LAHNC in the definitive setting. The GNRI is a convenient tool for predicting OS in older adult patients with LAHNC treated with CCRT.

A prospective randomized study comparing the efficacy between povidone-iodine gargling and benzydamine hydrochloride for mucositis prevention in head and neck cancer patients receiving concurrent chemoradiotherapy

BackgroundConcurrent chemoradiation (CCRT) has been the standard treatment for organ preservation or locally advanced head and neck cancer (LAHNC). Radiation-induced oral mucositis (RIOM) is an important treatment-limiting toxicity. Benzydamine hydrochloride was recommended to prevent oral mucositis. Povidone-iodine had also been adopted to use as an oral rinse to prevent mucositis. ObjectiveThis study compared the efficacy between benzydamine hydrochloride and 0.1% povidone-iodine to prevent RIOM in HNC patients who received concurrent chemoradiotherapy. MethodsWe conducted a randomized control study in HNC patients receiving CCRT with curative intent. The stratification factors were primary site of disease, treatment modality, chemotherapy regimen, and schedule. The primary outcome was RIOM assessed by Oral Mucositis Assessment Scale (OMAS). Secondary outcomes included RIOM assessed by NCI-CTCAE, use of analgesic, antibiotics and anti-fungal drugs, hospitalization, and participant satisfaction. ResultsThere were 83 participants recruited for this study with 71 completing the trial. Demographic characteristics were well-balanced between both arms. The univariate regression analysis revealed that povidone-iodine correlated with less RIOM compared to benzydamine hydrochloride (coefficient −2.25, 95% CI -4.37 to −0.012, p-value 0.03). The incidence of grade III-IV CTCAE RIOM during the study period was 51.4% with benzydamine hydrochloride compared to 26.5% with 0.1% povidone iodine (p-value 0.032). The peak incidence of grade III-IV CTCAE RIOM occurred in the 7th week of treatment (40.5% vs. 11.8%, p-value 0.01). This indicated the efficacy of povidone-iodine to prevent severe RIOM which usually most severity in the last week of CCRT treatment. The multivariate analysis revealed that the CCRT setting (definitive vs. adjuvant) and gargling agents (povidone-iodine vs. benzydamine hydrochloride were the factors associated with RIOM. ConclusionThis study demonstrated higher efficacy of 0.1% povidone-iodine gargle than benzydamine hydrochloride in mucositis prevention.

Multi-centre radiomics for prediction of recurrence following radical radiotherapy for head and neck cancers: Consequences of feature selection, machine learning classifiers and batch-effect harmonization.

Radiomics models trained with limited single institution data are often not reproducible and generalisable. We developed radiomics models that predict loco-regional recurrence within two years of radiotherapy with private and public datasets and their combinations, to simulate small and multi-institutional studies and study the responsiveness of the models to feature selection, machine learning algorithms, centre-effect harmonization and increased dataset sizes. 562 patients histologically confirmed and treated for locally advanced head-and-neck cancer (LA-HNC) from two public and two private datasets; one private dataset exclusively reserved for validation. Clinical contours of primary tumours were not recontoured and were used for Pyradiomics based feature extraction. ComBat harmonization was applied, and LASSO-Logistic Regression (LR) and Support Vector Machine (SVM) models were built. 95% confidence interval (CI) of 1000 bootstrapped area-under-the-Receiver-operating-curves (AUC) provided predictive performance. Responsiveness of the models' performance to the choice of feature selection methods, ComBat harmonization, machine learning classifier, single and pooled data was evaluated. LASSO and SelectKBest selected 14 and 16 features, respectively; three were overlapping. Without ComBat, the LR and SVM models for three institutional data showed AUCs (CI) of 0.513 (0.481-0.559) and 0.632 (0.586-0.665), respectively. Performances following ComBat revealed AUCs of 0.559 (0.536-0.590) and 0.662 (0.606-0.690), respectively. Compared to single cohort AUCs (0.562-0.629), SVM models from pooled data performed significantly better at AUC=0.680. Multi-institutional retrospective data accentuates the existing variabilities that affect radiomics. Carefully designed prospective, multi-institutional studies and data sharing are necessary for clinically relevant head-and-neck cancer prognostication models.

Outcomes with optimal treatment in geriatric head and neck cancers – Tertiary cancer centre experience

ABSTRACT Aim: Older patients with locally advanced head and neck cancers (LA-HNC) are under-represented in clinical trials and denied standard treatment with concurrent chemo-radiation. Most are treated with radiotherapy (RT) alone. However, with the use of Intensity Modulated Radiation Therapy (IMRT) and good supportive care, even this cohort of patients can be considered for chemo-radiation. Methods and Materials: 69 patients with age &gt;65 years with LA-HNC treated between April 2015 and December 2019 in our Institute were prospectively evaluated for treatment compliance and outcomes. All patients were planned to receive 70 Gy in 33-35 fractions with IMRT and weekly Cisplatin at a dose of 40 mg/m2 (or Carboplatin-AUC-2). Loco-regional control (LRC), Overall survival (OS), and prognostic factors were evaluated. Results: Median age at presentation was 67 years (65-81). 54 were male. 64% had Karnofsky Performance Status of &gt;90. 42% had Oropharyngeal Primary. 17% had co-morbidities, 66% had T3 disease, 77% had Node positive disease, and 54% had Stage III disease. All patients completed 70 Gy and 81% patients received at least 5 (&gt;200 mg/m2) chemotherapy cycles. Acute grade-3 toxicity was seen in 20% of patients and 64% had complete response. With a median follow up of 23.6 months (3-71), OS was 53.5%. Estimated 2-year LRC was 60%; estimated 2- and 5-year OS was 53.5% and 34.3%, respectively. On univariate analysis, age &lt;70 years, Cisplatin use, limited nodal disease, Stage III, and complete response to treatment showed good OS (p &lt; 0.05). Conclusion: Definitive chemo-IMRT approach in older patients with LA-HNC is well tolerated with good clinical outcomes. Hence, older age should not be a barrier for standard treatment.

Estimation of treatment efficiency of head-and-neck cancer based on tumour control probability model

External beam radiotherapy is widely used for the treatment of the locally advanced head-and-neck cancer (LAHNC). Analysis of the developed treatment plans based on tumour control probability (TCP) models could help to estimate expected treatment results of the developed plans and to find optimal treatment schemes with respect to total dose, fractional dose and overall treatment time (OTT). In this study, the simultaneous integrated boost VMAT (SIB-VMAT) plans and sequential boost VMAT (SEQ-VMAT) plans were developed based on the anatomical data of 11 patients. Methods and Material: The data of 11 patients with LAHNC (larynx, oropharynx and oral cavity) were used. For each patient two treatment plans were developed, SIB-VMAT (70 Gy to tumour, 50 Gy to lymph nodes, 25 fractions) and SEQ-VMAT (70 Gy to tumour, 50 Gy to lymph nodes, 35 fractions). The developed plans were analysed using the Niemierko’s TCP model with Maciejewski’s parameters (TCD50 = 70.26 Gy at 49-days OTT) taking into account dose-volume histograms and OTT. Results: The developed plans resulted in high clinical treatment volume (CTV) conformity (98%-98%) for all patients, except one. The average TCP value of SIB-VMAT was equal to 99.9% due to very short OTT. The average value of TCP for SEQ-VMAT was equal to 61.0%. For one patient, the both SIB-VMAT and SEQ-VMAT plans showed zero expected efficiency due to CTV coverage 95%-95%. Conclusions: Use of TCP models allows analysis of treatment plans for each particular patient and development of different treatment schemes with increase of the total dose value, fractional dose and shortening of OTT.

Is locally advanced head and neck cancer ‘increasing’ in the Netherlands? The paradox of absolute numbers, standardized incidence rates and proportional share

BackgroundSeveral reports have indicated that locally advanced head and neck cancer (LAHNC) has increased in the past decade. However, incidence trends cannot be easily compared because slightly different definitions of LAHNC were used. AimTo investigate if the incidence of locally advanced disease (LAD) in the oral cavity, oropharynx, hypopharynx and larynx is indeed increasing over time, considering the growing and ageing population in the Netherlands. Patients and methodsData were obtained from the Netherlands Cancer Registry (NCR). Primary head and neck squamous cell carcinomas of the oral cavity, oropharynx, hypopharynx and larynx diagnosed between 1989 and 2017 were included. Yearly numbers and European standardized incidence rates (ESRs) were reported by extent of disease. The annual percentage change (APC) over time in ESRs was calculated to assess trends. ResultsAbsolute numbers and ESRs of LAD increased over time for oral cavity and most prominently for oropharynx carcinomas (before 1996, APC: 0.4, 95%CI: 0.1; 0.8 and APC: 5.7 (95%CI: 3.1; 8.4) after 1996: 1.5 (1.0; 2.0) respectively. For hypopharynx cancer the absolute number and ESR of LAD increased until 1997 and declined with 0.8% per year since 1997. Absolute numbers of patients with larynx cancer stayed stable over time, while ESR decreased (APC: −0.8 (95%CI: −1.1; −0.6)). ConclusionThe perception of an increasing trend in LAD in the Netherlands can be attributed to the increasing incidence of oral cavity and oropharynx carcinomas. For LAD of the hypopharynx a decreasing trend was observed. In larynx cancer, the proportional share of LAD of the larynx increased, even though incidence rates declined.

Traditional risk factors and nodal yield-still relevant with high-quality risk-adapted adjuvant treatment for locally advanced head and neck cancer?

Patients with locally advanced head and neck cancer (LAHNC) often undergo multimodal therapy including radical resection of the primary tumor and neck dissection (ND) followed by risk-adapted adjuvant radio(chemo)therapy (R(C)T). Quality parameters influencing local control and survival of these patients have been postulated: resection status (Rstatus), extranodal extension (ENE), interval to adjuvant treatment ≤6weeks, R(C)T given when indicated, and nodal yield (NY) ≥18lymph nodes per neck. For other solid tumors the trend is towards less extensive lymph node surgery to avoid toxicity such as lymphedema, damage to peripheral nerves, dysesthesia, or paresthesia. The present study aims to investigate whether the number of nodes removed during neck dissection for LAHNC is still predictive for outcome when patients receive risk-adapted adjuvant treatment according to current guidelines. Between 2008 and 2015, 468 patients with LAHNC undergoing R(C)T with curative intent were prospectively registered in adatabase (UICCIII/IV). Among them, 359 patients received adjuvant treatment and 295 underwent neck dissection. There were 119 (40%) patients with an oropharyngeal primary, 49 (17%) with cancer of the larynx/hypopharynx, 88 (30%) of the oral cavity, and 39 (13%) of the nasal/paranasal sinuses and cancer of unknown primary (CUP). Median follow-up was 45.6months. Histopathology revealed anR1 status in65 (22%) cases and ENE in93 (31%) cases. 150 (51%) patients received RCT; the median time to adjuvant treatment from the day of tumor resection was 44days (35-54) and overall treatment time (OTT; time from surgery to the last day of R(C)T) was 90days (82-101). Factors influencing disease-free survival (DFS) were adjusted and analyzed using CART analysis (removed nodes, number of positive nodes, body mass index (BMI), ENE, T and Nclassification, Rstatus, and primary site). Local control (LC), distant metastases-free survival (DMFS), and overall survival (OS) were analyzed using Kaplan-Meier statistics and multivariate analysis (MVA) for factors predictive for DFS and OS. CART analysis(Classification and Regression Trees) showed that T classification (T3/4) is the most important predictor for DFS, followed by age (> 61 years) and BMI (< 17.4). Primary site (OPC vs. other) and number of removed nodes (< 17) were shown to be less important for DFS, while ECE, Nclassification, and Rstatus seem to be of little relevance. MVA revealed number of positive nodes, non-OPC, and T3/4 to be negative predictive factors for DFS. For OS, the number of positive nodes and non-OPC primary were predictive. Five-year rates were 86.1% for LC, 87.9% DMFS, 76.5% DFS, and 67.2% for OS. In this patient cohort, the number of removed nodes is not relevant for DFS and OS, while the number of positive nodes and Tclassification have anegative impact on these endpoints. The high-risk factors positive resection margin and ECE seem to lose their negative impact on DFS and OS. High-quality care in head and oncology is only possible within aclose multidisciplinary team and network.

Tumor Outcomes for ROMAN: Phase 3 Trial of Avasopasem Manganese (GC4419) for Severe Oral Mucositis (SOM) in Patients Receiving Chemoradiotherapy (CRT) for Locally Advanced Head and Neck Cancer (LAHNC)

<h3>Purpose/Objective(s)</h3> Intensity-modulated radiotherapy (IMRT) plus cisplatin is an established treatment for LAHNC, but ∼70% of patients develop SOM (WHO grade [gr] 3 or 4), limiting their ability to eat solids (gr 3) or liquids (gr 4), and often requiring feeding tube nutrition. There are no US-approved drugs to reduce SOM in LAHNC. A radiotherapy (RT)-induced burst of superoxide initiates oral mucositis (OM) development (Sonis 2004). Avasopasem (GC4419, AVA) is an investigational selective small molecule dismutase mimetic designed to convert superoxide to hydrogen peroxide, which may protect normal cells from, and potentially sensitize cancer cells to, RT (Riley DP 2006, El-Mahdy 2020). In a randomized, double-blind phase 2b trial, AVA reduced duration and incidence of SOM due to CRT for LAHNC vs placebo (PBO) (Anderson 2019) and maintained 2-yr tumor outcomes. The present trial (NCT03689712) further assessed safety and efficacy of AVA to reduce SOM due to CRT for LAHNC of the oral cavity (OC) or oropharynx (OP). <h3>Materials/Methods</h3> Double-blind, PBO-controlled trial; patients receiving 60-72 Gy of IMRT (≥50 Gy to ≥2 OM sites) plus cisplatin (weekly or q3 weeks) were randomized 3:2 to IV AVA 90 mg vs PBO M-F before each RT fraction. OM by the WHO scale was assessed by trained evaluators biweekly during RT & weekly for 2 weeks thereafter. Primary endpoint: SOM (WHO gr 3 or 4) incidence through the end of IMRT. Secondary endpoints included SOM duration through 2 weeks post-IMRT, gr 4 OM incidence through the end of IMRT, and tumor outcomes. <h3>Results</h3> N=455 randomized, 407 (241 AVA/166 PBO) primary analysis population; med. age 61; 86% male; 82% OP. Statistically significant 16% relative reduction in SOM incidence (54% vs 64%; <i>p</i>=0.045) and 56% relative reduction in SOM duration (median, 8 vs 18 days; <i>p</i>=0.002) were observed. Gr 4 incidence was reduced 27% (<i>p</i>=0.052). Improvement was seen in multiple secondary and exploratory endpoints (table). Adverse event frequencies were comparable between treatment groups without clear AVA-specific toxicity or increase in cisplatin-attributable toxicity. Available tumor outcome data will be reported. <h3>Conclusion</h3> AVA produced statistically significant, clinically meaningful improvement of SOM vs PBO that was consistent across multiple measures of SOM, with an adverse event profile consistent with expectations for IMRT/cisplatin. Tumor outcomes will be reported. Funder Galera Therapeutics, Inc.

696P Geriatric nutritional risk index as a prognostic factor in elderly patients with locally advanced head and neck cancer receiving definitive chemoradiotherapy with cisplatin

Concurrent chemoradiotherapy (CCRT) is a standard treatment for locally advanced head and neck cancer (LAHNC) in the definitive setting. The Geriatric Nutritional Risk Index (GNRI) is a screening tool to predict the risk of morbidity and mortality in the elderly. Nutritional management is key during CCRT but the association between prognosis and initial nutritional status in elderly patients with LAHNC undergoing CCRT remains unknown.

Outcomes With Optimal Treatment in Geriatric Head and Neck Cancers – Tertiary Cancer Centre Experience

Aim: Older patients with locally advanced head and neck cancers (LA-HNC) are under-represented in clinical trials and denied standard treatment with concurrent Chemo-radiation. Most are treated with Radiotherapy (RT) alone. However, with the use of Intensity Modulated Radiation Therapy (IMRT) and good supportive care, even this cohort of patients can be considered for chemo-radiation. Methods and Materials: 69 patients with age &gt;65 years with LA-HNC treated between April 2015 and December 2019 in our Institute were prospectively evaluated for treatment compliance and outcomes. All patients were planned to receive 70Gy in 33-35 fractions with IMRT and weekly Cisplatin at a dose of 40mg/m2 (or Carboplatin-AUC-2). Loco-regional Control (LRC), Overall survival (OS) and prognostic factors were evaluated. Results: Median age at presentation was 67 years (65-81). 54 were male. 64% had Karnofsky Performance Status of &gt;90. 42% had Oropharyngeal Primary. 17% had co-morbidities. 66% had T3 disease, 77% had Node positive disease. 54% had stage III disease. All patients completed 70Gy. 81% patients received at least 5 (&gt;200mg/m2) chemotherapy cycles. Acute Grade3 toxicity was seen in 20% of patients. 64% had complete response. With a median follow up of 23.6 months (3-71), OS was 53.5%. Estimated 2-year LRC was 60%; estimated 2- and 5-year OS was 53.5% and 34.3% respectively. On Univariate analysis, age &lt;70 years, Cisplatin use, limited nodal disease, Stage III and complete response to treatment showed good OS (p&lt;0.05). Conclusion: Definitive chemo-IMRT approach in older LA-HNC is well tolerated with good clinical outcomes. Hence older age should not be a barrier for standard treatment.

Prediction of Incomplete Response of Primary Tumour Based on Clinical and Radiomics Features in Inoperable Head and Neck Cancers after Definitive Treatment.

Radical treatment of patients diagnosed with inoperable and locally advanced head and neck cancers (LAHNC) is still a challenge for clinicians. Prediction of incomplete response (IR) of primary tumour would be of value to the treatment optimization for patients with LAHNC. Aim of this study was to develop and evaluate models based on clinical and radiomics features for prediction of IR in patients diagnosed with LAHNC and treated with definitive chemoradiation or radiotherapy. Clinical and imaging data of 290 patients were included into this retrospective study. Clinical model was built based on tumour and patient related features. Radiomics features were extracted based on imaging data, consisting of contrast- and non-contrast-enhanced pre-treatment CT images, obtained in process of diagnosis and radiotherapy planning. Performance of clinical and combined models were evaluated with area under the ROC curve (AUROC). Classification performance was evaluated using 5-fold cross validation. Model based on selected clinical features including ECOG performance, tumour stage T3/4, primary site: oral cavity and tumour volume were significantly predictive for IR, with AUROC of 0.78. Combining clinical and radiomics features did not improve model’s performance, achieving AUROC 0.77 and 0.68 for non-contrast enhanced and contrast-enhanced images respectively. The model based on clinical features showed good performance in IR prediction. Combined model performance suggests that real-world imaging data might not yet be ready for use in predictive models.

EPH68 Targeted Therapy and Treatment Trends in Locally Advanced Head and Neck Cancer in Taiwan: A Population-Based Retrospective Study

Taiwan's National Health Insurance has covered targeted therapy, namely cetuximab, for locally advanced head and neck cancers (LAHNC) since July 2009. This study aimed to estimate the trends of first-course treatment modalities before and after cetuximab was reimbursed in Taiwan and examine factors associated with targeted therapy among patients with LAHNC.

Prognostic Value of Radiological Extranodal Extension Detected by Computed Tomography for Predicting Outcomes in Patients With Locally Advanced Head and Neck Squamous Cell Cancer Treated With Radical Concurrent Chemoradiotherapy.

ObjectiveExtra Nodal Extension (ENE) assessment in locally advanced head and neck cancers (LAHNCC) treated with concurrent chemo radiotherapy (CCRT) is challenging and hence the American Joint Committee on Cancer (AJCC) N staging. We hypothesized that radiology-based ENE (rENE) may directly impact outcomes in LAHNSCC treated with radical CCRT.Materials and MethodsOpen-label, investigator-initiated, randomized controlled trial (RCT) (2012–2018), which included LAHNSCC planned for CCRT. Patients were randomized 1:1 to radical radiotherapy (66–70 grays) with concurrent weekly cisplatin (30 mg/m2) [cisplatin radiation arm (CRT)] or same schedule of CRT with weekly nimotuzumab (200 mg) [nimotuzumab plus CRT (NCRT)]. A total of 536 patients were accrued and 182 were excluded due to the non-availability of Digital Imaging and Communications in Medicine (DICOM) computed tomography (CT) data. A total of 354 patients were analyzed for rENE. Metastatic nodes were evaluated based on five criteria and further classified as rENE as positive/negative based on three-criteria capsule irregularity with fat stranding, fat invasion, and muscle/vessel invasion. We evaluated the association of rENE and disease-free survival (DFS), loco-regional recurrence-free survival (LRRFS), and overall survival (OS).ResultsA total of 244 (68.9%) patients had radiologically metastatic nodes (rN), out of which 140 (57.3%) had rENE. Distribution of rENE was balanced in the two study groups CRT or NCRT (p-value 0.412). The median follow-up period was 39 months (ranging from 35.5 to 42.8 months). Complete response (CR) was seen in 204 (57.6%); incomplete response (IR), i.e., partial response plus stable disease (PR + SD), in 126 (35.6%); and progressive disease (PD) in 24 (6.8%). rENE-positive group had poor survival compared to rENE-negative group 3-year OS (46.7% vs. 63.6%), poor DFS (48.8% vs. 87%), and LRRFS (39.9% vs. 60.4%). rENE positive had 1.71 times increased risk of IR than rENE negative. Overall stage, site, clinical metastatic node (cN), response, and rENE were the significant factors for predicting OS, DFS, and LRRFS on univariate analysis. After making adjustment on multivariate analysis, rENE was an independent prognostic factor for DFS and trending to be significant for OS.ConclusionPre-treatment rENE is an independent prognostic marker for survival in patients with LAHNSCC treated radically with CCRT that can be used as a potential predictive marker for response to treatment and hence stratify patients into responders vs. non-responders. We propose the mahajan rENE grading system applicable on CT, magnetic resonance imaging, positron emission tomography–contrast-enhanced CT, and ultrasound.