Locally Advanced Head And Neck Cancer Patients Research Articles

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 < 0.05). Mean T4 was observed to be significantly lower in both the groups in hypothyroid patients (P < 0.05). Mean TSH was significantly higher for hypothyroid patients in the IMRT group (P > 0.01). The difference in thyroid volume and thyroid dose was observed to be statistically significant (P < 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, >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.

"I have cancer during COVID; that's a special category": a qualitative study of head and neck cancer patient and provider experiences during the COVID-19 pandemic.

PurposeThe COVID-19 pandemic has drastically changed cancer care delivery strategies. Patients with locally advanced head and neck cancer (LA-HNC) may be particularly affected by the COVID-19 pandemic, as they often undergo treatments that require daily clinic visits (e.g., radiation therapy). The goal of this study was to characterize the lived experience of LA-HNC patients and their healthcare providers during the COVID-19 pandemic.MethodsLA-HNC patients who completed a full course of chemotherapy and radiation therapy during the COVID19 pandemic (N = 20) and LA-HNC healthcare providers (N = 13) participated in semi-structured interviews. Interviews were audio-recorded, transcribed verbatim, and analyzed for qualitative themes.ResultsThe COVID-19 pandemic had a significant impact on patients’ overall quality of life and health care. Results were organized in four main themes: (1) increased psychological distress; (2) exacerbated social isolation; (3) added stress in clinic for patients and providers; and (4) delays in health care.ConclusionsFindings highlight myriad ways LA-HNC patients and providers have been affected by the COVID-19 pandemic. Results can inform the development of supportive interventions to assist LA-HNC in managing COVID-19-related stress and unmet needs related to social isolation and in-clinic support.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00520-021-06773-x.

Role of the Appendicular Skeletal Muscle Index for Predicting the Recurrence-Free Survival of Head and Neck Cancer.

Background: This study investigates whether the appendicular skeletal muscle index (ASMI) was an independent prognostic predictor for patients with locally advanced head and neck cancer (LAHNC) receiving concurrent chemoradiotherapy (CCRT) and whether there were any differences in lean mass loss in different body regions during CCRT. Methods: In this prospective study, we analyzed the clinicopathological variables and the total body composition data before and after treatment. The factors associated with the 2-year recurrence-free survival rate (RFSR) were analyzed via logistic regression analysis. Results: A total of 98 patients were eligible for analysis. The body weight, body mass index, and all parameters of body composition significantly decreased after CCRT. The pretreatment ASMI was the only independent prognostic factor for predicting the 2-year RFSR (hazard ratio, 0.235; 95% confidence interval, 0.062–0.885; p = 0.030). There was at least 5% reduction in total lean and fat mass (p < 0.001); however, the highest lean mass loss was observed in the arms (9.5%), followed by the legs (7.2%), hips (7.1%), waist (4.7%), and trunk (3.6%). Conclusions: The pretreatment ASMI was the only independent prognostic predictor for the 2-year RFSR of LAHNC patients undergoing CCRT. Asynchronous loss of lean mass may be observed in different body parts after CCRT.

Toxicity syndrome and early competing deaths in head-and-neck cancer undergoing radiation therapy: Observation and hypothesis

Radiotherapy (RT) and/or concurrent chemoradiation (CRT) is the mainstay for the treatment of locally advanced head-and-neck cancer (LAHNC). Sepsis remains a poorly understood and unrecognized event in head-and-neck cancer. The study aims to hypothesize a ‘toxicity syndrome’ leading to sepsis and subsequent sepsis-related deaths. A retrospective audit of all 125 LAHNC patients treated radically from January 2013 to June 2017 was conducted. A total of fifteen toxic deaths were reported. Thirteen deaths were attributed to sepsis. Individual toxicity for death was ascertained only for three cases. A toxicity syndrome namely ‘mucositis-dysphagia-aspiration-sepsis (MDAS) complex’ was proposed as the cause of death in the rest ten cases. The authors recommend the surveillance of the ‘MDAS complex’ for the prevention of early toxicity-related deaths in patients with LAHNC undergoing RT or CRT.

Impact of antibiotic use during curative treatment of locally advanced head and neck cancers with chemotherapy and radiotherapy

BackgroundPre-clinical evidence suggests reduced efficacy of anticancer treatment in patients exposed to broad-spectrum antibiotics. It is hypothesised that this phenomenon may be explained by the effects of antibiotics on the composition of the microbiota. To assess this in a clinical setting, we analysed the impact of antibiotics in patients with locally advanced head and neck cancer (LAHNC) treated with curative intent with chemotherapy and radiotherapy (RT). Material and methodsRetrospective data for LAHNC patients treated with curative intent (245 induction chemotherapy followed by chemoradiation [CRT], 17 surgery followed by post-operative CRT, six CRT, three RT alone and one RT with concurrent cetuximab) were analysed. We evaluated the impact of antibiotics prescribed during primary anti-cancer treatment on progression-free survival (PFS), overall survival (OS) and disease-specific survival (DSS) rates by multivariate Kaplan–Meier and Cox proportional hazards regression analysis. ResultsAmong 272 patients, those receiving antibiotics between within 1 week before and 2 weeks after treatment (N = 124) progressed significantly earlier and had lower OS and DSS rates. In the multivariate analysis, administration of antibiotics was independently associated with reduced PFS (hazards ratio [HR] 1.98, P = 0.001), OS (HR 1.85, P = 0.001) and DSS (HR 1.95, P = 0.004). This effect was maintained with independence of reason for prescription, type and time of antibiotic prescription. The negative impact was greater for patients who received two or more courses of antibiotics. Antibiotic treatment was correlated with increased risk of locoregional relapse. ConclusionsOur data suggest a negative impact of antibiotic therapy on treatment outcomes following CRT with curative intent in patients with LAHNC. This potential harm should be considered when prescribing broad-spectrum and prophylactic antibiotics for such patients.

Retrospective analysis of baseline clinical factors associated to CDDP-nephrotoxicity in locally advanced head and neck cancer (LAHNC) patients.

e17537 Background: CDDP is the standard of care for HNC. We performed a retrospective analysis related to baseline clinical characteristics and CDDP-nephrotoxicity in LAHNC patients (pts) treated in a curative setting with CDDP and concomitant RT (CRT) or with CDDP as part of induction chemotherapy. Methods: We collected data of LAHNC pts treated between 2008 and 2018 at the National Cancer Institute of Milan. CDDP was administered 100 mg/sm every 3 weeks or 50 mg/sm once a week during CRT, or 75 mg/sm during induction. Nephrotoxicity was assessed using creatinine increase (CreaIncr) recorded at day 6-20 post CDDP, graded according to CTCAE v4.0 and analyzed as a dichotomous variable (Grade&gt;0 vs Grade = 0). We used univariable logistic regression to investigate associations between CreaIncr and clinical variables. Continuous variables were modeled using 3-knots restricted cubic splines. Results: Overall, 204 pts were considered. Male: 74%; median age: 56 yrs [IQR 51-63]. CRT was performed in 179 pts (88%). Three-weekly schedule was performed in 75% of pts. The median CDDP dose was 250 mg [IQR 200-300]. One fourth had history of hypertension and 9% were on diuretics. At baseline, median [IQR] creatinine was 0.80 mg/dL [0.69-0.89], creatinine clearance 109 mL/min [98-129] and uricaemia 4.90 mg/dL [4.11-5.74]. In total, 44% pts suffered from CreaIncr (G1: 46 pts; G2: 39 pts; G3-G4: 5 pts) all of them occurred within the first 2 cycles. CreaIncr was observed in 92% of pts treated with CRT, 84% received 3-weekly CDDP. Baseline creatinine clearance, azotaemia and hypertension were not significantly associated with CreaIncr. Loop diuretics alone appeared a potential relevant factor [OR 4.72;95%CI 0.96-23.32;p = 0.057]. Concomitant drugs (ACE inhibitors, Sartans, Ca-blockers) [OR 1.48;95%CI 1.00-2.18;p = 0.050] and uricaemia [OR 1.95;95%CI 1.27-3.0;p = 0.006] were statistically significantly associated to CreaIncr. Conclusions: In our selected population we found that concomitant medications and uricaemia were significantly related to CreaIncr. A better understanding of clinical baseline factors may improve decision making in a setting where CDDP has a curative significance.

Comparison between hypo-fractionated dose-escalated volumetric modulated arc therapy and conventional concurrent chemo-radiation in locally advanced head and neck cancer: a pilot study

AbstractObjective:In the treatment of locally advanced head and neck cancer (LA-HNC), both dose escalation and hypo-fractionation can improve tumour control rates with uncertain role of addition of concurrent chemotherapy. We aimed at developing a new radiotherapy protocol for patients not eligible to receive the standard concurrent chemo-radiation therapy (CCRT) with little toxicity profile.Methods:A total of 63 LA-HNC patients were randomised to receive either: 70 Gy in 35 fx in 7 weeks concurrently with cisplatin 100 mg/m2 every 3 weeks for 3 doses (Arm A) or 74 Gy in 33 fx in 6·5 weeks (Arm B). Volumetric modulated arc therapy plans were created for both treatment arms. We compared the local control (LC), progression-free survival (PFS), overall survival (OS) and acute and late toxicity between the two arms.Results:A total of 33 patients were in Arm A versus 30 patients in Arm B with median follow-up 24·2 months. No significant differences in LC, PFS and OS between the two arms. Complete remission occurred in 54·5 and 63·3% of patients in Arms A and B, respectively. All toxicities were significantly less in Arm B than Arm A.Conclusion:Slightly dose-escalated hypo-fractionated regimen is safe and feasible and has comparable efficacy and less acute and late side effects than conventional dose CCRT with avoidance of chemotherapy-related toxicities in LA-HNC patients.

Impact of hypofractionated schemes in radiotherapy for locally advanced head and neck cancer patients.

To analyze two cohorts of locally advanced head and neck cancer (LAHNC) patients treated with two schedules of hypofractionated radiotherapy and 5 versus 3 mm clinical target volume-planning target volume (CTV-PTV) margins. 145 patients were included. The patient cohort was divided into two groups. Group A included 97 patients treated with 69.96/54.45 grays (Gy) to the high-risk and low-risk volumes, respectively, in 33 fractions, with 5 mm margins. Group B included 48 patients treated with 66/54 Gy in 30 fractions using 3 mm margins. Toxicity was recorded according to the Common Toxicity Criteria version 3. Patient outcomes for locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) were determined. Median follow-up was 26 months. In terms of toxicity, acute dysphagia worsened significantly (P = 0.003) in group B, whereas acute salivary toxicity tended to significance (P = 0.071). No significant late toxicity differences were recorded. Rates of LRC at 1 and 2 years were 90.1% ± 2.6% and 84.2% ± 3.4%, respectively, with superiority for group A (P = 0.045). The statistical significance remained for the low-dose level (P = 0.007) but not for high dose (P = 0.110). Rates of DFS at 1 and 2 years were 84.9% ± 3.1% and 76.5% ± 3.9%, respectively, whereas rates of OS were 95.9% ± 1.8% and 91.6% ± 2.7%, respectively. No differences were observed between the two groups in terms of DFS (P = 0.270) and OS (P = 0.152). The use of reduced CTV to PTV margins and dose reduction with hypofractionation schedule can improve the pattern of toxicity in LAHNC patients. This approach resulted in an increased rate of locoregional progression, particularly in low-risk regions. 4 Laryngoscope, 130:E163-E170, 2020.

Genetic Variants as Predictive Markers for Ototoxicity and Nephrotoxicity in Patients with Locally Advanced Head and Neck Cancer Treated with Cisplatin-Containing Chemoradiotherapy (The PRONE Study).

Ototoxicity and nephrotoxicity are potentially irreversible side effects of chemoradiotherapy with cisplatin in locally advanced head and neck cancer (LAHNC) patients. Several predictive genetic variants have been described, but as yet none in LAHNC patients. The aim of this study is to investigate genetic variants as predictors for ototoxicity and nephrotoxicity in LAHNC patients treated with cisplatin-containing chemoradiotherapy. Our prospective cohort of 92 patients was genotyped for 10 genetic variants and evaluated for their association with cisplatin-induced ototoxicity (ACYP2, COMT, TPMT and WFS1) and nephrotoxicity (OCT2, MATE and XPD). Ototoxicity was determined by patient-reported complaints as well as tone audiometrical assessments. Nephrotoxicity was defined as a decrease of ≥25% in creatinine clearance during treatment compared to baseline. A significant association was observed between carriership of the A allele for rs1872328 in the ACYP2 gene and cisplatin-induced clinically determined ototoxicity (p = 0.019), and not for ototoxicity measured by tone audiometrical assessments (p = 0.449). Carriership of a T allele for rs316019 in the OCT2 gene was significantly associated with nephrotoxicity at any time during chemoradiotherapy (p = 0.022), but not with nephrotoxicity at the end of the chemoradiotherapy. In conclusion, we showed prospectively that in LAHNC patients genetic variants in ACYP2 are significantly associated with clinically determined ototoxicity. Validation studies are necessary to prove the added value for individualized treatments plans in these patients.

SY5-3 - Role of radiotherapy for multidisciplinary treatment of head and neck cancer

Definitive radiotherapy (RT) plays an essential role for locally advanced head and neck cancer (LAHNC), especially for organ preservation. Although RT can show clear benefit in minimal invasive therapy regarding both organ preservation and better patient's QOL, the tumor control of LAHNC was insufficient. Thus, multidisciplinary approach was required in improving efficacy of definitive RT. Concurrent chemoradiotherapy (CCRT) with platinum agents was believed as standard modality because of improving tumor control, while increasing radiation morbidity sometimes became significant problems. Even if CCRT was administered, local failure still remained essential problem for LAHNC after CCRT, thus, surgical intervention was sometimes needed to salvage either residual or recurrent disease. In addition, postoperative CCRT was reported to be considered for patients with high risk features such as positive surgical margin and/or extranodal extension. More intensive treatment sometimes sacrificed functional and social status of LAHNC patients, so less invasive treatment became one of the major clinical requirement for improving treatment outcome. Recently, intensity modulated radiation therapy (IMRT) has been penetrated to Japanese clinical practice for LAHNC. Using this technique, conformal dose distribution to both tumor and microscopic tumor burden could be achieved with sufficient dose-sparing to the normal tissue. Thus, IMRT could allow to minimize late radiation morbidity, especially for xerostomia without sacrificing treatment efficacy. IMRT is believed to useful modality for LAHNC at both definitive and adjuvant setting. More sophisticated IMRT technique would be expected to reduce dose exposure to the normal organ. Furthermore, intensity modulated proton beam therapy could reach to the further improvement of treatment quality with its physical superiority in dose distribution. Prospective trial using these high-precision RT techniques will be warranted.

PET-based prognostic survival model after radiotherapy for head and neck cancer.

The aims of this multicentre retrospective study of locally advanced head and neck cancer (LAHNC) treated with definitive radiotherapy were to (1) identify positron emission tomography (PET)-18F-fluorodeoxyglucose (18F-FDG) parameters correlated with overall survival (OS) in a training cohort, (2) compute a prognostic model, and (3) externally validate this model in an independent cohort. A total of 237 consecutive LAHNC patients divided into training (n = 127) and validation cohorts (n = 110) were retrospectively analysed. The following PET parameters were analysed: SUVMax, metabolic tumour volume (MTV), total lesion glycolysis (TLG), and SUVMean for the primary tumour and lymph nodes using a relative SUVMax threshold or an absolute SUV threshold. Cox analyses were performed on OS in the training cohort. The c-index was used to identify the highly prognostic parameters. A prognostic model was subsequently identified, and a nomogram was generated. The model was externally tested in the validation cohort. In univariate analysis, the significant PET parameters for the primary tumour included MTV (relative thresholds from 6 to 83% and absolute thresholds from 1.5 to 6.5) and TLG (relative thresholds from 1 to 82% and absolute thresholds from 0.5 to 4.5). For the lymph nodes, the significant parameters included MTV and TLG regardless of the threshold value. In multivariate analysis, tumour site, p16 status, MTV35% of the primary tumour, and MTV44% of the lymph nodes were independent predictors of OS. Based on these four parameters, a prognostic model was identified with a c-index of 0.72. The corresponding nomogram was generated. This prognostic model was externally validated, achieving a c-index of 0.66. A prognostic model of OS based on primary tumour and lymph node MTV, tumour site, and p16 status was proposed and validated. The corresponding nomogram may be used to tailor individualized treatment.

Impact of cisplatin dose intensity on human papillomavirus-related and -unrelated locally advanced head and neck squamous cell carcinoma

AimThe aim is to evaluate the impact of cisplatin dose modification on outcomes of human papillomavirus (HPV)-related (HPV+) and HPV-unrelated (HPV−) locally advanced head and neck cancer (LAHNC) treated with chemoradiotherapy (CRT). Patients and methodsA pooled analysis was conducted of stage III/IV oropharyngeal cancer (OPC), carcinoma of unknown primary (CUP) and laryngo-hypopharyngeal cancer (LHC) patients treated with single-agent cisplatin CRT in 2000–2012 from two tertiary academic cancer centres. HPV status was determined by p16 staining and/or in situ hybridisation. LHC was assumed to be HPV−. Unknown HPV status OPC/CUPs were excluded. Overall survival (OS) was calculated. Multivariable analysis (MVA) evaluated the impact of cisplatin dose intensity on survival for HPV+ and HPV− cohorts separately. ResultsA total of 404 HPV+ and 255 HPV− LAHNC (481 OPC, 18 CUP, 160 LHC) patients were included. Median follow-up was 4.3 (0.5–11.9) years. Three-year OS for cisplatin <200, =200, and >200 mg/m2 subgroups were 52%, 60%, and 72% (P = 0.001) for the HPV− and 91%, 90%, and 91% (P = 0.30) for the HPV+ patients. MVA confirmed a survival benefit with cisplatin >200 mg/m2 for the HPV− (hazard ratio [HR] 0.5, 95% confidence interval [CI]: 0.3–0.7, P < 0.001) but not for HPV+ (HR 0.6, 95% CI: 0.4–1.1, P = 0.104). There was a superior OS trend in the HPV+ T4 or N3 high-risk subset (N = 107) with cisplatin >200 mg/m2 (HR 0.5, 95% CI: 0.2–1.1, P = 0.07). ConclusionsA survival benefit of cisplatin dose >200 mg/m2 is evident for HPV− LAHNC patients, but not for HPV+ cohort overall, although the T4 or N3 subset may benefit from a higher cumulative cisplatin dose.

Induction chemotherapy with docetaxel/cisplatin/5-fluorouracil followed by randomization to two cisplatin-based concomitant chemoradiotherapy schedules in patients with locally advanced head and neck cancer (CONDOR study) (Dutch Head and Neck Society 08-01): A randomized phase II study

PurposeTo study the feasibility of induction chemotherapy added to concomitant cisplatin-based chemoradiotherapy (CRT) in patients with locally advanced head and neck cancer (LAHNC). Patients and methodsLAHNC patients were treated with 4 courses of docetaxel/cisplatin/5-fluorouracil (TPF) followed by randomization to either cisplatin 100 mg/m2 with conventional radiotherapy (cis100 + RT) or cisplatin 40 mg/m2 weekly with accelerated radiotherapy (cis40 + ART). Primary endpoint was feasibility, defined as receiving ≥90% of the scheduled total radiation dose. Based on power analysis 70 patients were needed. Results65 patients were enrolled. The data safety monitoring board advised to prematurely terminate the study, because only 22% and 41% (32% in total) of the patients treated with cis100 + RT (n = 27) and cis40 + ART (n = 29) could receive the planned dose cisplatin during CRT, respectively, even though the primary endpoint was reached. Most common grade 3–4 toxicity was febrile neutropenia (18%) during TPF and dehydration (26% vs 14%), dysphagia (26% vs 24%) and mucositis (22% vs 57%) during cis100 + RT and cis40 + ART, respectively. For the patients treated with cis100 + RT and cis40 + ART, two years progression free survival and overall survival were 70% and 78% versus 72% and 79%, respectively. ConclusionAfter TPF induction chemotherapy, cisplatin-containing CRT is not feasible in LAHNC patients, because the total planned cisplatin dose could only be administered in 32% of the patients due to toxicity. However, all but 2 patients received more than 90% of the planned radiotherapy.Clinical Trials Information: NCT00774319.

Head and Neck Cancer in the Elderly: is There Any Reason to Change Their Management?

ABSTRACT Aim: There is an increasing number of older patients diagnosed of locally advanced head and neck cancer (LA-HNC) due to the growing life expectancy. The aim of this study is to assess the suitability of bio-chemoradiation therapy (BCRT) for these patients. Methods: This multicenter retrospective study was performed in four Spanish hospitals. LA-HNC patients ≥ 70 years (ys) treated between January 2009 and December 2011 were included. Demographics, comorbidity, treatment strategies and mortality were recorded. Results: Sixty-one patients were included (median age, 74.1 ys; range, 70-88; male, 74%; ECOG PS 0-1, 86.4%; stage IVA/IVB, 72%; recurrent disease, 11.5%). Forty-eight percent of subjects had ≥ 2 comorbidities (hypertension 51%; diabetes 21%; myocardial ischemia 15%; bronchopathy 33%, chronic renal insufficiency 25%, hepatopathy 5%). Primary tumor site was: oral cavity 34%; larynx 30%; oropharynx 23%; others 13%. Most of the aged (71%) were treated with radical concomitant BCRT (16% of them had received induction chemotherapy); 28% underwent surgery with adjuvant CRT. The schedules of BCRT were Cetuximab 38 (62.3%), triweekly Cisplatin 15 (24.6%) and others 8 (13.1%). The majority was able to complete all planned treatment (84% radiotherapy; 72% BCT). Complete and partial responses rates were 54% and 18% respectively. Number of comorbidities did not influence the election of BCRT. Nevertheless, ECOG PS ≥ 2 and age > 80 ys were related with cetuximab preference. There were 30 deaths: 21 from neoplasia, 1 from treatment complications (pneumonia). At 27 months' follow-up, 18 relapses and 6 second neoplasms were observed; 49% of the patients were alive (median overall survival 42 m). ACUTE TOXICITIES N % HEMATOLOGIC ≥ 3 6 9.8 MUCOSITIS ≥ 3 19 31.1 RASH ≥ 3 5 8.2 INFECTIONS 9 14.8 RENAL FAILURE 7 11.5 ADMISSION TO HOSPITAL 16 26.2 Conclusions: Elderly patients with LA-HNC benefit from radical multidisciplinary treatment. We still have to improve the rate of treatment compliance and reduce the toxicities, including a better election of BCRT schedule, taking into account comorbidities, PS and special needs (social, nutritional …) of this group of patients. Disclosure: All authors have declared no conflicts of interest.

Induction Docetaxel, Cisplatin, and 5-Fluorouracil Precludes Definitive Chemoradiotherapy in a Substantial Proportion of Patients With Head and Neck Cancer in a Low Socioeconomic Status Population

In this retrospective study we evaluate the tolerability and outcomes after induction chemotherapy for patients with predominately low socioeconomic status (SES) with locally advanced head and neck cancer (LAHNC). One hundred eighteen patients with LAHNC of the hypopharynx, larynx, oral cavity, or oropharynx began curative intent therapy with induction cisplatin (75 or 100 mg/m), docetaxel (75 mg/m), and 5-fluorouracil (750 mg/m×5 d or 1000 mg/m×4 d; continuous infusion) every 3 weeks (DPF) for a planned 2 to 3 cycles. All patients were to receive curative radiotherapy with concurrent systemic therapy. Associations were tested using χ test, and survival estimates were calculated using the Kaplan-Meier method. Most patients (75.4%) were of low SES. Induction DPF was delivered for a median of 2 cycles (range, 1 to 3) and 14% of the patients (n=17) died during induction DPF. After DPF, 38.2% of patients were unable to complete or receive planned definitive therapy. Overall 15.3% of patients died during therapy, and mortality was associated with a Karnofsky performance status <80 (P=0.04). At 2 years the locoregional control was 52.7%, whereas the distant metastases free rate was 72.6%, and the overall survival rate was 34.1%. Low SES patients were less likely to achieve locoregional control (P=0.05) or survive (P=0.08). In this population of LAHNC patients of low SES with a high tumor burden and poor performance status, use of induction DPF was associated with 15.3% mortality during therapy and precluded 38.2% of patients from initiating or completing planned definitive therapy.

Impact of initial FDG PET/CT in the management plan of patients with locally advanced head and neck cancer.

To determine the impact of initial FDG PET/CT staging on clinical stage and the management plan in patients with locally advanced head and neck cancer (LAHNC). We retrospectively reviewed the records of 72 consecutive patients (2007-2010) staged with PET/CT and conventional CT with tumours of hypopharynx/larynx (26 patients, 36%), oral cavity (17 patients, 24%), oropharynx (16 patients, 22%), nasopharynx (12 patients, 17%), and others (2%). The impact of PET/CT on management plans was considered high when PET/CT changed the planned treatment modality or treatment intent, and intramodality changes were considered as minor changes with low impact. FDG PET/CT changed the stage in 27 patients and had high impact on the management plan in 12% of patients (detection of distant metastases in 6 patients and stage II in 2 patients). Intramodality changes were more frequent: FDG PET/CT altered the TNM stage in 18/72 (25%) of patients, upstaging N stage in 90% of patients with low impact. Initial FDG PET/CT staging not only improves stage but also affects the management plan in LAHNC patients.

Degree of nephrotoxicity after intermediate or high-dose cisplatin-based chemoradiotherapy (CRT) in patients with locally advanced head and neck cancer (LAHNC).

6056 Background: CRT with cisplatin 100 mg/m2 on days 1, 22, 43 (cis100) is standard treatment for LAHNC and nasopharyngeal cancers (NPC) patients (pts). An alternative CRT schedule consists of cisplatin 40 mg/m2 weekly during six weeks (cis40). A direct prospective comparison of these 2 schedules has not been performed, yet. Data on the influence of these schedules on cisplatin-based nephrotoxicity are scarce. This study compared the occurrence of cisplatin-induced nephrotoxicity between these 2 CRT schedules. Methods: All pts treated with CRT for LAHNC or NPC from 2003 until 2011 in the Radboud university medical center were studied retrospectively. One hundred forty-four LAHNC/NPC pts were included, of whom 40 received cis100 and 104 received cis40. Serum creatinine at baseline and maximal rise during treatment were collected. An increase of 25% was established as clinically relevant. Nephrotoxicity was scored according to both the CTCAE version 3.0 and version 4.03. Results: Baseline serum creatinine ...

Concurrent Cisplatin and Radiation Versus Cetuximab and Radiation for Locally Advanced Head-and-Neck Cancer

To compare concurrent cisplatin (CDDP) and radiation (RT) with cetuximab (C225) and RT for locally advanced head-and-neck cancer (LAHNC). This study retrospectively compared 174 consecutive, newly diagnosed LAHNC patients definitively treated from March 1, 2006, to April 1, 2008, with single-agent CDDP/RT (n = 125) or C225/RT (n = 49). We excluded patients who received additional concurrent, induction, or adjuvant systemic therapy; weekly cisplatin; prior head-and-neck radiotherapy; or primary surgical resection. Outcomes were analyzed by the Kaplan-Meier method, Cox model, and competing-risks analysis tools. The C225/RT patients were older and had decreased creatinine clearance. At a median follow-up of 22.5 months for living patients, the 2-year locoregional failure rate was 5.7% for CDDP/RT and 39.9% for C225/RT (p < 0.0001). The 2-year failure-free survival (FFS) and overall survival (OS) rates were 87.4% vs. 44.5% (p < 0.0001) and 92.8% vs. 66.6% (p = 0.0003), respectively, in favor of CDDP/RT. When the Cox proportional hazards model was used for multivariate analysis, treatment with CDDP/RT predicted for improved locoregional control (p < 0.0001), FFS (p < 0.0001), and OS (p = 0.01). Late Grade 3 or 4 toxicity or feeding tube dependence 9 months after completion of RT was observed in 21% of patients in the CDDP/RT cohort and 24% in the C225/RT cohort (p=0.66). In this study of LAHNC patients, CDDP/RT achieved better locoregional control, FFS, and OS than C225/RT. Although the results were upheld on multivariate analysis, they must be interpreted cautiously because of the retrospective nature of the study and significant differences in patient selection. There was no statistically significant difference in late Grade 3 or 4 effects or feeding tube dependence.

S165 – Locally Advanced Head and Neck Cancer Treatment Patterns

Objectives We assessed the extent of chemoradiation therapy (CRT) or high-dose platinum-based chemotherapy plus radiation (P-CRT) initiation for patients with stage III/IV, locally advanced head and neck cancer (LAHNC) treated in the VA New England Healthcare System (VA-NEHS), and identified the factors associated with such initiation. Methods Newly diagnosed LAHNC patients treated in the VA-NEHS (from 1996 to 2006) were identified from electronic records. Patients’ tumor staging (TNM), demographics, performance score, comorbidities, alcohol and tobacco use or dependence, and diagnosis year were abstracted via chart review. The primary outcome was the initial treatment strategy, grouped as CRT ± surgery (including P-CRT), chemotherapy (CT) ± surgery, radiation therapy (RT) ± surgery, surgery alone, or no treatment. Multiple logistic regressions compared odds of failure to initiate CRT or P-CRT across the aforementioned patient characteristics. Results Of 496 patients identified, 34.5%, 34.7%, 6.7%, and 5.4% initiated CRT, RT, CT, and surgery alone, respectively, whereas 18.8% were untreated. Most patients initiating CRT (59.7%) or CT (51.5%) received platinum-based chemotherapy. Predictors of failure to initiate CRT included diagnosis year 2002 (OR=3.57, 95% CI: 2.32, 5.55), age &gt;65 years old (OR=2.47, 95% CI: 1.55, 3.92), performance score &lt;90 (OR=2.27, 95% CI: 1.43, 3.59), and past/present alcohol use (OR=1.95, 95% CI: 1.08, 3.52). Similar factors predicted failure to initiate P-CRT. Conclusions Although CRT/P-CRT initiation increased over time, older patients, patients with poorer performance status, and those using alcohol were less likely to initiate CRT. Research is needed to describe treatment outcomes in LAHNC patients not initiating CRT/P-CRT.

Intensity-Modulated Radiation Therapy (IMRT) With Concurrent Taxane-Based Chemotherapy for Locally-Advanced Head and Neck Cancer (LAHNC): Toxicities and Efficacy

The addition of chemotherapy to radiotherapy improves survival in LAHNC at the expense of higher toxicity. IMRT for LAHNC provides a means to minimize dose to normal tissue. Our experience with concurrent IMRT and taxane-based chemotherapy in 128 sequential LAHNC patients is presented.