Locally Advanced Head And Neck Cancer Research Articles

A comparative analysis between sequential boost and integrated boost intensity-modulated radiation therapy with concurrent chemotherapy for locally-advanced head and neck cancer

BackgroundPlanning and delivery of IMRT for locally advanced head and neck cancer (LAHNC) can be performed using sequential boost or simultaneous integrated boost (SIB). Whether these techniques differ in treatment-related outcomes including survival and acute and late toxicities remain largely unexplored.MethodsWe performed a single institutional retrospective matched cohort analysis on patients with LAHNC treated with definitive chemoradiotherapy to 69.3 Gy in 33 fractions. Treatment was delivered via sequential boost (n = 68) or SIB (n = 141). Contours, plan evaluation, and toxicity assessment were performed by a single experienced physician. Toxicities were graded weekly during treatment and at 3-month follow up intervals. Recurrence-free survival, disease-free survival, and overall survival were estimated via Kaplan-Meier statistical method.ResultsAt 4 years, the estimated overall survival was 69.3% in the sequential boost cohort and 76.8% in the SIB cohort (p = 0.13). Disease-free survival was 63 and 69% respectively (p = 0.27). There were no significant differences in local, regional or distant recurrence-free survival. There were no significant differences in weight loss (p = 0.291), gastrostomy tube placement (p = 0.494), or duration of gastrostomy tube dependence (p = 0.465). Rates of acute grade 3 or 4 dysphagia (82% vs 55%) and dermatitis (78% vs 58%) were significantly higher in the SIB group (p < 0.001 and p = 0.012 respectively). Moreover, a greater percentage of the SIB cohort did not receive the prescribed dose due to acute toxicity (7% versus 0, p = 0.028).ConclusionsThere were no differences in disease related outcomes between the two treatment delivery approaches. A higher rate of grade 3 and 4 radiation dermatitis and dysphagia were observed in the SIB group, however this did not translate into differences in late toxicity. Additional investigation is necessary to further evaluate the acute toxicity differences.

989P - Ototoxicity in locally advanced head and neck cancer (LAHNC) patients (pts) treated with induction chemotherapy (IC) followed by cisplatin-based chemoradiotherapy (CRT)

989P - Ototoxicity in locally advanced head and neck cancer (LAHNC) patients (pts) treated with induction chemotherapy (IC) followed by cisplatin-based chemoradiotherapy (CRT)

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.

Retrospective comparison between high-dose cisplatin and less-intensive weekly cisplatin/paclitaxel concurrently with radiation for locally advanced head and neck cancer (LAHNC).

e17535Background: Concurrent high dose Cisplatin (q3 weekly) or Cetuximab with radiation have shown improvement in survival for LAHNC compared to radiation alone. No randomized study has compared C...

Sequential boost versus integrated boost intensity-modulated radiation therapy with concurrent chemotherapy for locally-advanced head and neck cancer (LAHNC).

6070Background: Despite IMRT technological advances, toxicity in LAHNC pts remains extreme. Different IMRT techniques have been developed, including sequential boost (SeqB) and simultaneous integra...

Tumour volumes: Predictors of early treatment response in locally advanced head and neck cancers treated with definitive chemoradiation

AimTo analyse and predict early response 3 months post definitive chemoradiation (CCRT) utilising tumour volume (TV) measurement in locally advanced head and neck cancers (LAHNC). BackgroundLAHNC are 3-dimentional lesions. The largest diameter of these tumours measured for T-classification may not necessarily reflect the true tumour dimensions. TV accurately reflects the tumour burden because it is a measurement of tumour burden in all three dimensions. Materials and methodsIt is a single institutional prospective study including 101 patients with LAHNC treated with definitive CCRT. TV data noted were primary tumour volume (PTV), total nodal volume (TNV) and total tumour volume (TTV). Response evaluation was done at 3 months after the completion of definitive CCRT and patients were categorised either having achieved complete response (CR) or residual disease. ResultsPatients who had not achieved CR were found to have larger TV compared with those who had achieved CR. There were significant inverse correlations between PTV and response (median 16.37cm3 vs. 45.2cm3; p=0.001), and between TTV and response (median 36.14cm3 vs. 66.06cm3; p<0.001). Receiver operating characteristic (ROC) analysis identified an “optimal cut-off” value of 41cm3 for PTV and 42cm3 for TTV above and below which the magnitude of difference in response was the greatest. ConclusionsIf response evaluation 3 months post CCRT is to be predicted it is simply not enough to measure the largest single dimension of the tumour. TV seems to be a better and more accurate reflection of the true total tumour burden or extent of the disease.

Impact of Adaptive Radiotherapy on Locally Advanced Head and Neck Cancer - A Dosimetric and Volumetric Study.

Objective of the study is to evaluate volumetric and dosimetric alterations taking place during radiotherapy for locally advanced head and neck cancer (LAHNC) and to assess benefit of replanning in them. Thirty patients with LAHNC fulfilling the inclusion and exclusion criteria were enrolled in a prospective study. Planning scans were acquired both pre-treatment and after 20 fractions (mid-course) of radiotherapy. Single plan (OPLAN) based on initial CT scan was generated and executed for entire treatment course. Beam configuration of OPLAN was applied to anatomy of interim scan and a hybrid plan (HPLAN30) was generated. Adaptive replanning (RPLAN30) for remaining fractions was done and dose distribution with and without replanning compared for remaining fractions. Substantial shrinkage of target volume (TV) and parotids after 4 weeks of radiotherapy was reported (p<0.05). No significant difference between planned and delivered doses was seen for remaining fractions. Hybrid plans showed increase in delivered dose to spinal cord and parotids for remaining fractions. Interim replanning improved homogeneity of treatment plan and significantly reduced doses to cord (Dmax, D2% and D1%) and ipsilateral parotid (D33%, D50% and D66%) (p<0.05). Use of one or two mid-treatment CT scans and replanning provides greater normal tissue sparing alongwith improved TV coverage.

E1 detection as prognosticator in human papillomavirus-positive head and neck cancers.

HPV-related locally advanced head and neck cancers (LA-HNCs) show a good prognosis. This study aimed to investigate the HPV prevalence in LA-HNCs and compare the prognostic value of E1, E6 and L1 genomic viral fragments and p16, individually and in combination, in order to find the best prognosticator in terms of overall survival (OS) and progression-free survival (PFS). HPV16 was searched in 255 LA-HNC formalin-fixed paraffin-embedded tumor tissues, 89 oropharyngeal cancers (OPCs), and 166 non-OPCs by DNA-PCR with 3 primer pairs. p16 was analyzed by immunohistochemistry in 235 patients. The prevalence of positive samples decreased constantly from E6 to L1 and E1 in both OPCs and non-OPCs. Each LA-HNC patient highlighted variable positivity for each fragment. OPCs showed a higher prevalence of positive samples compared to non-OPCs.Positive coexistence of all the fragments was more common in OPCs (31.5%) than non-OPCs (4.2%), and E1 detection was always associated with E6 and L1. E1-positive OPCs showed improved OS (p = 0.012) and PFS (p = 0.036), while L1- or E6-positive ones did not. p16-positive patients were more prevalent in the OPC (29.8%) than the non-OPC group (7.3%) (p&lt;0.0001) and its prognostic value was not superior to that of E1. However, the multivariate Cox analysis which included E1, L1, E6 status and p16 expression did not show a significant p value. Though HPV16 positivity measured by DNA-PCR was higher for L1 and E6, they performed weakly as prognosticators; E1 might become a strong prognostic marker for OS and PFS in OPCs.

A Prospective Randomized Study Evaluating the Role of Oral Curcumin along with Chemoradiationin Management of Locally Advanced Head and Neck Carcinoma

Aim: This study was to evaluate the role of Curcumin along with or without chemoradiation in the management of locally advanced head and neck cancers (LHNC) in terms of tolerability, toxicity and response. Sixty treatment naive histopathologically proved cases LHNC were included in this prospective randomized study. Materials and Methods: Patients were randomly assigned to receive radical external beam radiotherapy (EBRT) with weekly cisplatin and capsule Curcumin from the first day of EBRT till the Original Research Article Kumar et al.; IJTDH, 16(1): 1-7, 2016; Article no.IJTDH.25780 2 completion in the dose of 1gm every 8 hourly (Group I/Study Group) and EBRT with weekly cisplatin only (Group II/Control Group). Results: There were lower grades of statistically insignificant haemoglobin (grade 2 p value0.300) and total leucocyte count (grade 1 p value0.313), toxicities in group II in compared to group I during treatment. The acute skin and mucosal reactions were less in group I than group II without any statistically significant association during treatment and follow ups. Statistically significant less blood urea (grade 1 p value0.019) toxicities observed in group I, in compared to group II during treatment. There were statistically significant fewer grade 3 and 4 vomiting (p value0.037) in group II. At one year follow up 67% was disease free in group I in comparison to 56% in group II. Conclusion: Curcumin, in management of LHNC, seems to decreases haematological, renal, skin and mucosal chemoradiation induced toxicities results in timely completion of intended treatment without any financial burden on patients and improves the disease control.

Gemcitabine-Based Chemoradiation in the Treatment of Locally Advanced Head and Neck Cancer: Systematic Review of Literature and Meta-Analysis.

Platinum-based concurrent chemoradiation (CCRT) improves locoregional control and overall survival of locoregionally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN) when compared to radiotherapy alone, but this approach is hampered by significant toxicity. Therefore, alternative ways to enhance the radiation effects are worth investigating. Gemcitabine (2',2'-difluorodeoxycytidine), in addition to its activity against a variety of solid tumors, including SCCHN, is one of the most potent radiosensitizers, and it has an overall favorable safety profile. In this paper, the clinical experience with gemcitabine-based chemoradiation in the treatment of patients with LA-SCCHN is reviewed. We conducted a review of the literature on the clinical experience with radiotherapy combined with either single-agent gemcitabine or gemcitabine/cisplatin-based polychemotherapy for the treatment of patients with LA-SCCHN. We also searched abstracts in databases of major international oncology meetings from the last 20 years. A meta-analysis was performed to calculate pooled proportions with 95% confidence intervals (CIs) for complete response rate and grade 3-4 acute mucositis rate. A total of 13 papers were eligible for the literature review. For schedules using a gemcitabine dose intensity (DI) below 50 mg/m(2) per week, the complete response rate was 86% (95% CI, 74%-93%) with grade 3-4 acute mucositis rate of 38% (95% CI, 27%-50%) and acceptable late toxicity. In one of the studies employing such low DIs, survival data were provided showing a 3-year overall survival of 50%. Compared with DI ≥50 mg/m(2) per week, there was no difference in the complete response rate (71%; 95% CI, 55%-83%; p = .087) but a significantly higher (p < .001) grade 3-4 acute mucositis rate of 74% (95% CI, 62%-83%), often leading to treatment interruptions (survival data provided in 8 studies; 3-year overall survival, 27%-63%). Late toxicity comprising mainly dysphagia was generally underreported, whereas information about xerostomia and skin fibrosis was scarce. This review highlights the radiosensitizing potential of gemcitabine and suggests that even very low dosages (less than 50 mg/m(2) per week) provide a sufficient therapeutic ratio and therefore should be further investigated. Refinements in radiation schemes, including intensity-modulated radiation therapy, in combination with low-dose gemcitabine and targeted agents, such as cetuximab, are currently being investigated. Cisplatin-based concurrent chemoradiation (CCRT) has become the standard treatment of locally advanced head and neck cancer (LAHNC). This approach is hampered by significant toxicity. This paper reviews the studies using gemcitabine as an alternative radio-sensitizer for CCRT in patients with LAHNC. In this capacity, despite its mild intrinsic toxicity, gemcitabine comes with high rates of severe mucositis when used in dosages exceeding 50 mg/m(2) per week. CCRT with low-dose gemcitabine provides a sufficient therapeutic ratio, combining clinical activity, similar to the higher-dose regimens, with lower toxicity. Further investigation is warranted.

318P Induction chemotherapy followed by concurrent chemoradiation (CCRT) in unresectable locally advanced head and neck cancer (LAHNC)

318P Induction chemotherapy followed by concurrent chemoradiation (CCRT) in unresectable locally advanced head and neck cancer (LAHNC)

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.

G01* - The phase III study INTERCEPTOR in locally advanced head and neck cancer (LA-HNC). Preliminary safety report

G01* - The phase III study INTERCEPTOR in locally advanced head and neck cancer (LA-HNC). Preliminary safety report

2821 The phase III study INTERCEPTOR in locally advanced head and neck cancer (LA-HNC). Preliminary safety report

2821 The phase III study INTERCEPTOR in locally advanced head and neck cancer (LA-HNC). Preliminary safety report

P0013 Role of adaptive radiotherapy in locally advanced head and neck cancer: A dosimetric analysis

Background This study aimed to evaluate the dosimetric effect of anatomical and volumetric changes in tumour size on target volumes (TVs) and organ at risks (OARs) during intensity-modulated radiotherapy (IMRT), and to compare the dose distribution with or without replanning in locally advanced head and neck cancer (LAHNC). Methods 20 patients with LAHNC treated by IMRT were enrolled in a prospective study. Planning computed tomography (CT) scans were acquired both pre-treatment and after 20 fractions (midcourse) of radiotherapy. An original treatment plan based on initial planning CT scan was generated and implemented. A hybrid plan was generated for each patient by applying beam configuration of the original plan to the anatomy of the midcourse CT scan. The dose-volume histograms of the original plan and hybrid plan were compared for second phase of treatment. A midcourse adaptive replan based on the interim CT scan was done, and dose distribution for TVs and OARs was compared with or without replanning. Findings Planned doses (D98%, D95%, and D2%) to TVs for second phase of radiotherapy (hybrid plan) were not significantly different from the actually delivered doses. However, an increase in volume by 110% was observed in the HPLAN in comparison with the original plan. With replanning, dose distribution to TV was made more homogenous as compared with the hybrid plan (p = 0.00). Re-planning significantly reduced V > 110% and V Interpretation Replanning with midcourse CT simulation significantly improves the TV coverage and reduces the dose to OARs.

Prognostic value of HPV detection with three primer sets in 255 Head-Neck cancers.

6045 Background: HPV-related patients (pts) with locally advanced head and neck cancers (LA-HNCs) have a better prognosis than the HPV-negative ones. This study aimed to investigate the prevalence ...

Is there a role for induction chemotherapy in the setting of concomitant chemoradiation in locally advanced head and neck cancer: A systematic review and meta-analysis of randomized controlled trials.

6068 Background: :There is a controversy regarding the role of induction chemotherapy (IC) prior to concomitant chemoradiation (CCRT) in locally advanced head and neck cancer (LAHNC). We performed ...

Effects of EGFR, CK19, CK20 and Survinin gene expression on radiotherapy results in patients with locally advanced head and neck cancer.

To investigate the effects of epidermal growth factor receptor (EGFR), cytokeratin 19 (CK19), cytokeratin 20 (CK20) and survinin gene expression on local control (LC) and overall survival (OS) in patients with locally advanced head and neck cancer (LAHNC) who were administered radiotherapy (RT). Twenty-six patients who were admitted to Uludag University Medical Faculty Department of Radiation Oncology with a diagnosis of LAHNC (GIII-GIV) were included in this study. Gene expression was evaluated in tumor tissues and peripheral blood. RNA isolation was performed on paraffinized tumor tissues and peripheral blood samples obtained before RT (BR). The densities of the obtained RNAs were analyzed at 260/280 nm. cDNA samples obtained from total RNA,EGFR, CK19, CK20 and survinin gene expression levels were assessed via the Sybr Green method and data were analyzed with the ΔΔCt method. The same process was repeated for peripheral blood samples taken after RT (AR). The female/male ratio was 3:23 and the mean age was 56.5 years (38-75 years). After radiotherapy, CK19 and CK20 levels in the peripheral blood were found to be correlated according to Pearson correlation analysis(p=0.049). This result indicates a possibility of remaining positive for CK19 and CK20 in the peripheral blood even after RT in patients with CK19, CK20, and EGFR positive tumors before RT. There was a statistically significant correlation between survinin levels measured BR and AR (p=0.028). In this study, we found that patients with any EGFR, CK19, CK20 or survinin positivity in their peripheral blood obtain less benefit from radiotherapy. A wider patient population and advanced protein analyses are necessary in order to increase the reliability of our findings.

Impact of head and neck cancer adaptive radiotherapy to spare the parotid glands and decrease the risk of xerostomia.

BackgroundLarge anatomical variations occur during the course of intensity-modulated radiation therapy (IMRT) for locally advanced head and neck cancer (LAHNC). The risks are therefore a parotid glands (PG) overdose and a xerostomia increase.The purposes of the study were to estimate:- the PG overdose and the xerostomia risk increase during a “standard” IMRT (IMRTstd);- the benefits of an adaptive IMRT (ART) with weekly replanning to spare the PGs and limit the risk of xerostomia.Material and methodsFifteen patients received radical IMRT (70 Gy) for LAHNC. Weekly CTs were used to estimate the dose distributions delivered during the treatment, corresponding either to the initial planning (IMRTstd) or to weekly replanning (ART). PGs dose were recalculated at the fraction, from the weekly CTs. PG cumulated doses were then estimated using deformable image registration. The following PG doses were compared: pre-treatment planned dose, per-treatment IMRTstd and ART. The corresponding estimated risks of xerostomia were also compared. Correlations between anatomical markers and dose differences were searched.ResultsCompared to the initial planning, a PG overdose was observed during IMRTstd for 59% of the PGs, with an average increase of 3.7 Gy (10.0 Gy maximum) for the mean dose, and of 8.2% (23.9% maximum) for the risk of xerostomia. Compared to the initial planning, weekly replanning reduced the PG mean dose for all the patients (p < 0.05). In the overirradiated PG group, weekly replanning reduced the mean dose by 5.1 Gy (12.2 Gy maximum) and the absolute risk of xerostomia by 11% (p < 0.01) (30% maximum). The PG overdose and the dosimetric benefit of replanning increased with the tumor shrinkage and the neck thickness reduction (p < 0.001).ConclusionDuring the course of LAHNC IMRT, around 60% of the PGs are overdosed of 4 Gy. Weekly replanning decreased the PG mean dose by 5 Gy, and therefore by 11% the xerostomia risk.

Cisplatin, cetuximab, and radiation in locally advanced head and neck squamous cell cancer: a retrospective review.

Efficacy of cisplatin versus cetuximab with radiation in locally advanced head and neck cancer (LAHNC) was evaluated. A total of 96 patients with newly diagnosed LAHNC treated at our institution between 2006 and 2011 with concurrent radiation and cisplatin (group A, n = 45), cetuximab (group B, n = 24), or started with cisplatin but switched to cetuximab because of toxicity (group C, n = 27) were reviewed. Chi-square test, analysis of variance, and log-rank test were used for analysis. The three groups had similar baseline characteristics, except for median age, T stage, albumin levels, hemoglobin levels, performance status, and comorbidities. A complete response (CR) was seen in 77%, 17%, and 67% of patients (P < 0.001), respectively. There was no significant difference in median overall survival (OS) between groups A and C. The median OS for groups A and C was not reached (>65 months), even though it was significantly longer than median OS for group B (11.6 months; P ≤ 0.001). The 2-year OS in groups A and C is significantly higher than that in group B (70% for groups A and C, 22% for group B). There is no significant difference in progression-free survival (PFS) between groups A and C. The median PFS for these groups was not reached (>62 months), and is significantly longer than that for group B (4.3 months; P ≤ 0.001). The 2-year PFS of group A (67%) and group C (76%) was significantly longer than that of group B (20%). Cisplatin with radiation appears to be more efficacious even in suboptimal dosing than cetuximab with radiation in LAHNC but the two groups were not well matched.