Locally Advanced Head And Neck Carcinoma Research Articles

879P Adaptive radiotherapy in head and neck cancer: A prospective dosimetric and volumetric study

Adaptive replanning leads to decrease dose to normal tissues and improves the target volume coverage. We conducted this study to determine the volumetric and dosimetric changes during the treatment course and observe the optimum timing of replanning in locally advanced head and neck carcinoma (LAHNC).

Randomized trial on acute toxicities of weekly vs three-weekly cisplatin-based chemoradiation in head and neck cancer.

BackgroundThe current first‐line treatment of locally advanced head and neck carcinoma (LAHNC) is concurrent chemoradiation with three‐weekly cisplatin 100 mg/m2. However, prescribing cisplatin at this dose increases the treatment toxicity, which may compromise the treatment results. An alternative schedule is weekly 40 mg/m2 cisplatin.AimTo compare the acute hematologic and renal toxicities of these two regimens.MethodsThis randomized clinical trial included 77 LAHNC patients who were allocated to a high dose (100 mg/m2 every 3 weeks) or low dose (40 mg/m2 weekly) cisplatin group concurrent with radiotherapy. Hematologic and renal indices were measured weekly during chemoradiation.ResultsThe average age of patients was 55.3 years. Overall, 71.4% of patients were treated in a definitive setting. The incidence of severe hematologic events was not significantly different. However, the average estimated glomerular filtration rate (eGFR) was significantly greater in the three‐weekly group (67.85 vs. 58.57% mL/min per 1.73 m2; P‐value = .02). Cumulative cisplatin dose of ≥240 mg/m2 was significantly greater in the weekly group. Totally, treatment breaks occurred in 40.3% of patients due to treatment toxicity. Treatment interruption was primarily due to neutropenia in the three‐weekly and renal dysfunction and thrombocytopenia in the weekly group.ConclusionsSevere acute hematologic toxicities were comparable for three‐weekly and weekly groups. The decrease in eGFR through treatment was more significant with weekly cisplatin. Further follow‐up, however, is needed to confirm its impact on delayed renal function.

Health-related quality of life of patients treated with chemoradiotherapy plus or minus prophylactic antibiotics to reduce the number of pneumonias for locally advanced head and neck cancer, the PANTAP study

ObjectivesThe recent PANTAP trial showed that administration of prophylactic antibiotics in locally advanced head and neck carcinoma (LAHNC) patients treated with chemoradiotherapy reduced fever, hospitalization and costs. The current study describes the effect of prophylactic antibiotics on health-related quality of life (HRQoL), another secondary endpoint of the trial. Materials and methodsIn this multicenter randomized trial, LAHNC patients treated with chemoradiotherapy received prophylactic antibiotics or standard care. HRQoL was assessed at baseline (before chemoradiotherapy), day 28 of chemoradiotherapy (one day before starting prophylactic antibiotics), the final day of radiotherapy, and 3.5 months after the end of chemoradiotherapy, using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, EORTC H&N35 module, and the Performance Status Scale for Head & Neck cancer patients (PSS-HN). ResultsNinety-five patients were randomized: 48 patients were allocated to the standard group and 47 patients to the prophylaxis group. Thirty-four patients in the standard group (70.8%) and 28 patients in the prophylaxis group (59.6%) completed the questionnaires at baseline and at follow-up. No significant differences in HRQoL were found at baseline and at day 28. At the end of radiotherapy, the prophylaxis group performed better on almost all functional subscales of the EORTC QLQ-C30 and reported less symptoms. At the end of follow up, almost no differences were seen between the two treatment groups. ConclusionProphylactic antibiotics during chemoradiotherapy for LAHNC patients improved HRQoL at the end of the radiotherapy, however no differences were found 3.5 months after the end of chemoradiotherapy.

Definitive Radiotherapy Combined with Targeted Therapy in Locoregional Advanced Cancer of Larynx, Hypopharynx and Oropharynx-preliminary Report of Single Institution Experience, Patients Compliance to the Treatment Protocol and Early Toxicity

Objective: To report the clinical experience of Radiotherapy Department at University Hospital St. Marina, Varna, with definitive radiotherapy combined with targeted therapy Cetuximab in patients with locally advanced head and neck carcinoma (LAHNC), the observed toxicity and management protocol. Materials and Methods: The study included 36 patients with LAHNC who received definitive radiotherapy combined with Cetuximab in the period 2015-2018., VMAT and IGRT irradiation techniques were applied in all patients, with a prescription of total dose to 70Gy in the primary tumor and the involved lymph nodes, based on PET-CT. Cetuximab was administered according to the known protocol. Both Radiotheray and Medical Oncology Departments of the University Hospital “St. Marina” – Varna elaborated common protocol for premedication. The side effects were evaluated by the treating physician according to the CTCAE vers. 4.0. Results: During the application of the loading dose, an anaphylactic reaction was observed in 6 out of all 36 patients. The reduction of maintenance doses with 75% was done only in two patients without interruption of radiotherapy schedule and the planned infusions. One patient refuses to continue therapy. One patient died of cardiac comorbidity in the second week. All the others 26 patients completed the full course radiotherapy combined with full dose target therapy, with only moderate toxicity up to grade 3. No haematological toxicity was observed. Conclusion: The reported patients compliance was high 75%, with no higher than grade 3 side effects and a good quality of life. To our knowledge currently, this is the first study in Bulgarian clinical practice regarding the application of Cetuximab in combination with radiation therapy and reporting of early toxicity and patients compliance.

Comparative Evaluation of Palliative Radiotherapy with Chemotherapy vs. Palliative Radiotherapy Alone in Locally Advanced Head and Neck Cancer

Background: The aim of the study was to evaluate and compare the efficacy, tolerability and toxicity of two palliative radiotherapy (RT) schedules in locally advanced head and neck carcinoma (LAHNC), i.e., Quad Shot schedule with chemotherapy and Quad Shot schedule alone. Methods: The patients were randomly divided into two groups of 30 each. Group I patients were planned for 14.8 Gy in 4 fractions over 2 days every 3 weeks for three cycles. All these patients also received paclitaxel 60 mg/m2 intravenous. Group II patients received 14.8 Gy in 4 fractions over 2 days every 3 weeks for three cycles alone. All these patients in Group I and II received total radiation dose of 44.4 Gy. Results: At the end of treatment, complete tumor response (CR) in Group I was better than Group II (40% vs. 36.7%). Disease status (tumor+node) at the end of treatment in terms of complete response was 36.7% vs. 0% (11/30 and 0/30) in Group I and II. Disease status at 6 months of follow up was noted as follows: complete tumor response in Group I and II was 23.3% (7/30) vs. 10% (3/30) (p=0.012). Complete nodal response was 35.7% (10/28) in Group I and 6.67% (02/30) in Group II (p= 0.538). Overall, no evidence of disease was observed in 16.7% (5/30) in Group I and 3.3% (1/30) in Group II respectively (p<0.001). Conclusion: This palliative schedule has been shown to provide good tumor response and palliation of symptoms. The toxicity profile remains low with the addition of paclitaxel. Further investigation is warranted in a larger trial. Palliation of symptoms resulted in improved quality of life for these group of patients

Cost-effectiveness of prophylactic antibiotics to prevent pneumonia in patients treated with chemoradiotherapy (CRT) for locally advanced head and neck carcinoma (LAHNC).

6075 Background: Recently, we reported about a prospective randomized study (PANTAP-study) investigating the effect of prophylactic antibiotics in LAHNC pts treated with CRT. We did not show a reduction in pneumonias, but did find a significant decrease in the number of hospitalizations. Detailed quality of life (QoL) results have been reported elsewhere. Now we present the results of the cost-effectiveness analysis. Methods: A multicenter study was performed in LAHNC pts treated with CRT, i.e.cisplatin weekly or 3-weekly combined with radiotherapy for 42 or 49 days. The standard treatment group (STG) received no prophylactic antibiotics; the intervention group (IG) received prophylactic antibiotics, i.e. amoxicillin/clavulanic acid, from day 29 until 14 days after completion of CRT. QoL questionnaires, including EQ-5D, QLQ-C30, EORTC Head&amp;Neck35 and PSSHN, were taken before start of CRT, before start of antibiotics, at the end of CRT and at the end of follow up. Costs of hospitalization, prophylactic antibiotics, pain medication and anti-emetics were taken into account for the cost-effectiveness analysis. Results: A total of 94 pts were randomized; 48 pts to the STG and 47 pts to the IG. Between the STG and IG we found a difference per patient in costs of hospitalization of €2076 and €682 (p = 0.03), respectively, but not in the costs for pain medication per patient €78 and €46, respectively, (p = 0.382). The total costs of hospitalization in combination with prophylactic antibiotics, pain medication and anti-emetics were €2462 and €1037 (p = 0.046) in the STG and IG respectively, leading to a difference in total costs per patient of €1425 in favor of the IG. There were no significant differences in QoL between the groups. Conclusions: Prophylactic antibiotics during CRT for LAHNC did not reduce the rate of pneumonias, but reduced the number of hospitalizations in the IG, which led to a significant reduction in costs. Given the lack of adverse clinical effects, the same QoL, the cost savings and the impact of costs of hospitalization on health care globally, we recommend the use of prophylactic antibiotics in LAHNC pts receiving CRT. Clinical trial information: NCT01598402.

Retrospective evaluation of concomitant cetuximab and radiotherapy tolerance for locoregional advanced head and neck squamous cell carcinoma treatment in patients unfit for platinum-based chemotherapy.

Radiotherapy associated with cetuximab (Cet-RT) is an alternative treatment to platinum-based chemoradiotherapy in locally advanced head and neck carcinoma (LAHNC). Reviews suggest that the use of cetuximab is associated with poorer tolerance in patients unfit for chemotherapy than in pivotal trial. We retrospectively studied patients first treated by Cet-RT for LAHNC presenting contraindications to chemoradiotherapy. Objectives were treated population description, acute tolerance, progression-free survival (PFS), overall survival (OS), and 3-month clinical response. Eighty-eight patients were included. Treatment was completed without delay for 43 patients. Grade 3-4 acute toxicity was described in 44.3%: mucositis (n = 20), radiodermatitis (n = 25) folliculitis (n = 10), and anaphylaxis (n = 6). Fourteen patients died during treatment. Median PFS and OS were 6.3 and 18.7 months, respectively. We confirm that Cet-RT tolerance in unfit patients is poorer than that in trials. Survival data illustrate patients' frailty and suggest that balanced use of Cet-RT is required in this population.

Comparative Evaluation of Three Palliative Radiotherapy Schedules in Locally Advanced Head and Neck Cancer.

BackgroundThe aim of the study was to evaluate and compare the efficacy, tolerability and toxicity of three palliative radiotherapy (RT) schedules in locally advanced head and neck carcinoma (LAHNC), i.e. Quad Shot schedule, Christie schedule and conventional palliative schedule.MethodsThe patients were randomly divided into three groups of 30 each. Group I patients were planned for 14.8 Gy in 4 fractions over 2 days, repeated three weekly for two more cycles. Group II patients were planned for 50 Gy in 16 fractions over 3.1 weeks. Group III patients were planned for 20 Gy in 5 fractions over 5 days, repeated after an interval of 3 weeks. The quality of life was assessed before and after RT using University of Washington Quality of Life questionnaire version 4.ResultsLocal control rates were 84%, 76%, and 76% for groups I, II and III, respectively. Disease status at 6-month follow-up was no evidence of disease (20%, 28%, and 16%), residual disease (72%, 48%, and 76%), and recurrent disease (8%, 24%, and 8%) in groups I, II and III, respectively. Grade III acute skin reactions were 28%, 44%, and 16% in groups I, II and III, respectively. Grade III acute mucosal reactions were 36%, 56%, and 24% in group I, II and III, respectively. Quality of life improved in all groups after RT.ConclusionQuad Shot schedule may be used in LAHNC with better local control and acceptable toxicity as compared to conventional palliative RT schedule in Indian setting.

A Nomogram to predict parotid gland overdose in head and neck IMRT.

PurposesTo generate a nomogram to predict parotid gland (PG) overdose and to quantify the dosimetric benefit of weekly replanning based on its findings, in the context of intensity-modulated radiotherapy (IMRT) for locally-advanced head and neck carcinoma (LAHNC).Material and methodsTwenty LAHNC patients treated with radical IMRT underwent weekly computed tomography (CT) scans during IMRT. The cumulated PG dose was estimated by elastic registration. Early predictors of PG overdose (cumulated minus planned doses) were identified, enabling a nomogram to be generated from a linear regression model. Its performance was evaluated using a leave-one-out method. The benefit of weekly replanning was then estimated for the nomogram-identified PG overdose patients.ResultsClinical target volume 70 (CTV70) and the mean PG dose calculated from the planning and first weekly CTs were early predictors of PG overdose, enabling a nomogram to be generated. A mean PG overdose of 2.5Gy was calculated for 16 patients, 14 identified by the nomogram. All patients with PG overdoses >1.5Gy were identified. Compared to the cumulated delivered dose, weekly replanning of these 14 targeted patients enabled a 3.3Gy decrease in the mean PG dose.ConclusionBased on the planning and first week CTs, our nomogram allowed the identification of all patients with PG overdoses >2.5Gy to be identified, who then benefitted from a final 4Gy decrease in mean PG overdose by means of weekly replanning.

Prophylactic antibiotics to prevent pneumonia in patients treated with chemoradiotherapy (CRT) for locally advanced head and neck carcinoma (LAHNC).

6079Background: Platinum-based CRT is the treatment of choice for LAHNC, but induces a high rate of acute toxicity, including dysphagia and aspiration pneumonia. Aspiration pneumonia often requires...

A Phase 3 Trial to Test Accelerated Versus Standard Fractionation in Combination With Concurrent Cisplatin for Head and Neck Carcinomas (RTOG 0129): Long-term Report of Efficacy and Toxicity

A Phase 3 Trial to Test Accelerated Versus Standard Fractionation in Combination With Concurrent Cisplatin for Head and Neck Carcinomas (RTOG 0129): Long-term Report of Efficacy and Toxicity

Relationship Between Radiation Treatment Time and Overall Survival After Induction Chemotherapy for Locally Advanced Head-and-Neck Carcinoma: A Subset Analysis of TAX 324

To analyze the relationship between overall survival (OS) and radiation treatment time (RTT) and overall treatment time (OTT) in a well-described sequential therapy paradigm for locally advanced head-and-neck carcinoma (LAHNC). TAX 324 is a Phase III study comparing TPF (docetaxel, cisplatin, and fluorouracil) with PF (cisplatin and fluorouracil) induction chemotherapy (IC) in LAHNC patients; both arms were followed by carboplatin-based chemoradiotherapy (CRT). Prospective radiotherapy quality assurance was performed. This analysis includes all patients who received three cycles of IC and a radiation dose of ≥70 Gy. Radiotherapy treatment time was analyzed as binary (≤8 weeks vs. longer) and continuous (number of days beyond 8 weeks) functions. The primary analysis assessed the relationship between RTT, OTT, and OS, and the secondary analysis explored the association between treatment times and locoregional recurrence (LRR). A total of 333 (of 501) TAX 324 patients met the criteria for inclusion in this analysis. There were no significant differences between the treatment arms in baseline or treatment characteristics. On multivariable analysis, PF IC, World Health Organization performance status of 1, non-oropharynx site, T3/4 stage, N3 status, and prolonged RTT (hazard ratio 1.63, p=0.006) were associated with significantly inferior survival. Performance status, T3/4 disease, and prolonged RTT (odds ratio 1.68, p=0.047) were independently and negatively related to LRR on multivariable analysis, whereas PF was not. Overall treatment time was not independently associated with either OS or LRR. In this secondary analysis of the TAX 324 trial, TPF IC remains superior to PF IC after controlling for radiotherapy delivery time. Even with optimal IC and concurrent chemotherapy, a non-prolonged RTT is a crucial determinant of treatment success. Appropriate delivery of radiotherapy after IC remains essential for optimizing OS in LAHNC.

Relationship between Radiation Treatment Parameters and Overall Survival following Induction Chemotherapy in a Sequential Regimen for Locally Advanced Head and Neck Carcinoma (LAHNC): A Subset Analysis of TAX324

Relationship between Radiation Treatment Parameters and Overall Survival following Induction Chemotherapy in a Sequential Regimen for Locally Advanced Head and Neck Carcinoma (LAHNC): A Subset Analysis of TAX324

Induction docetaxel and S-1 followed by concomitant radiotherapy with low-dose daily cisplatin in locally advanced head and neck carcinoma.

e16020 Background: To assess the efficacy and safety of induction chemotherapy with docetaxel (40 mg/m2 d1) and S-1 (40 mg/m2 bid d1-14) (DS), and radiotherapy with concurrent daily cisplatin (6 mg/m2) (PX) in locally advanced head and neck carcinoma (LAHNC). Methods: Twenty-five patients with LAHNC [stage III or IV (M0)] arising from the oral cavity, larynx, oropharynx, or hypopharynx received two cycles of induction chemotherapy with DS, followed by seven cycles of PX. Results: All patients had stage IV. The most common site of the primary tumor was the oropharynx (56%). Twenty- one (84%) of 25 eligible patients completed DS. The most frequent grade 3-4 hematologic toxicity was neutropenia (20%). The median relative dose intensity (RDI) of docetaxel and S-1 was 1.0 (range, 0.94-1.0) and 1.0 (range, 0.34≂f1.0), respectively. Twenty of 21 patients who completed DS started PX, all within 3 to 4 weeks after the start of the second cycle of DS. The most common grade 3 nonhematologic toxicity of PX was mucosi...

Phase I/II trial of induction chemotherapy in locally advanced head and neck carcinoma (LAHNC) and recurrent disease (RD) after surgery/radiotherapy with weekly docetaxel (D), tomudex (T) and cisplatin (P)—DTP

15536 Background: The role of neoadjuvant chemotherapy in LAHNC and treatment for RD have not been established yet. Infusional 5-FU combination with DP is one of the most active regimens for patients (pts) with LAHNC, at the same time is very toxic (hematological, gastrointestinal (GI) and cardiovascular). In order to reduce its toxicity we designed a novel weekly triple-drug scheme trying to reduce toxicity and mantain the high response rate. Methods: LAHNC and RD pts received D 35/mg/m2, T 1 mg/m2 and P 25 mg/m2 on days 1, 8 and 15. with one week rest. Some pts received only days 1 and 8 due to hematological toxicity (grade 2, 3 or 4). Planned treatment included 3 through 6 cycles (50% pts received 3 cycles). After neoadjuvant chemotherapy, pts with LAHNC were sent to their doctors to continue the treatment according to their own preference (surgery, RXT or RXT/QT). Results: Between november 2001 and may 2004, 24 pts (M = 17 F = 7) median age 61 (range 45–72) have been enrolled. 17 was LAHNC and 7 RD; tumor sites were: oral cavity 18 and oropharinx/larinx 6 pts. Response rate (RECIST) and toxicity (NCI) were avaible to all pts. 37.5% pts had grade 3/4 toxicity (hematological or GI) and these pts had a dose reduction. There was one febrile neutropenia and no deaths. The overall rate response was 91.6% (3 CR and 19 PR) in all sites of disease including lymphonodes. Conclusions: This scheme DTP has a high respose rate with low and manageable toxicity. It will be necessary to compare it with concurrent radiotherapy + dose reduction chemotherapy with or without cetuximab. No significant financial relationships to disclose.