Delta-volume radiomics of induction chemotherapy to predict outcome of subsequent chemoradiotherapy for locally advanced hypopharyngeal cancer

2021 ◽  
pp. 030089162110390
Author(s):  
Che-Wei Su ◽  
Jehn-Chuan Lee ◽  
Yi-Fang Chang ◽  
Nai-Wen Su ◽  
Pei-Hsuan Lee ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
Concurrent Chemoradiotherapy ◽  
Locally Advanced ◽  
Area Under The Curve ◽  
Progression Free Survival ◽  
Hypopharyngeal Cancer ◽  
Imaging Biomarker ◽  
Free Survival ◽  
Before And After ◽  
Selection Operator

Introduction: Induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) is recommended for larynx-preserving treatment of locally advanced hypopharyngeal cancer (LAHC). However, the conventional evaluation of response is not robust enough to predict the outcome of subsequent treatments. This study aimed to develop an imaging biomarker using changes in radiomic features in invasive tumor front (ITF) by IC to predict treatment outcome of subsequent CCRT in LAHC. Methods: From 2006 to 2018, 59 computed tomography (CT) scan images before and after IC in patients with LAHC were used to contour the gross tumor volumes (GTVs). A total of 48 delta-volume radiomics features were acquired from the absolute spatial difference of GTVs (delta-GTV) before and after IC, conceptually representing a consistent portion of ITF. Least absolute shrinkage and selection operator regression (LASSO) was used to select features for establishing the model generating radiomic score (R score). Results: A model including 5 radiomic features from delta-GTV to predict better progression-free survival (PFS) of patients receiving subsequent CCRT was established. The R score was validated with all datasets (area under the curve 0.77). Low R score (<–0.16) was associated with improved PFS ( p < 0.05). Conclusions: The established radiomic model for ITF from radiomic features of delta-GTV after IC might be a potential imaging biomarker for predicting clinical outcome of subsequent CCRT in LAHC.

scholarly journals Comparison of Induction Chemotherapy Plus Concurrent Chemoradiotherapy and Concurrent Chemoradiotherapy Alone in Locally Advanced Nasopharyngeal Carcinoma

2021 ◽  
Vol 20 ◽  
pp. 153303382199001
Author(s):  
Guoqiang Xu ◽  
Qiaoli Wang ◽  
Xingrao Wu ◽  
Chunyan Lv ◽  
Guilin Zeng ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Induction Chemotherapy ◽  
Locoregional Recurrence ◽  
Concurrent Chemoradiotherapy ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Survival Outcomes ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Weekly Cisplatin

Purpose: Induction chemotherapy plus concurrent chemoradiotherapy and concurrent chemoradiotherapy alone are both standard treatment regimens for managing locally advanced nasopharyngeal carcinoma. However, the results of comparisons between them in clinical trials vary. Therefore, we designed this meta-analysis to illustrate their advantages and disadvantages in patients with locally advanced nasopharyngeal carcinoma. Methods: We thoroughly searched the PubMed, EMBASE, and Cochrane Library databases and then merged the effect indicators of hazard ratios and risk ratios using RevMan 5.1. Results: Seven randomized controlled trials totaling 2,319 patients were included in our research. The synthesized results showed that induction chemotherapy plus concurrent chemoradiotherapy improved overall survival (HR = 0.75, 95% CI: 0.63-0.89, P = 0.001), progression-free survival (HR = 0.69, 95% CI: 0.60-0.80, P < 0.001), distant metastasis-free survival (HR = 0.65, 95% CI: 0.53-0.80, P < 0.001) and locoregional recurrence-free survival (HR = 0.68 95%, CI: 0.54-0.86, P = 0.001) versus concurrent chemoradiotherapy alone. It also increased the risk of anemia, thrombocytopenia, and neutropenia during concurrent chemoradiotherapy. However, the incidence of leukopenia and mucositis was similar in induction chemotherapy and induction chemotherapy plus concurrent chemoradiotherapy. Furthermore, the subgroup analysis showed better survival outcomes with induction chemotherapy plus concurrent chemoradiotherapy than with concurrent chemoradiotherapy alone in the triweekly cisplatin subgroup (all P < 0.01), whereas induction chemotherapy plus concurrent chemoradiotherapy could only improve progression-free survival and locoregional recurrence-free survival in the weekly cisplatin subgroup (HR = 0.78, P = 0.02; and HR = 0.66, P = 0.03, respectively). Conclusions: Induction chemotherapy plus concurrent chemoradiotherapy improved survival outcomes in patients with locally advanced nasopharyngeal carcinoma versus concurrent chemoradiotherapy. For the weekly cisplatin regimen subgroup, it did not improve remote control or overall survival versus concurrent chemoradiotherapy alone, warranting further clarification.

scholarly journals Induction Chemotherapy Followed by Cetuximab Radiotherapy Is Not Superior to Concurrent Chemoradiotherapy for Head and Neck Carcinomas: Results of the GORTEC 2007-02 Phase III Randomized Trial

2018 ◽  
Vol 36 (31) ◽  
pp. 3077-3083 ◽  
Author(s):  
Lionnel Geoffrois ◽  
Laurent Martin ◽  
Dominique De Raucourt ◽  
Xu Shan Sun ◽  
Yungan Tao ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Induction Chemotherapy ◽  
Squamous Cell ◽  
Concurrent Chemoradiotherapy ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Phase Iii ◽  
Free Survival

Purpose Both concurrent chemoradiotherapy (CT-RT) and cetuximab radiotherapy (cetux-RT) have been established as the standard of care for the treatment of locally advanced squamous cell carcinoma of the head and neck. It was not known whether the addition of induction chemotherapy before cetux-RT could improve outcomes compared with standard of care CT-RT. Patients and Methods The current trial was restricted to patients with nonmetastatic N2b, N2c, or N3 squamous cell carcinoma of the head and neck and fit for taxotere, cisplatin, fluorouracil (TPF). Patients were randomly assigned to receive three cycles of TPF followed by cetux-RT versus concurrent carboplatin fluorouracil and RT as recommended in National Comprehensive Cancer Network guidelines. The trial was powered to detect a hazard ratio (HR) of 0.66 in favor of TPF plus cetux-RT for progression-free survival at 2 years. The inclusion of 180 patients per arm was needed to achieve 80% power at a two-sided significance level of .05. Results Between 2009 and 2013, 370 patients were included. All patients and tumors characteristics were well balanced between arms. There were more cases of grade 3 and 4 neutropenia in the induction arm, and the induction TPF was associated with 6.6% treatment-related deaths. With a median follow-up of 2.8 years, 2-year progression-free survival was not different between both arms (CT-RT, 0.38 v TPF + cetux-RT, 0.36; HR, 0.93 [95% CI, 0.73 to 1.20]; P = .58). HR was 0.98 (95% CI, 0.74 to 1.3; P = .90) for locoregional control and 1.12 (95% CI, 0.86 to 1.46; P = .39) for overall survival. These effects were observed regardless of p16 status. The rate of distant metastases was lower in the TPF arm (HR, 0.54 [95% CI, 0.30 to 0.99]; P = .05). Conclusion Induction TPF followed by cetux-RT did not improve outcomes compared with CT-RT in a population of patients with advanced cervical lymphadenopathy.

scholarly journals RACE-trial: neoadjuvant radiochemotherapy versus chemotherapy for patients with locally advanced, potentially resectable adenocarcinoma of the gastroesophageal junction - a randomized phase III joint study of the AIO, ARO and DGAV

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Sylvie Lorenzen ◽  
Alexander Biederstädt ◽  
Ulrich Ronellenfitsch ◽  
Christoph Reißfelder ◽  
Stefan Mönig ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
Preoperative Chemotherapy ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Neoadjuvant Radiochemotherapy ◽  
Perioperative Chemotherapy ◽  
Free Survival ◽  
Link Type

Abstract Background Despite obvious advances over the last decades, locally advanced adenocarcinomas of the gastroesophageal junction (GEJ) still carry a dismal prognosis with overall 5-year survival rates of less than 50% even when using modern optimized treatment protocols such as perioperative chemotherapy based on the FLOT regimen or radiochemotherapy. Therefore the question remains whether neoadjuvant chemotherapy or neoadjuvant radiochemotherapy is eliciting the best results in patients with GEJ cancer. Hence, an adequately powered multicentre trial comparing both therapeutic strategies is clearly warranted. Methods The RACE trial is a an investigator initiated multicenter, prospective, randomized, stratified phase III clinical trial and seeks to investigate the role of preoperative induction chemotherapy (2 cycles of FLOT: 5-FU, leucovorin, oxaliplatin, docetaxel) with subsequent preoperative radiochemotherapy (oxaliplatin weekly, 5-FU plus concurrent fractioned radiotherapy to a dose of 45 Gy) compared to preoperative chemotherapy alone (4 cycles of FLOT), both followed by resection and postoperative completion of chemotherapy (4 cycles of FLOT), in the treatment of locally advanced, potentially resectable adenocarcinoma of the gastroesophageal junction. Patients with cT3–4, any N, M0 or cT2 N+, M0 adenocarcinoma of the GEJ are eligible for inclusion. The RACE trial aims to enrol 340 patients to be allocated to both treatment arms in a 1:1 ratio stratified by tumour site. The primary endpoint of the trial is progression-free survival assessed with follow-up of maximum 60 months. Secondary endpoints include overall survival, R0 resection rate, number of harvested lymph nodes, site of tumour relapse, perioperative morbidity and mortality, safety and toxicity and quality of life. Discussion The RACE trial compares induction chemotherapy with FLOT followed by preoperative oxaliplatin and 5-Fluorouracil-based chemoradiation versus preoperative chemotherapy with FLOT alone, both followed by surgery and postoperative completion of FLOT chemotherapy in the treatment of locally advanced, non-metastatic adenocarcinoma of the GEJ. The trial aims to show superiority of the combined chemotherapy/radiochemotherapy treatment, assessed by progression-free survival, over perioperative chemotherapy alone. Trial registration ClinicalTrials.gov; NCT04375605; Registered 4th May 2020;

Safety and efficacy of docetaxel combined with cisplatin as induction chemotherapy followed by cisplatin concurrent chemoradiotherapy plus gemcitabine as adjuvant chemotherapy in locally advanced nasopharyngeal carcinoma: A prospective and multicenter phase II trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6064-6064
Author(s):  
Zhi Hui Wang ◽  
Peijian Peng ◽  
Siyang Wang ◽  
Yumeng Liu ◽  
Zhong Lin
Keyword(s):  
Radiation Therapy ◽  
Adjuvant Chemotherapy ◽  
Induction Chemotherapy ◽  
Treatment Strategy ◽  
Objective Response ◽  
Locally Advanced ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Free Survival ◽  
Safety And Efficacy

6064 Background: Radiation therapy is the only curative treatment modality for nonmetastatic nasopharyngeal cancer (NPC). Concurrent chemoradiation (CCRT) is the standard treatment strategy for NPC in locally advanced stages. However, the results after such treatment are suboptimal. Clearly, novel treatment strategies are needed to further improve patients’ survival rates. This trial aimed to determine the safety and efficacy of a new treatment strategy. Methods: Patients with stage III – IVa-b NPC received TP (docetaxel 75 mg/m2, cisplatin 75 mg/m2 every 3 weeks for 2-3 cycles) followed by cisplatin chemotherapy concurrently with either 3-dimentional conformal radiation therapy or intensity-modulated radiation therapy plus gemcitabine (1000mg/m2 every 2 weeks for 2 cycles) as adjuvant chemotherapy. Objective response rates and acute toxicity were assessed based on RECIST (1.1) and CTCAE v.4.0, respectively. Kaplan-Meier analysis was used to calculate survival rates. This trial is registered with the Chinese Clinical Trials Registry, number ChiCTR-OIC-17011464. Results: From July 2010 to July 2017, 20 eligible patients with nonmetastatic stage III-IVb NPC were enrolled. The objective response rates were 90% (3 complete responses [CRs] and 15 partial responses [PRs]) after two or three cycles of induction chemotherapy (ICT) and 100% (17 CRs and three PRs) after CCRT plus gemcitabine adjuvant chemotherapy, respectively. With a median follow-up time of 41 months, the 3-year overall survival rates were 90% (18/20,95% confidence interval [CI], 76.9%-100%).The 3-year progression-free survival, distant metastasis-free survival, and local progression-free survival rates were 80% (16/20,95% CI, 62.5%-97.5%), 85% (17/20,95% CI, 69.4%-100%),95% (19/20,95% CI, 85,4%-100%), respectively. The most frequent grade 3–4 toxicities were neutropenia (3/20,15%) and nausea (2/20,10%) after ICT and thrombocytopenia (6/20,30%) and leukopenia (6/20,30%) after CCRT plus gemcitabine adjuvant chemotherapy. Conclusions: Neoadjuvant TP followed by concurrent chemoradiation plus gemcitabine as adjuvant chemotherapy was well tolerated and produced promising outcomes in patients with LA-NPC in this hypothesis-generating study. The authors concluded that randomized controlled trials are warranted to definitively confirm this aggressive and potentially efficacious strategy. Clinical trial information: ChiCTR-OIC-17011464.

A multicenter randomized phase II study of full-dose gemcitabine and concurrent radiotherapy comparing gemcitabine alone for the unresectable locally advanced pancreatic adenocarcinoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15512-e15512
Author(s):  
T. Ioka ◽  
R. Takakura ◽  
A. Nakaizumi ◽  
S. Tanaka ◽  
H. Iishi ◽  
...  
Keyword(s):  
Pancreatic Adenocarcinoma ◽  
Concurrent Chemoradiotherapy ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Free Survival ◽  
Full Dose ◽  
Concurrent Radiotherapy ◽  
Pancreatic Cancers ◽  
Randomized Phase Ii ◽  
Locally Advanced Pancreatic Adenocarcinoma

e15512 Background: Some of locally advanced pancreatic cancers (LAPC) are considered to include a potential micro metastasis. We think that full-dose of gemcitabine (GEM) improve the outcome of LAPC. We report the efficacy of full-dose GEM and concurrent radiotherapy, comparing GEM alone for unresectable LAPC. Methods: Patients with histologically or cytologically proven pancreatic adenocarcinoma were eligible for this study. We decide that LAPA which involved a major artery with CT imaging was unresectable. Patients were randomized into a concurrent chemoradiotherapy (CRT) group and a chemotherapy alone (CTX) group. GEM was given intravenously at a dose of 1,000 mg/msq over 30 min on days 1, 8 and 15 of each 28-day cycle and repeated until disease progression in both groups. Patients randomized into CRT group received a limited field irradiation with a total dose of 50 Gy in 25 sessions during first two cycles. The two groups were compared for mean survival, progression free survival and safety. Results: From September 2002 to April 2005, 80 patients were randomized at two institutions into the two arms of the trial (40 patients to CRT group and 40 patients to CTX group). The CRT group had better results than the CTX group as measured by mean survival time (391 vs 372 days, P< 0.02) and progression free survival (237 vs 128 days, P< 0.01). There were no differences in the safety between both groups. Conclusions: The concurrent chemoradiotherapy with full-dose GEM is effective and feasible in patients of LAPC compared with full-dose GEM alone. No significant financial relationships to disclose.

Phase II Study of Induction Chemotherapy with Gemcitabine plus 5-Fluorouracil Followed by Gemcitabine-Based Concurrent Chemoradiotherapy for Unresectable Locally Advanced Pancreatic Cancer

2006 ◽  
Vol 92 (6) ◽  
pp. 481-486 ◽  
Author(s):  
Ender Kurt ◽  
Meral Kurt ◽  
Ozkan Kanat ◽  
Sibel Kahraman Cetintas ◽  
Sevilcan Aygun ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Induction Chemotherapy ◽  
Concurrent Chemoradiotherapy ◽  
External Beam Radiotherapy ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Locally Advanced Pancreatic Cancer ◽  
Disease Stabilization ◽  
Grade 3

Aims and background To evaluate the efficacy and tolerability of a new treatment approach including induction chemotherapy (CT) and concurrent chemoradiotherapy (CRT) in unresectable, locally advanced pancreatic cancer (LAPC). Patients and methods Twenty-four patients with LAPC were enrolled in the study. They first received induction CT consisting of 5-fluorouracil (5FU) (500 mg/m2) and gemcitabine (1000 mg/m2), which were given weekly for 3 weeks of every 4. Patients showing a response or disease stabilization after 2 cycles of induction CT received CRT consisting of external beam radiotherapy (50.4-54 Gy in fractions of 1.8 Gy/day) and gemcitabine (350 mg/m2, weekly for 6 weeks). Patients without disease progression received 2 additional cycles of CT consisting of 5FU plus gemcitabine with the same doses and schedule as given in the induction CT. Results After the end of the study, 2 (8%) and 5 (21%) patients showed complete and partial responses, respectively. Five patients (21%) had disease stabilization. The grade 3 and 4 toxicities associated with CT were neutropenia (21%) and thrombocytopenia (4%). The grade 3 and 4 toxicities occurring in patients who received CRT were neutropenia (24%), thrombocytopenia (24%), diarrhea (18%), and nausea (12%). The median progression-free survival for all patients was 6 months (95% CI, 3.6-8.4), and the median overall survival was 11 months (95% CI, 8.16-13.84). Conclusions The CRT approach of this study is moderately active and has an acceptable toxicity profile. However, the incor-poration of combination CT into CRT at the present schedule could not produce any additional benefit over CRT alone. Newer agents with more systemic activity are clearly warranted.

scholarly journals The Most Efficacious Induction Chemotherapy Regimen for Locoregionally Advanced Nasopharyngeal Carcinoma: A Network Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Horace Cheuk-Wai Choi ◽  
Sik-Kwan Chan ◽  
Ka-On Lam ◽  
Sum-Yin Chan ◽  
Sze-Chun Chau ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Induction Chemotherapy ◽  
Fixed Effects ◽  
Concurrent Chemoradiotherapy ◽  
Meta Analysis ◽  
Intensity Modulated Radiation Therapy ◽  
Progression Free Survival ◽  
Free Survival ◽  
Hazard Ratios ◽  
Analysis Models

BackgroundInduction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) for non-metastatic locoregionally advanced nasopharyngeal carcinoma (NPC) has gained considerable attention. However, the most efficacious IC regimens remain investigational. We aimed to compare the survival benefits of all available IC regimens followed by CCRT in this network meta-analysis.MethodsAll randomized-controlled trials of CCRT with or without IC in non-metastatic locoregionally advanced NPC were included, with an overall nine trials of 2,705 patients counted in the analysis. CCRT alone was the reference category. Eight IC regimens followed by CCRT were analyzed: docetaxel + cisplatin (DC), gemcitabine + carboplatin + paclitaxel (GCP), gemcitabine + cisplatin (GP), mitomycin + epirubicin + cisplatin + fluorouracil + leucovorin (MEPFL), cisplatin + epirubicin + paclitaxel (PET), cisplatin + fluorouracil (PF), cisplatin + capecitabine (PX) and cisplatin + fluorouracil (PF), cisplatin + capecitabine (PX). Fixed-effects frequentist network meta-analysis models was applied and P-score was used to rank the treatments.ResultsDC, GP, and PX were the top three IC regimens with the highest probability of benefit on overall survival (OS). Their corresponding hazard ratios (HRs) (95% CIs) compared with CCRT alone were of 0.24 (0.08–0.73), 0.43 (0.24–0.77), and 0.54 (0.27–1.09) and the respective P-scores were 94%, 82%, and 68%. The first three IC regimens showing significantly improved progression-free survival (PFS) were PX, followed by GP and DC with respective HRs of 0.46 (0.24–0.88), 0.51 (0.34–0.77), and 0.49 (0.20–1.20), and P-scores of 82%, 78%, and 74%. Among the studies in the intensity-modulated radiation therapy (IMRT) era, GP and PX were the best performed IC regimens, whilst DC performed the best among non-IMRT studies. Doublet and gemcitabine-based IC regimens had better survival benefits compared to triplet and taxane-based IC regimens, respectively.ConclusionsGiven its consistent superiority in both OS and PFS, DC, GP, and PX ranked among the three most efficacious IC regimens in both the overall and subgroup analysis of IMRT or non-IMRT studies. Exploratory analyses suggested that doublet and gemcitabine-based IC regimens showed better survival performance.

Comparison of Nedaplatin- and Cisplatin-Based Concurrent Chemoradiotherapy in Locally Advanced Cervical Cancer Patients: A Propensity Score Analysis

2018 ◽  
Vol 28 (5) ◽  
pp. 1029-1037
Author(s):  
Ping Li ◽  
Rui Zhang ◽  
Zhihua Nie ◽  
Mengjuan Long ◽  
Gong Zhang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Propensity Score ◽  
Concurrent Chemoradiotherapy ◽  
Propensity Score Analysis ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Advanced Cervical Cancer ◽  
Free Survival ◽  
Locally Advanced Cervical Cancer ◽  
Score Analysis

PurposeThe aim of this study was to evaluate the efficacy of using nedaplatin to replace cisplatin for concurrent chemoradiotherapy (CCRT) in patients with newly diagnosed locally advanced cervical cancer.MethodsThe medical records of 155 patients with cervical cancer who had undergone CCRT with cisplatin (n = 85) or nedaplatin (n = 70) between January 2012 and January 2017 were retrospectively reviewed. Propensity score analysis with 1:1 matching with the nearest neighbor matching method was performed to assess response rates, progression-free survival, overall survival, and toxicity between 2 groups.ResultsPropensity score matching identified 63 patients in each group. After matching, compared with patients treated with cisplatin-based concurrent chemoradiotherapy (CisRT), we found that patients treated with nedaplatin-based concurrent chemoradiotherapy (NedaRT) had a significant higher recurrence rate (25.4% vs 42.9%; P = 0.04). In addition, the 3-year progression-free survival rate for NedaRT group was also worse than that for the CisRT group (52.2% vs 63.4%, P = 0.03). There was no difference in the overall response rates between the CisRT and NedaRT groups (87.3% and 90.5%, respectively; P = 0.57). The rates of 3-year overall survival and grades 3 to 4 toxicities were similar between the 2 groups.ConclusionsThe clinical outcome of this cohort of patients with locally advanced cervical cancer treated with CCRT did in no way provide support for the use of nedaplatin in place of cisplatin in chemoradiation and demonstrated no equivalence of the 2 drugs. Cautions should be taken for the replacement among platinum complexes in cancer treatment.

scholarly journals Induction Chemotherapy with Docetaxel, Cisplatin and 5-Fluorouracil (TPF) Followed by Chemoradiotherapy for Locally Advanced Head and Neck Cancer: Can It Achieve Its Potential?

2020 ◽  
pp. 1-10
Author(s):  
Nicholas P Rowell ◽  
Nicholas P Rowell
Keyword(s):  
Overall Survival ◽  
Induction Chemotherapy ◽  
Treatment Time ◽  
Locally Advanced ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Advanced Head ◽  
Free Survival ◽  
The Mean ◽  
Delivered Dose

Objective: In view of concerns about toxicity and deliverability of induction chemotherapy and its impact on subsequent chemoradiotherapy, a retrospective review was carried out with patients treated for locally advanced head and neck cancer (LAHNC) in a single centre between 2007-2017. Patients and Interventions: Patients with LAHNC and good performance status receiving induction chemotherapy with docetaxel, cisplatin and 5-fluorouracil (TPF) followed by chemoradiotherapy to 70Gy in 35 daily fractions with platinum-based chemotherapy. Main Outcome Measures: Overall and cause-specific survival, rates of locoregional recurrence or distant metastasis, treatment-related toxicity. Results: One hundred and eight patients with LAHNC were treated with 1-4 cycles of TPF (95 receiving two cycles) followed by chemoradiotherapy. The mean delivered dose intensity was 97.6% for all TPF cycles. Median interval from the start of the final cycle of TPF to the start of radiotherapy was 24 days, with 92/103 (89%) starting radiotherapy within 28 days. Median radiation treatment time was 47 days. The mean delivered dose intensity for chemotherapy delivered concurrently with radiotherapy was 97%. There were significantly fewer dose reductions in those receiving platinum/5FU combinations than platinum only regimes (P < 0.0001). For those receiving two cycles of TPF, 90% of patients completed the whole course of treatment within 14 weeks (median overall treatment time 13.1 weeks). There were four treatment-related deaths during induction chemotherapy and none during radiotherapy. Twenty-five developed locoregional failure and 13 distant metastases (both in eight). Actuarial overall survival was 60.7% at five years, with progression-free survival of 77.9% at two years and 74.1% at five years. For oropharynx cancers, overall survival was 70.4% and progression-free survival 80.8% at five years. Conclusion: Although significant toxicity from TPF was observed, with appropriate support, it is possible to complete treatment without undue compromise of subsequent treatment.

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