Altered Fractionation Radiotherapy Research Articles

Carcinoma buccal mucosa treated with definitive hypofractionated accelerated radiotherapy: a retrospective analysis of treatment outcomes.

Oral cancer is a major public health concern in India. Both conventional and altered fractionation radiotherapy schedules have been used in curative treatment of oral cancer. This study aimed to retrospectively evaluate the clinical profile and treatment outcomes of patients with carcinoma buccal mucosa who underwent treatment with definitive hypofractionated accelerated radiotherapy. A total of 517 patients treated from January 2011 to December 2016 were eligible for the analysis. All patients were treated with definitive hypofractionated accelerated radiotherapy schedule of 5,250 cGy in 15 fractions over 3 weeks. Survival estimates were generated using the Kaplan-Meier method. At a median follow-up of 77.4 months, 473 (91.5%) patients attained complete remission with radiation therapy. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 69% and 80.5%, respectively. The 5-year OS for stage I, II, III and IVa tumours was 80.3%, 84.4%, 81.4% and 73.7%, respectively, and the DFS was 75.7%, 73.2%, 69.6% and 60.2%, respectively. Age >50 years was found to be a significant factor affecting DFS (P = 0.026) and OS (P = 0.048) in multivariate analysis. Fifty-three (10.3%) patients developed osteoradionecrosis of the mandible. Excellent outcome could be achieved in less-aggressive, low-volume carcinoma of the buccal mucosa with radical accelerated hypofractionated radiotherapy. A radiotherapy schedule over a 3-week period is useful in high-volume centres.

A COMPARATIVE PROSPECTIVE STUDY BETWEEN STANDARD AND ALTEREDFRACTIONATED RADIOTHERAPY FOR LOCALLY ADVANCED HEAD AND NECKSQUAMOUS CELL CARCINOMA

Background and Purpose: To compare conventionally fractionated chemoradiotherapy (CF-CRT) with two variants of altered fractionated radiotherapy (AFRT) in patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC). 64 patients diagnosed with LAHNSCC were randomized Material and Methods: either to receive CF-CRT (70 Gy/35 fractions) in Arm-I or hyper-fractionation radiotherapy (HFRT 81.6 Gy/68 fractions 1.2 Gy BID) in Arm-II or concomitant boost radiotherapy (CBT 71.6 Gy/28 fractions with last 16 fractions BID as concomitant boost) in Arm-III. 35mg/m2 cisplatin weekly was given as concurrent chemotherapy regimen in Arm-I. The primary objective was to assess acute toxicity, and the secondary endpoint was the radiotherapeutic response between CF-CRT and AFRT. Radiation Therapy Oncology Group (RTOG) criteria were used for evaluating acute toxicity. Response Evaluation Criteria In Solid Tumor 1.1 (RECIST 1.1) was used to assess response. Twenty-two, 21, and 21 Results: patients were randomly assigned to Arm-I, II, and III. The treatment was completed by 22, 17, and 18 patients in Arm-I, II, and III. The acute Grade-II skin toxicity was higher in Arm-II (58.8%) and III (50.0%) compared to Arm-I (36.3 %), but the correlation was insignicant (p- .17). Acute Grade-III mucosal toxicity was higher in Arm-II (35.2%) and III (38.8%), and it shows a trend towards signicance (p- .059). Arm-II had higher complete responder (52.9%) compared to Arm-I (27.2%), and the correlation was insignicant (p- .23). The AFRT Conclusion: arms II and III showed similar radiotherapeutic response as CF-CRT arm. Comparable acute toxicities were seen in all arms except for the mucosal toxicity, which was higher in Arm-II and III

Ensuring Superior Reporting of Non-Inferiority Radiotherapy Clinical Trials: A Systematic Review

<h3>Purpose/Objective(s)</h3> Non-inferiority clinical trials are used to investigate whether a new treatment is not worse than a control by an acceptable amount. These new treatments can be more convenient, cost-effective, or tolerable than the standard of care. Although the frequency of this trial design is increasing, the consistency of reporting and interpretation of these trials can vary. The aim of this systematic review was to assess the methodologic quality of non-inferiority radiotherapy clinical trials. <h3>Materials/Methods</h3> A literature search of PubMed, EMBASE and Cochrane databases of randomized controlled radiotherapy trials with non-inferiority hypotheses published in English between January 2000 and July 2021 was performed by an information scientist. Exclusion criteria included study protocols, and follow-up or interim analyses. Records were screened and full texts were reviewed by two authors with discrepancies settled by a third reviewer or by consensus. Descriptive statistics pertaining to study size, primary cancer type, type of comparison, endpoint, and statistical measures were performed. This review was prospectively registered on PROSPERO: CRD42021270644. <h3>Results</h3> Of 260 records identified on initial search, 44 (17%) trials were included after full-text review. The mean number of participants was 876 (IQR: 216.25–912.5). All were published after 2004, and open label. Four (9%) trials were funded by industry. The most common primary cancer type was breast (n=10, 23%). Most studies (n=37, 84%) had 2 treatment arms. The most common types of interventions included altered radiation fractionation (n=13, 30%) and changes to systemic therapy agents (n=10, 23%). Six (14%) studies compared radiation to another treatment modality (e.g., surgery, radiofrequency ablation), and 3 (7%) studies examined the omission of radiation. The most common primary endpoints were progression-free survival (n=12, 27%) and local/regional control (n=12, 27%). Forty (91%) studies reported the non-inferiority margin, and only 5 (11%) studies provided a statistical rationale for the margin. The median non-inferiority margin was 10% (IQR: 5–10%). Sample size calculation was reported in 42 (95%) studies, and 42 (95%) studies reported confidence intervals of the primary endpoint. Both intention-to-treat and per protocol analyses were reported in the majority (52%) of studies. In 23 (52%) trials, a non-inferiority claim of the primary endpoint was reached. <h3>Conclusion</h3> Clinical trials with a non-inferiority design are relatively uncommon in radiation oncology, and have been used for variable types of comparisons and primary endpoints. Standardization of required data to report and statistical methodology would be helpful to ensure proper interpretation of trial results.

Comparison of different treatments for HPV+ oropharyngeal carcinoma: a network meta-analysis.

Treatment of human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) is rapidly evolving. Despite either surgery or radiotherapy (RT), with or without chemotherapy (CT), being acceptable in intermediate and locally advanced diseases, there is uncertainty regarding the best treatment option for these patients. Therefore, we performed a network meta-analysis (NMA) to compare the relative efficacy of different treatments for HPV+ oropharyngeal carcinoma. Randomized clinical trials that enrolled adults with non-metastatic HPV+ oropharynx cancer and provided data about overall survival (OS) and/or progression-free survival (PFS) and/or locoregional control and distant metastases (LRC and DM) were included. Fixed- or random-effects models were fit using a Bayesian approach to NMA. Between-group comparisons were estimated using hazard ratios (HRs) with 95% credible intervals (CrIs). The primary outcome was OS. A total of 844 citations were screened; 11 randomized clinical trials were included (HPV+ stage III-IV cancer, mainly oropharynx carcinomas). Nine treatment arms were compared. Radiotherapy (altered or standard fractionation) + triweekly cisplatin (HR 3.8; 95% CrIs 0.29-65 and 0.3; 95% CrIs 0.03-2.51) was superior to RT in term of OS (P score = 0.42 and 0.16). Radiotherapy with low and high cisplatin doses appeared similar (HR 1.57; 95% CrIs 0.19-12.72). Altered fractionation or standard RT + 3-weekly cisplatin are the 2 highest-ranked options in terms of PFS (P score = 0.35 and 0.34). This meta-analysis confirms the role of cisplatin added to RT as the best option for HPV+ oropharyngeal carcinoma. RT+ 3-weekly cisplatin is likely to be the best radical treatment in terms of OS and PFS.

Altered-Fractionation Radiotherapy Improves Local Control in T1 but Not T2 Early-Stage Glottic Carcinoma: A Systematic Review and Meta-Analysis of 1816 Patients

Altered-Fractionation Radiotherapy Improves Local Control in T1 but Not T2 Early-Stage Glottic Carcinoma: A Systematic Review and Meta-Analysis of 1816 Patients

Altered-fractionation radiotherapy improves local control in early-stage glottic carcinoma: A systematic review and meta-analysis of 1762 patients

ObjectivesTo perform a systematic review of 1762 patients to comprehensively assess the benefit of altered-fractionation radiotherapy (ART) in early stage glottic carcinoma (ESGC). Materials and methodsStudies were identified in PubMed and EMBASE. Inclusion criteria were: (1) diagnosis of squamous cell ESGC (Tis, T1, T2); (2) ART versus conventionally-fractionationated radiotherapy (CRT); and (3) provision of number of local recurrence events and total numbers per fractionation arm. The random-effects model was fitted to estimate the pooled hazard ratio (HR). Subgroup sensitivity analyses were performed based on ART strategy (hypo- versus hyperfractionation), treatment-day reductions, machine type, tumor stage, and anterior commissure involvement. ResultsEleven studies met inclusion criteria: 4 randomized controlled trials (RCTs) and 7 two-arm retrospective studies. ART was associated with 38% fewer (HR 0.62; 95% CI: 0.46–0.82, p = 0.0009) and 60% fewer (HR 0.40; 95% CI: 0.24–0.66, p = 0.0003) local failure events in pooled analyses of the RCTs and retrospective studies, respectively. Both hyperfractionation (HR 0.65; 95% CI: 0.43–0.97, p = 0.03) and hypofractionation (HR 0.55; 95% CI: 0.33–0.91, p = 0.02) strategies were superior to CRT. The benefit persisted for all treatment- and tumor-related parameters, including anterior commissure involvement, with the exception of a pooled analysis of studies with predominantly T2 (<50% T1) cases (HR 0.60, 95% CI: 0.30–1.20, p = 0.15). ConclusionBoth hypofractionation and hyperfractionation improve local control in ESGC, including T1 tumors and for anterior commissure involvement. However, this benefit may not persist for T2 tumors, for which alternative strategies should be considered.

Low-Dose vs. High-Dose Cisplatin: Lessons Learned From 59 Chemoradiotherapy Trials in Head and Neck Cancer.

In locally advanced squamous cell carcinomas of the head and neck (LA-SCCHN), concurrent chemoradiotherapy is an integral part of multimodality management both in the adjuvant and in the definitive settings. Although de-intensification strategies have been propelled to the forefront of clinical research in human papillomavirus (HPV) positive oropharyngeal cancer, three cycles of 100 mg/m2 cisplatin given every 3 weeks concurrently with conventionally fractionated external beam radiotherapy represent a cost-effective and globally accessible treatment option for the majority of LA-SCCHN cases. Based on four large randomized trials, this regimen has become the non-surgical standard of care for cisplatin-eligible patients. Nevertheless, the outcomes in terms of efficacy, toxicity, and compliance have been rather disappointing. Therefore, there is an unmet need to find a better alternative. With limited support from randomized trials, weekly low-dose cisplatin regimens have replaced the standard high-dose schedule at some institutions. Four prospective trials exploring radiotherapy with and without weekly low-dose cisplatin have been published. Two of them were conducted in the 1980s, one of which had a negative outcome, the third study provided insufficient information on toxicity, and the fourth trial had to be prematurely terminated due to poor accrual. Moreover, the findings of two phase III trials comparing the two concurrent cisplatin regimens favored the high-dose protocol. We performed a composite meta-analysis of 59 prospective trials enrolling a total of 5,582 patients. The primary endpoint was overall survival. Reflecting different radiotherapy fractionation schemes and treatment intents, three meta-analyses were carried out, one for postoperative conventional chemoradiotherapy, one for definitive conventional chemoradiotherapy, and one for definitive altered fractionation chemoradiotherapy. In the former two settings, both high- and low-dose regimens yielded similar survival outcomes, thus, the primary objective was not met. When given concurrently with altered fractionation radiotherapy, patients treated with high-dose cisplatin had significantly longer overall survival than those who received low-dose cisplatin. In this article we provide a synthetic view of the results, discuss the issue of cumulative dose, compare two vs. three cycles of high-dose cisplatin, and present our three-step recommendations for use of the current standard of care, high-dose cisplatin, in clinical practice.

РЕЖИМЫ НЕТРАДИЦИОННОГО ФРАКЦИОНИРОВАНИЯ В ЛУЧЕВОЙ ТЕРАПИИ РАКА ГОЛОВЫ И ШЕИ

The purpose of the review is to analyze and summarize literature data about the role of altered fractionation radiotherapy for head and neck cancer. A total of 46 English-language literature sources were analyzed. They provide a radiobiological rationale for altered fractionation, whose efficacy as compared with conventional radiation therapy, has been confirmed in clinical studies. The results of these studies indicate the greatest benefit with the application of hyperfractionation and moderately accelerated fractionation in patients with squamous cell carcinoma of the head and neck.

Genetics and management of locally advanced carcinomas of the head and neck: role of altered fractionation radiotherapy.

Squamous cell carcinoma of the head and neck (SCCHN) accounts for 5–7% of all malignancies. About 60% of newly diagnosed SCCHN are detected as locally advanced disease. Chemoradiation is a standard option and response rate to it is variable. Recently, a genetic classification of SCCHN has been proposed by Chung et al., who categorized all SCCHN into four subtypes. The basal-like variant is characterized by high expression of EGFR. Literature data suggest higher efficacy of accelerated and/or hyperfractionated radiotherapy, if compared with conventional radiotherapy in the subgroup of patients with high EGFR expression. In this review, we will describe the genetic factors able to guide treatment choice, with a focus on EGFR expression.

Altered fractionation radiotherapy with or without chemotherapy in the treatment of head and neck cancer: a network meta-analysis.

ObjectivesA Bayesian network meta-analysis (NMA) was conducted in patients with head and neck cancers (HNCs) to estimate the efficacy and safety of treatment with conventional fractionation radiotherapy (CF), conventional fractionation chemoradiotherapy (CF_CRT), hyperfractionated radiotherapy (HF), hyperfractionated chemoradiotherapy (HF_CRT), accelerated fractionation radiotherapy, accelerated fractionation chemoradiotherapy, accelerated hyperfractionated radiotherapy (HART) or accelerated hyperfractionated chemoradiotherapy (HACRT) to identify superior treatments to aid in clinical decisions.MethodsPubMed, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched for potentially eligible randomized controlled trials up to December 2016. Overall survival (OS), disease-free survival (DFS) and locoregional control (LRC) were considered efficacy outcomes, whereas acute toxicity and late toxicity on skin and mucosa were considered safety outcomes. The surface under the cumulative ranking curve (SUCRA) was calculated to rank each treatment in each index.ResultsData from 72 trials with 21,868 participants were included in the analysis. Concerning OS, all treatments were associated with a significant advantage compared to CF alone, with HR effect sizes ranging from 0.64 to 0.83, and HACRT was significantly more effective than all the other treatments. The network comparisons of both HACRT vs HART and HF_CRT vs HF demonstrated a higher OS benefit, with an HR of 0.78 (95% credible interval [CrI]: 0.64–0.95) and 0.78 (95% CrI: 0.61–0.99), respectively. The results of SUCRA indicated that HACRT had the best ranking for OS and LRC, HF_CRT for DFS, HART for acute and late skin toxicity, CF_CRT for acute mucosal toxicity and HF_CRT for late mucosal toxicity.ConclusionThe NMA results support the notion that HACRT is the preferable treatment modality for HNCs because it has better rankings in all three efficacy indexes, although it does present a high risk of acute mucosal toxicity.

Locally advanced squamous cell carcinoma of the head and neck: A systematic review and Bayesian network meta-analysis of the currently available treatment options

BackgroundThere are still many unresolved questions in the management of locally advanced Head and Neck Cancer (HNC). Many chemotherapeutic drugs and radiotherapy fractionation schemes are available and not all have been evaluated in head-to-head clinical trials. This systematic review and Bayesian network meta-analysis aims to compare the available treatment strategies and chemotherapeutic options for locally advanced HNC. MethodsWe performed a search on bibliography databases, trials registries and meetings proceedings for published and unpublished randomized trials from January 1st 2000 to December 1st 2017. Trials had to compare systemic interventions and radiotherapy (RT) approaches for locally advanced, non-metastatic HNC. Trials recruiting patients whose surgery was the first treatment option, sample size less than 20 per arm or that did not use randomization for treatment allocation were excluded from the analysis. Summary estimates on Overall survival (OS), Progression-free survival (PFS) and toxicity outcomes (grade 3–4 mucositis and neutropenia) were extracted from the included studies on a predefined database sheet. Bias was assessed through the Chocrane risk of bias assessment tool. We performed a set of pair-wise meta-analyses using a random effect model. We also performed a random effect network meta-analysis under a Bayesian framework. FindingsFrom the 57 included trials, including 15,723 patients, was possible to conduct analysis on 26 treatments for OS, 22 treatments for PFS and 10 treatments for toxicity. In terms of OS Concurrent chemoradiotherapy (CCRT) with cisplatin (HR 0.70, 95% CrI [credible interval] 0.62–0.78) and cetuximab on top of CCRT (HR 0.7, 95% CrI 0.5–0.97) are clearly superior to conventional RT alone. Induction chemotherapy (IC) with cisplatin and fluorouracil (HR 0.74, 95% CrI 0.52–0.95), IC with docetaxel, cisplatin, fluorouracil (HR 0.55, 95% CrI 0.54–0.89) and IC with paclitaxel, cisplatin, fluorouracil (HR 0.55, 95% CrI 0.34–0.89) before CCRT are all superior to conventional RT. CCRT with cisplatin is also superior to altered fractionation RT (HR 0.74, 95% CrI 0.64–0.84). Altered fractionation RT is not superior to conventional RT (HR 0.95, 95% CrI 0.85–1.06). Regarding PFS, CCRT with cisplatin (HR 0.72, 95% CrI 0.63–0.83), cisplatin and fluorouracil (HR 0.67, 95% CrI 0.5–0.88), carboplatin (HR 0.63, 95% CrI 0.46–0.87), carboplatin and fluorouracil (HR 0.75, 95% CrI 0.56–1), IC with cisplatin and fluorouracil (HR 0.59, 95% CrI 0.45–0.78), IC with docetaxel, cisplatin and fluorouracil (HR 0.53, 95% CrI 0.41–0.68) and IC with paclitaxel, cisplatin and fluorouracil (HR 0.59, 95% CrI 0.35–0.99) are superior to conventional RT and altered fractionation RT. IC with docetaxel, cisplatin and fluorouracil shows a significant superiority against CCRT with cisplatin (HR 0.73 95% CrI 0.58–0.92). Altered fractionation RT is not superior to conventional RT (HR 0.91, 95% CrI 0.81–1.02).Altered fractionation increases the risk of developing grade 3–4 mucositis compared to conventional RT (OR 3.74 95% 1.64–8.67) InterpretationCCRT with cisplatin remains the gold standard of treatment. Taxane based IC regimens may have a impact on locally advanced disease. Altered fractionation RT is inferior to CCRT and also does not seem to be meaningfully better than conventionally fractionated RT alone. Its role in locally advanced disease should be reevaluated.

Prognostic impact of HPV-associated p16-expression and smoking status on outcomes following radiotherapy for oropharyngeal cancer: The MARCH-HPV project

Background and purposeEvaluate the prognostic and predictive impact of HPV-associated p16-expression and assess the combined prognostic impact of p16 and smoking on altered fractionated radiotherapy (AFRT) for oropharyngeal cancer (OPC) within the frames of the update of the Meta-Analysis of Radiotherapy in Carcinomas of Head and neck (MARCH). Materials and methodsPatients with OPC, known tumor p16-status and smoking history were identified from the MARCH update, resulting in a dataset of 815 patients from four randomized trials (RTOG9003, DAHANCA6&7, RTOG0129, ARTSCAN). Analysis was performed using a Cox model stratified by trial and adjusted on gender, age, T-stage, N-stage, type of radiotherapy fractionation, p16, smoking. Primary endpoint was progression-free survival (PFS). ResultsIn total, 465 patients (57%) had p16-positive tumors and 350 (43%) p16-negative. Compared to p16-negative, p16-positive patients had significantly better PFS (HR = 0.42 [95% CI: 0.34–0.51], 28.9% absolute increase at 10 years) and OS (HR = 0.40 [0.32–0.49], 32.1% absolute increase at 10 years). No interaction between p16-status and fractionation schedule was detected. Smoking negatively impacted outcome; in the p16-positive subgroup, never smokers had significantly better PFS than former/current smokers (HR = 0.49 [0.33–0.75], 24.2% survival benefit at 10 years). ConclusionsNo predictive impact of p16-status on response to AFRT could be detected but the strong prognostic impact of p16-status was confirmed and especially p16-positive never smoking patients have superior outcome after RT.

Role of radiotherapy fractionation in head and neck cancers (MARCH): an updated meta-analysis

The Meta-Analysis of Radiotherapy in squamous cell Carcinomas of Head and neck (MARCH) showed that altered fractionation radiotherapy is associated with improved overall and progression-free survival compared with conventional radiotherapy, with hyperfractionated radiotherapy showing the greatest benefit. This update aims to confirm and explain the superiority of hyperfractionated radiotherapy over other altered fractionation radiotherapy regimens and to assess the benefit of altered fractionation within the context of concomitant chemotherapy with the inclusion of new trials. For this updated meta-analysis, we searched bibliography databases, trials registries, and meeting proceedings for published or unpublished randomised trials done between Jan 1, 2009, and July 15, 2015, comparing primary or postoperative conventional fractionation radiotherapy versus altered fractionation radiotherapy (comparison 1) or conventional fractionation radiotherapy plus concomitant chemotherapy versus altered fractionation radiotherapy alone (comparison 2). Eligible trials had to start randomisation on or after Jan 1, 1970, and completed accrual before Dec 31, 2010; had to have been randomised in a way that precluded prior knowledge of treatment assignment; and had to include patients with non-metastatic squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx undergoing first-line curative treatment. Trials including a non-conventional radiotherapy control group, investigating hypofractionated radiotherapy, or including mostly nasopharyngeal carcinomas were excluded. Trials were grouped in three types of altered fractionation: hyperfractionated, moderately accelerated, and very accelerated. Individual patient data were collected and combined with a fixed-effects model based on the intention-to-treat principle. The primary endpoint was overall survival. Comparison 1 (conventional fractionation radiotherapy vs altered fractionation radiotherapy) included 33 trials and 11 423 patients. Altered fractionation radiotherapy was associated with a significant benefit on overall survival (hazard ratio [HR] 0·94, 95% CI 0·90-0·98; p=0·0033), with an absolute difference at 5 years of 3·1% (95% CI 1·3-4·9) and at 10 years of 1·2% (-0·8 to 3·2). We found a significant interaction (p=0·051) between type of fractionation and treatment effect, the overall survival benefit being restricted to the hyperfractionated group (HR 0·83, 0·74-0·92), with absolute differences at 5 years of 8·1% (3·4 to 12·8) and at 10 years of 3·9% (-0·6 to 8·4). Comparison 2 (conventional fractionation radiotherapy plus concomitant chemotherapy versus altered fractionation radiotherapy alone) included five trials and 986 patients. Overall survival was significantly worse with altered fractionation radiotherapy compared with concomitant chemoradiotherapy (HR 1·22, 1·05-1·42; p=0·0098), with absolute differences at 5 years of -5·8% (-11·9 to 0·3) and at 10 years of -5·1% (-13·0 to 2·8). This update confirms, with more patients and a longer follow-up than the first version of MARCH, that hyperfractionated radiotherapy is, along with concomitant chemoradiotherapy, a standard of care for the treatment of locally advanced head and neck squamous cell cancers. The comparison between hyperfractionated radiotherapy and concomitant chemoradiotherapy remains to be specifically tested. Institut National du Cancer; and Ligue Nationale Contre le Cancer.

Radiation-Induced Oral Mucositis.

Radiation-induced oral mucositis (RIOM) is a major dose-limiting toxicity in head and neck cancer patients. It is a normal tissue injury caused by radiation/radiotherapy (RT), which has marked adverse effects on patient quality of life and cancer therapy continuity. It is a challenge for radiation oncologists since it leads to cancer therapy interruption, poor local tumor control, and changes in dose fractionation. RIOM occurs in 100% of altered fractionation radiotherapy head and neck cancer patients. In the United Sates, its economic cost was estimated to reach 17,000.00 USD per patient with head and neck cancers. This review will discuss RIOM definition, epidemiology, impact and side effects, pathogenesis, scoring scales, diagnosis, differential diagnosis, prevention, and treatment.

Radiation therapy for oropharyngeal squamous cell carcinoma: Executive summary of an ASTRO Evidence-Based Clinical Practice Guideline

PurposeTo present evidence-based guidelines for the treatment of oropharyngeal squamous cell carcinoma (OPSCC) with definitive or adjuvant radiation therapy (RT). Methods and materialsThe American Society for Radiation Oncology convened the OPSCC Guideline Panel to perform a systematic literature review investigating the following key questions: (1) When is it appropriate to add systemic therapy to definitive RT in the treatment of OPSCC? (2) When is it appropriate to deliver postoperative RT with and without systemic therapy following primary surgery for OPSCC? (3) When is it appropriate to use induction chemotherapy in the treatment of OPSCC? (4) What are the appropriate dose, fractionation, and volume regimens with and without systemic therapy in the treatment of OPSCC? ResultsPatients with stage IV and stage T3 N0-1 OPSCC treated with definitive RT should receive concurrent high-dose intermittent cisplatin. Patients receiving adjuvant RT following surgical resection for positive surgical margins or extracapsular extension should be treated with concurrent high-dose intermittent cisplatin, and individuals with these risk factors who are intolerant of cisplatin should not routinely receive adjuvant concurrent systemic therapy. Induction chemotherapy should not be routinely delivered to patients with OPSCC. For patients with stage IV and stage T3 N0-1 OPSCC ineligible for concurrent chemoradiation therapy, altered fractionation RT should be used. ConclusionThe successful management of OPSCC requires the collaboration of radiation, medical, and surgical oncologists. When high-level data are absent for clinical decision-making, treatment recommendations should incorporate patient values and preferences to arrive at the optimal therapeutic approach.

Role of altered fractionation radiotherapy schedules in head and neck squamous cell carcinoma: Rationale, evidence and clinical issues.

Role of altered fractionation radiotherapy schedules in head and neck squamous cell carcinoma: Rationale, evidence and clinical issues.

ED10.03 New Developments in Radiotherapy of Stage III NSCLC

ED10.03 New Developments in Radiotherapy of Stage III NSCLC

Quality of life and swallowing with standard chemoradiotherapy versus accelerated radiotherapy and panitumumab in locoregionally advanced carcinoma of the head and neck: A phase III randomised trial from the Canadian Cancer Trials Group (HN.6)

AimTo compare quality of life (QOL) between standard (SFX) chemoradiotherapy (arm A) and altered fractionation radiotherapy (AFX) with panitumumab (PMab; arm B). MethodsPatients with T any N + M0 or T3-4N0M0 squamous cell head-neck carcinoma were randomised to SFX (70 Gy/35/7 wks) plus cisplatin (100 mg/m2 IV × 3) versus AFX (70 Gy/35/6 wks) plus PMab (9 mg/kg IV × 3). QOL was collected at baseline, end of radiation therapy (RT) and 2, 4, 6, 12, 24 and 36 months post-RT using the Functional Assessment of Cancer Therapy Head and Neck (FACT-H&N), MD Anderson Dysphagia Index (MDADI) and SWAL-QOL. We hypothesised a 6-point more favourable change in FACT-H&N score from baseline to 1 year in arm B over arm A. ResultsAmong 320 patients, median follow-up was 46 (range: 0.1–64.3) months, median age 56, 84% male, Eastern Cooperative Oncology Group PS 0 (71%), 1 (29%). Primary site was oropharynx in 81% (p16+ 68%, p16− 16%, missing 16%). Baseline scores did not differ by arm (A/B): FACT-H&N 116.5/115, MDADI Global 83/77, SWAL-QOL General 67/68. At 1 year, no difference was seen between arms in FACT-H&N change from baseline: A −1.70, B −4.81, p = 0.194. Subscale change scores by arm were (A/B): last week RT, FACT-Physical (−11.6, −10, p = 0.049), MDADI Physical (−40.4, −33.9, p = 0.045), and SWAL-QOL Eating Duration (−61.2, −51.2, p = 0.02), Eating Desire (−53.3, −43.9, p = 0.031) and Mental Health (−42, −32.6, p = 0.009); 4 months, HN subscale (−7.7, −10, p = 0.014). No clinically important differences by arm were seen post-treatment. ConclusionsPMab with AFX did not durably improve QOL or swallowing as compared with SFX with cisplatin. Trial registrationClinicalTrials.gov: NCT00820248.

Radiobiological effects of cancer stem cell-targeting therapy in a head and neck cancer model

Introduction Cancer stem cells (CSC) represent a subpopulation of cells that are responsible for treatment failure. While altered fractionation radiotherapy is a powerful tool in head and neck cancer (HNC) treatment, CSCs require targeting therapy in order to be eradicated. All-trans-retinoic acid (ATRA) was shown to have cell cycle effects that sensitise CSC response to treatment. Purpose The aim of this work was to optimise HNC treatment using targeted therapies and to evaluate the effect of such agents on the tumour population as a whole. Materials and methods A Monte Carlo model was developed to grow a hypoxic HNC consisting of all lineages of cancer cells. The biological input parameters led to a pre-treatment CSC population of 5.9%. The Linear Quadratic model was employed to simulate radiotherapy. The effects of ATRA, namely differentiation, cell arrest and apoptosis were modelled, based on literature data. Results While the effect of differentiation was marginal, cell arrest induced by ATRA resulted in 14.4 Gy lower dose as compared to radiotherapy-alone for the same tumour response. The effect of apoptosis decreased the total dose needed for CSC eradication with a further 10.8 Gy. However, the tumour population as a whole was not notably affected, as the quiescent cells appear to dictate the shape of the survival curve. Conclusion ATRA exhibits a powerful effect on CSCs when combined with radiotherapy. Nevertheless, the model showed that quiescent cells should not be neglected, as their radioresistance is a potential threat if cells are recruited into the cell cycle.

How does altered fractionation radiotherapy affect outcomes in people with head and neck cancer?

How does altered fractionation radiotherapy affect outcomes in people with head and neck cancer?