The role of postoperative chemoradiation for oropharynx carcinoma: A critical appraisal revisited.

A recent review in this Journal, which criticizes NCCN’s recommendations based, in part, on the RTOG 9501 and the EORTC 22931 trials, warrants comment. We herein provide additional data addressing many of the points and misinterpretations raised in that review which convincingly supports the use of concomitant chemotherapy and radiotherapy in patients with good performance status and high-risk pathologic features after surgery for mucosal head and neck squamous cell carcinoma.

Retinoblastoma and phosphate and tensin homolog tumor suppressors: impact on ductal carcinoma in situ progression.

Background: A subset of patients with ductal carcinoma in situ (DCIS) will progress to invasive breast cancer. However, there are currently no markers to differentiate women at high risk from those at lower risk of developing invasive disease.

Methods: The association of two major tumor suppressor genes, retinoblastoma (RB) and phosphatase and tensin homolog (PTEN), with risk of any ipsilateral breast event (IBE) or progression to invasive breast cancer (IBC) was analyzed using data from 236 DCIS patients treated with breast conserving surgery with long-term follow-up.

Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer.

Purpose: To report the long-term results of the Intergroup Radiation Therapy Oncology Group 91-11 study evaluating the contribution of chemotherapy added to radiation therapy (RT) for larynx preservation.

Patients And Methods: Patients with stage III or IV glottic or supraglottic squamous cell cancer were randomly assigned to induction cisplatin/fluorouracil (PF) followed by RT (control arm), concomitant cisplatin/RT, or RT alone. The composite end point of laryngectomy-free survival (LFS) was the primary end point.

Long-term follow-up of the RTOG 9501/intergroup phase III trial: postoperative concurrent radiation therapy and chemotherapy in high-risk squamous cell carcinoma of the head and neck.

Purpose: Previous analysis of this Intergroup trial demonstrated that with a median follow-up among surviving patients of 45.9 months, the concurrent postoperative administration of cisplatin and radiation therapy improved local-regional control and disease-free survival of patients who had high-risk resectable head-and-neck carcinomas. With a minimum of 10 years of follow-up potentially now available for all patients, these results are updated here to examine long-term outcomes.

Hyperfractionated or accelerated radiotherapy for head and neck cancer.

Background: Several trials have studied the role of altered fractionation radiotherapy in head and neck squamous cell carcinoma, but the effect of such treatment on survival is not clear.

Objectives: The aim of this individual patient data (IPD) meta-analysis was to assess whether this type of radiotherapy could improve survival.

Search Strategy: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; CENTRAL (2010, Issue 3); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ISRCTN and additional sources for published and unpublished trials.

Validation of lysyl oxidase as a prognostic marker for metastasis and survival in head and neck squamous cell carcinoma: Radiation Therapy Oncology Group trial 90-03.

Purpose: To validate lysyl oxidase (LOX), a hypoxia-related protein, as a marker for metastasis in an independent head and neck cancer (HNC) patient group enrolled onto a prospective trial.

Patients And Methods: We performed traditional immunohistochemical (IHC) staining and automated quantitative analysis (AQUA) for LOX expression in 66 HNC patients from one institution. We also performed AQUA staining for LOX in 306 of 1,113 patients treated on a phase III trial comparing four radiation fractionation schedules in locally advanced HNC (RTOG 90-03).

Surrogate endpoints for overall survival in locally advanced head and neck cancer: meta-analyses of individual patient data.

Background: The gold standard endpoint in randomised trials of locally advanced head and neck squamous-cell carcinoma (HNSCC) is overall survival. Our objective was to study whether duration of locoregional control or event-free survival (EFS) could be considered as surrogate endpoints to estimate the effect of radiotherapy and chemotherapy on overall survival. This would allow a reduction in the duration and cost of the development of new treatments.

Emotional well-being does not predict survival in head and neck cancer patients: a Radiation Therapy Oncology Group study.

Background: The objective of the current study was to examine whether emotional well-being predicted survival in a large sample of patients with head and neck cancer who were participating in multicenter clinical trials.

Methods: Participants were enrolled in 2 Radiation Oncology Group (RTOG) clinical trials (RTOG 9003 and RTOG 9111) and completed a baseline measure of quality of life (the Functional Assessment of Cancer Therapy-General [FACT-G]), which included an Emotional Well-Being subscale. The outcome measure was overall survival.

Pretreatment quality of life predicts for locoregional control in head and neck cancer patients: a radiation therapy oncology group analysis.

Purpose: To analyze the prospectively collected health-related quality-of-life (HRQOL) data from patients enrolled in two Radiation Therapy Oncology Group randomized Phase III head and neck cancer trials (90-03 and 91-11) to assess their value as an independent prognostic factor for locoregional control (LRC) and/or overall survival (OS).

Methods And Materials: HRQOL questionnaires, using a validated instrument, the Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N), version 2, were completed by patients before the start of treatment. OS and LRC were the outcome measures analyzed using a multivariate Cox proportional hazard model.

Microvessel density >or=60 does not predict for outcome after radiation treatment for locally advanced head and neck squamous cell carcinoma: results of a correlative study from the Radiation Therapy Oncology Group (RTOG) 90-03 Trial.

Objectives: To assess whether microvessel density (MVD), an immunohistochemical marker for tumor vascularity, predicts for radiotherapy (RT) outcome in locally advanced HNSCC patients.

Methods: A total of 459 patients, enrolled on the RTOG 90-03 trial, had biopsy specimens submitted, and a value for MVD determined, prior to definitive RT. 450 patients were analyzable for this study.

Radiotherapy with or without erythropoietin for anemic patients with head and neck cancer: a randomized trial of the Radiation Therapy Oncology Group (RTOG 99-03).

Purpose: To determine whether the addition of recombinant human erythropoietin (Epo) could improve the outcomes of anemic patients receiving definitive radiotherapy for squamous cell carcinoma of the head and neck (SCCHN).

Methods And Materials: Eligible patients had SCCHN, with a plan for continuous-course definitive radiotherapy (66-72 Gy) with or without chemotherapy. Patients with Stage III or IV SCCHN were required to undergo concurrent chemoradiotherapy and/or accelerated fractionation radiotherapy.

TAME: development of a new method for summarising adverse events of cancer treatment by the Radiation Therapy Oncology Group.

Background: We aimed to examine deficiencies in established methods of summarising adverse events, and to create a new reporting system (TAME) for summarising the toxicity burden of cancer treatment. TAME consolidates traditional adverse-event data into three risk domains: short-term (acute) Toxicity (T), Adverse long-term (late) effects (A), and Mortality risk (M) generated by a treatment programme (E=End results); and assigns treatments to risk classes for each risk domain.

Methods: We examined formally an established method for summarising adverse events (the max-grade method) in five trials of patients with head and neck cancer done between September, 1991, and August, 2000, by the Radiation Therapy Oncology Group (RTOG) that involved 13 treatment groups (2304 patients).

Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis.

Background: Several trials have studied the role of unconventional fractionated radiotherapy in head and neck squamous cell carcinoma, but the effect of such treatment on survival is not clear. The aim of this meta-analysis was to assess whether this type of radiotherapy could improve survival.

Methods: Randomised trials comparing conventional radiotherapy with hyperfractionated or accelerated radiotherapy, or both, in patients with non-metastatic HNSCC were identified and updated individual patient data were obtained.

Disadvantage of men living alone participating in Radiation Therapy Oncology Group head and neck trials.

Purpose: This study evaluated whether males without partners were disadvantaged for survival in Radiation Therapy Oncology Group (RTOG) head and neck cancer clinical trials.

Methods: Patients treated on three RTOG trials were studied. The Cox proportional hazards model was used to determine if sex and the interaction between sex and marital/partner status were independent prognostic variables for overall survival controlling for Karnofsky performance status, tumor stage, nodal stage, primary site, and protocol treatment.

Randomized phase III trial of low-dose isotretinoin for prevention of second primary tumors in stage I and II head and neck cancer patients.

Background: Isotretinoin (13-cis-retinoic acid) is a synthetic vitamin A derivative, or retinoid, widely used in the treatment of cystic acne. Preclinical and clinical studies of high-dose isotretinoin in patients with head and neck squamous cell cancer (HNSCC) have produced encouraging results. We conducted a phase III randomized trial of low-dose isotretinoin versus placebo in early-stage HNSCC patients to assess its effect on second primary tumor incidence and survival.

Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck.

Background: Despite the use of resection and postoperative radiotherapy, high-risk squamous-cell carcinoma of the head and neck frequently recurs in the original tumor bed. We tested the hypothesis that concurrent postoperative administration of cisplatin and radiotherapy would improve the rate of local and regional control.

Methods: Between September 9, 1995, and April 28, 2000, 459 patients were enrolled.

A multinational, randomized phase III trial of iseganan HCl oral solution for reducing the severity of oral mucositis in patients receiving radiotherapy for head-and-neck malignancy.

Purpose: Oral mucositis (OM) causes significant morbidity during the course of radiotherapy (RT) treatment of head-and-neck cancer. It is hypothesized that infection plays a role in the development of OM. We tested the efficacy of iseganan HCl (iseganan), a synthetic peptide with broad-spectrum antimicrobial activity, for preventing RT-associated OM.

Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer.

Background: Induction chemotherapy with cisplatin plus fluorouracil followed by radiotherapy is the standard alternative to total laryngectomy for patients with locally advanced laryngeal cancer. The value of adding chemotherapy to radiotherapy and the optimal timing of chemotherapy are unknown.

Methods: We randomly assigned patients with locally advanced cancer of the larynx to one of three treatments: induction cisplatin plus fluorouracil followed by radiotherapy, radiotherapy with concurrent administration of cisplatin, or radiotherapy alone.

Phase III trial of long-term adjuvant androgen deprivation after neoadjuvant hormonal cytoreduction and radiotherapy in locally advanced carcinoma of the prostate: the Radiation Therapy Oncology Group Protocol 92-02.

Purpose: Radiation Therapy Oncology Group (RTOG) Protocol 92-02 was a randomized trial testing long-term (LT) adjuvant androgen deprivation (AD) after initial AD with external-beam radiotherapy (RT) in patients with locally advanced prostate cancer (PC; T2c-4) and with prostate-specific antigen level less than 150 ng/mL.

Patients And Methods: Patients received a total of 4 months of goserelin and flutamide, 2 months before and 2 months during RT. A radiation dose of 65 to 70 Gy was given to the prostate and a dose of 44 to 50 Gy to the pelvic lymph nodes.

Tissue micro-array: a cost and time-effective method for correlative studies by regional and national cancer study groups.

Tissue micro-arrays have been used for molecular and immunohistochemical studies. We sought to evaluate whether such arrays could substitute for whole sections in correlative studies performed by the Radiation Therapy Oncology Group. Four multitumor 150-sample arrays were built using formalin-fixed, paraffin-embedded, archival prostate, brain, and head/neck tumor blocks from RTOG tissue bank.

INT 0123 (Radiation Therapy Oncology Group 94-05) phase III trial of combined-modality therapy for esophageal cancer: high-dose versus standard-dose radiation therapy.

Purpose: To compare the local/regional control, survival, and toxicity of combined-modality therapy using high-dose (64.8 Gy) versus standard-dose (50.4 Gy) radiation therapy for the treatment of patients with esophageal cancer.