A modelled comparison of prostate cancer control rates after high-dose-rate brachytherapy (3145 multicentre patients) combined with, or in contrast to, external-beam radiotherapy.

Background And Purpose: To analyse biochemical relapse-free-survival results for prostate cancer patients receiving combined external beam and high-dose-rate brachytherapy, in comparison with expected results using projections based on dose/fractionation/response parameter values deduced from a previous external-beam-alone 5969-patient multicentre dataset.

Material And Methods: Results on a total of 3145 prostate cancer patients receiving brachytherapy (BT) as part or all of their treatment were collected from 10 institutions, and subjected to linear-quadratic (LQ) modelling of dose response and fractionation parameters.

Results: Treatments with BT components of less than 25Gy, 3-4 BT fractions, doses per BT fraction up to 6Gy, and treatment times of 3-7weeks, all gave outcomes expected from LQ projections of the external-beam-alone data (α/β=1.

What would be the most appropriate α/β ratio in the setting of stereotactic body radiation therapy for early stage non-small cell lung cancer.

We hypothesize that the correlation between the radiation dose expressed as the biologically effective dose (BED) and the clinical endpoints will correlate better as the value of the α/β ratio is increased to >10 Gy, which theoretically minimizes the overestimation of the dose potency associated with the linear quadratic (LQ) formula in the setting of stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC). A search was conducted in the PubMed electronic databases in August 2011. In the studies analyzed, increasing the α/β ratio is associated with an increase in the strength of the correlation between isocenter BED and local control, especially in the studies with median followup of ≥24 months, for which Spearman's correlation coefficients of 0.

Is the α/β ratio for prostate tumours really low and does it vary with the level of risk at diagnosis?

Aim: To answer the questions: Is the α/β ratio (radiosensitivity to size of dose-per-fraction) really low enough to justify using a few large dose fractions instead of the traditional many small doses? Does this parameter vary with prognostic risk factors?

Methods And Materials: Three large statistical overviews are critiqued, with results for 5,000, 6,000 and 14,000 patients with prostate carcinoma, respectively.

Results: These major analyses agree in finding the average α/β ratio to be less than 2 Gy: 1.55, (95% confidence interval=0.

Revising the radiobiological model of synchronous chemotherapy in head-and-neck cancer: a new analysis examining reduced weighting of accelerated repopulation.

Purpose: Previous studies of synchronous chemoradiation therapy have modeled the additional effect of chemotherapy as additional radiation therapy biologically effective dose (BED). Recent trials of accelerated versus conventional fractionation chemoradiation have cast doubt on such modeling. The purpose of this study was to identify alternative models.

Effect of fractionation in stereotactic body radiation therapy using the linear quadratic model.

Purpose: To examine the fractionation effect of stereotactic body radiation therapy with a heterogeneous dose distribution.

Methods: Derived from the linear quadratic formula with measurements from a hypothetical 2-cm radiosurgical tumor, the threshold percentage was defined as (α/β(tissue)/α/β(tumor)), the balance α/β ratio was defined as (prescription dose/tissue tolerance*α/β(tumor)), and the balance dose was defined as (tissue tolerance/threshold percentage).

Results: With increasing fractions and equivalent peripheral dose to the target, the biological equivalent dose of "hot spots" in a target decreases.

A Comment on Qi et al.: An Estimation of Radiobiological Parameters for Head-and-Neck and the Clinical Implications. Cancers, 2012, 4, 566-580.

Important results were shown as cell survival points in the two panels of the figure which is reproduced in this Comment letter. A curve was fitted assuming the mono-exponential recovery half-time of 17 ± 21 minutes. The wide error limits indicate that this fit is not very good, but the notable feature of both panels is that the last four points are clearly continuing to rise, above the "fitted" curve.

Later outcomes and alpha/beta estimate from hypofractionated conformal three-dimensional radiotherapy versus standard fractionation for localized prostate cancer.

Purpose: Now that the follow-up time has exceeded 5 years, an estimate of the α/β ratio can be presented. The additional late outcomes in patients treated with three-dimensional conformal external beam radiotherapy for localized prostate cancer using a hypofractionated vs. a standard fractionation regimen are reported from this prospective nonrandomized contemporary comparison.

Reirradiation human spinal cord tolerance for stereotactic body radiotherapy.

Purpose: We reviewed the treatment for patients with spine metastases who initially received conventional external beam radiation (EBRT) and were reirradiated with 1-5 fractions of stereotactic body radiotherapy (SBRT) who did or did not subsequently develop radiation myelopathy (RM).

Methods And Materials: Spinal cord dose-volume histograms (DVHs) for 5 RM patients (5 spinal segments) and 14 no-RM patients (16 spine segments) were based on thecal sac contours at retreatment. Dose to a point within the thecal sac that receives the maximum dose (P(max)), and doses to 0.

Hypofractionated versus conventionally fractionated radiotherapy for prostate carcinoma: final results of phase III randomized trial.

Purpose: To evaluate the long-term efficacy and toxicity of a hypofractionated (55 Gy in 20 fractions within 4 weeks) vs. a conventionally fractionated (64 Gy in 32 fractions within 6.5 weeks) dose schedule for radiotherapy (RT) for localized carcinoma of the prostate.

Characteristics of response of oral and pharyngeal mucosa in patients receiving chemo-IMRT for head and neck cancer using hypofractionated accelerated radiotherapy.

Purpose: This study describes the acute response of oral and pharyngeal mucosa to chemo-IMRT schedules using different doses per fraction.

Materials And Methods: Patients, treated in prospective trials of concomitant chemo-IMRT with 2.17 Gy, 2.

Stereotactic body radiation therapy in non-small-cell lung cancer: linking radiobiological modeling and clinical outcome.

For patients with peripheral, early-stage non-small-cell lung cancer, it has been found feasible to deliver 5 or fewer fractions of large doses through stereotactic body radiation therapy (SBRT) without causing severe early or late injury and with impressive tumor control. In this review, we employ radiobiological modeling with the linear quadratic formulation to explore the adequacy of various dose schedules used for tumor control in the lung as supported by clinical evidence, the influence of dose distribution and delivery time on local control, and how to decrease the likelihood of severe toxicity following SBRT. Furthermore, the validity of the linear quadratic formalism in the high dose range of SBRT for lung cancer is explored.

A phase I/II radiation dose escalation study with concurrent chemotherapy for patients with inoperable stages I to III non-small-cell lung cancer: phase I results of RTOG 0117.

Purpose: In preparation for a Phase III comparison of high-dose versus standard-dose radiation therapy, this Phase I/II study was initiated to establish the maximum tolerated dose of radiation therapy in the setting of concurrent chemotherapy, using three-dimensional conformal radiation therapy for non-small-cell lung cancer.

Methods And Materials: Eligibility included patients with histologically proven, unresectable Stages I to III non-small-cell lung cancer. Concurrent chemotherapy consisted of paclitaxel, 50 mg/m(2), and carboplatin, AUC of 2, given weekly.

Acute and late toxicity in a randomized trial of conventional versus hypofractionated three-dimensional conformal radiotherapy for prostate cancer.

Purpose: To compare the toxicity between hypofractionation vs. conventional fractionation schedules in patients with high-risk prostate cancer.

Methods And Materials: Between January 2003 and December 2007, 168 patients were randomized to receive either hypofractionated (62 Gy in 20 fractions within 5 weeks, 4 fractions/wk) or conventionally fractionated (80 Gy in 40 fractions within 8 weeks) three-dimensional conformal radiotherapy to the prostate and seminal vesicles.

Red shell: defining a high-risk zone of normal tissue damage in stereotactic body radiation therapy.

Purpose: To define a volume of tissue just outside of the clinical target volume (CTV) or planning target volume (PTV) in stereotactic body radiation therapy (SBRT) that receives doses appreciably above the tolerance level and in which other critical tissue structures must be avoided.

Methods And Materials: We define the tissue between the borders of the CTV and PTV as the Inner Red Shell. The tissue surrounding the PTV that receives higher than the local tissue tolerance is defined as the Outer Red Shell.

Primary analysis of the phase II component of a phase I/II dose intensification study using three-dimensional conformal radiation therapy and concurrent chemotherapy for patients with inoperable non-small-cell lung cancer: RTOG 0117.

Purpose: Phase I of Radiation Therapy Oncology Group (RTOG) 0117 determined that 74 Gy was the maximum-tolerated dose with concurrent weekly carboplatin/paclitaxel chemotherapy for inoperable non-small-cell lung cancer (NSCLC). Phase II results are reported here. PATIENTS AND METHODS Patients with unresectable stages I-III NSCLC were eligible.

Stereotactic body radiation therapy for inoperable early stage lung cancer.

Context: Patients with early stage but medically inoperable lung cancer have a poor rate of primary tumor control (30%-40%) and a high rate of mortality (3-year survival, 20%-35%) with current management.

Objective: To evaluate the toxicity and efficacy of stereotactic body radiation therapy in a high-risk population of patients with early stage but medically inoperable lung cancer.

Design, Setting, And Patients: Phase 2 North American multicenter study of patients aged 18 years or older with biopsy-proven peripheral T1-T2N0M0 non-small cell tumors (measuring <5 cm in diameter) and medical conditions precluding surgical treatment.

A prospective phase III randomized trial of hypofractionation versus conventional fractionation in patients with high-risk prostate cancer.

Purpose: To compare the toxicity and efficacy of hypofractionated (62 Gy/20 fractions/5 weeks, 4 fractions per week) vs. conventional fractionation radiotherapy (80 Gy/40 fractions/8 weeks) in patients with high-risk prostate cancer.

Methods And Materials: From January 2003 to December 2007, 168 patients were randomized to receive either hypofractionated or conventional fractionated schedules of three-dimensional conformal radiotherapy to the prostate and seminal vesicles.

Spinal cord tolerance for stereotactic body radiotherapy.

Purpose: Dosimetric data are reported for five cases of radiation-induced myelopathy after stereotactic body radiotherapy (SBRT) to spinal tumors. Analysis per the biologically effective dose (BED) model was performed.

Methods And Materials: Five patients with radiation myelopathy were compared to a subset of 19 patients with no radiation myelopathy post-SBRT.