Efficacy and toxicity of primary re-irradiation for malignant spinal cord compression based on radiobiological modelling: a phase II clinical trial.

BACKGROUND: The efficacy and safety of primary re-irradiation for MSCC are not known. Our aim was to establish the efficacy and safety of biologically effective dose-based re-irradiation. METHODS: Patients presenting with MSCC at a previously irradiated spine segment, and not proceeding with surgical decompression, were eligible. A 3 Gray per fraction experimental schedule (minimum 18 Gy/6 fractions, maximum 30 Gy/10 fractions) was used, delivering a maximum cumulative spinal dose of 100 Gy2 if the interval since the last radiotherapy was within 6 months, or 130 Gy2 if longer. The primary outcome was a change in mobility from week 1 to week 5 post-treatment, as assessed by the Tomita score. The RTOG SOMA score was used to screen for spinal toxicity, and an MRI performed to assess for radiation-induced myelopathy (RIM). RESULTS: Twenty-two patients were enroled, of whom eleven were evaluable for the primary outcome. Nine of eleven (81.8%) had stable or improved Tomita scores at 5 weeks. One of eight (12.5%) evaluable for late toxicity developed RIM. CONCLUSIONS: Re-irradiation is an efficacious treatment for MSCC. There is a risk of RIM with a cumulative dose of 120 Gy2. CLINICAL TRIAL REGISTRATION: Cancer Trials Ireland (ICORG 07-11); NCT00974168.

The impact of pre-treatment smoking status on survival after chemoradiotherapy for locally advanced non-small-cell lung cancer.

INTRODUCTION: Smoking is a risk factor for the development of lung cancer and reduces life expectancy within the general population. Retrospective studies suggest that non-smokers have better outcomes after treatment for lung cancer. We used a prospective database to investigate relationships between pre-treatment smoking status and survival for a cohort of patients with stage III non-small-cell lung cancer (NSCLC) treated with curative-intent concurrent chemoradiotherapy (CRT). METHODS: All patients treated with CRT for stage III NSCLC at a major metropolitan cancer centre were prospectively registered to a database. A detailed smoking history was routinely obtained at baseline. Kaplan-Meier statistics were used to assess overall survival and progression-free survival in never versus former versus current smokers. RESULTS: Median overall survival for 265 eligible patients was 2.21 years (95 % Confidence Interval 1.78, 2.84). It was 5.5 years (95 % CI 2.1, not reached) for 25 never-smokers versus 1.9 years (95 % CI 1.5, 2.7) for 182 former smokers and 2.2 years (95 % CI 1.3, 2.7) for 58 current smokers. Hazard ratio for death was 2.43 (95 % CI 1.32-4.50) for former smokers and 2.75 (95 % CI 1.40, 5.40) for current smokers, p = 0.006. Actionable tumour mutations (EGFR, ALK, ROS1) were present in more never smokers (14/25) than former (9/182) or current (3/58) smokers. TKI use was also higher in never smokers but this was not significantly associated with superior survival (Hazard ratio 0.71, 95 % CI 0.41, 1.26). CONCLUSIONS: Never smokers have substantially better overall survival than former or current smokers after undergoing CRT for NSCLC.

Validation of the bladder neck as an important organ at risk in prostate seed brachytherapy based on D2cc: A single-institution, retrospective review.

Purpose: International guidelines recommend urethral dose volume constraints to minimize the risk of urinary toxicity after prostate brachytherapy. An association between dose to the bladder neck (BN) and toxicity has previously been reported, and we sought to evaluate the impact of this organ at risk on urinary toxicity, based on intra-operative contouring. Material and methods: Rates of acute and late urinary toxicity (AUT and LUT, respectively) were graded according to CTCAE version 5.0 for 209 consecutive patients who underwent low-dose-rate (LDR) brachytherapy monotherapy, with approximately equal numbers treated before and after we began routinely contouring the BN. AUT and LUT were compared in patients treated before and after we began contouring the OAR, and also for those treated after we began contouring who had a D2cc of greater than or less than 50% prescription dose. Results: AUT and LUT fell after intra-operative BN contouring was instituted. Rates of grade ≥ 2 AUT fell from 15/101 (15%) to 9/104 (8.6%), p = 0.245. Grade ≥ 2 LUT decreased from 32/100 (32%) to 18/100 (18%), p = 0.034. Grade ≥ 2 AUT was observed in 4/63 (6.3%) and 5/34 (15%) of those with a BN D2cc >/≤ 50%, respectively, of prescription dose. Corresponding rates for LUT were 11/62 (18%) and 5/32 (16%). Conclusions: There were lower urinary toxicity rates for patients treated after we commenced routine intra-operative contouring of the BN. No clear relationship was observed between dosimetry and toxicity in our population.

Long-Term Follow-up of Patients Treated at a Single Institution Using a Passively Scattered Proton Beam; Observations Around the Occurrence of Second Malignancies.

PURPOSE: To investigate the occurrence of second malignancies resulting from the secondary radiation from a passively scattered proton beam. METHODS AND MATERIALS: A cohort of patients with long-term follow-up was defined. All were treated at the same institution with the same proton delivery system, consisting of a 200 MeV fixed, horizontal, passively scattered beam combined with a robotic chair. This setup allows for stereotactic positioning and permits fractionated treatments. The majority of patients underwent cranial or intracranial stereotactic radiation therapy. Patients with previous photon therapy or a follow-up of 24 months or less were excluded. For out-of-field secondary malignancies (SMs), the observed incidence in the study population was compared to the risk of developing a malignancy in the general population, taking patient sex into account. RESULTS: From September 1993 to May 2016, a total of 524 patients received proton beam therapy, and 322 patients could be evaluated for this study (164 female and 158 male). Age ranged from 2 to 85 years, with a median of 40 years. Follow-up ranged from 25 to 276 months, with a median of 150 months (12.5 years). During the study observation period, 7 patients had out-of-field new malignant disease. Three female patients developed a malignancy, compared with an expected incidence of 4.09 (standardized incidence ratio, 0.73 [95% confidence interval, 0.24-2.27]); 4 male patients developed a malignancy, versus an expected incidence of 3.99 (standardized incidence ratio, 1.00 [95% confidence interval, 0.38-2.67]). New intracranial disease developed in 9 patients: 8 meningiomas and 1 carcinoma. CONCLUSIONS: For out-of-field SMs, no increased risk of developing a variety of malignancies was observed. For in-field SMs, only 1 malignant histology was noted 15 years after the original proton therapy. No SM was observed in children and young adults.