Preoperative Radiotherapy with a Simultaneous Integrated Boost Compared to Chemoradiotherapy for cT3-4 Rectal Cancer: Long-Term Results of a Multicenter Randomized Study.

BACKGROUND: Preoperative chemoradiotherapy (CRT) is the standard treatment for T3-4 rectal cancer. Here, we compared image-guided and intensity-modulated RT (IG-IMRT) with a simultaneous integrated boost (SIB) (instead of concomitant chemotherapy) versus CRT in a multi-centric randomized trial. METHODS: cT3-4 rectal cancer patients were randomly assigned to receive preoperative IG-IMRT 46 Gy/23 fractions plus capecitabine 825 mg/m² twice daily (CRT arm) or IG-IMRT 46 Gy/23 fractions with an SIB to the rectal tumor up to a total dose of 55.2 Gy (RTSIB arm). RESULTS: A total of 174 patients were randomly assigned between April 2010 and May 2014. Grade 3 acute toxicities were 6% and 4% in the CRT and RTSIB arms, respectively. The mean fractional change in SUVmax at 5 weeks after completion of preoperative RT were -55.8% (±24.0%) and -52.9% (±21.6%) for patients in the CRT arm and RTSIB arm, respectively (p = 0.43). The pathologic complete response rate was 24% with CRT compared to 14% with RTSIB. There were no differences in 5-year overall survival (OS), progression-free survival (PFS) or local control (LC). CONCLUSIONS: The preoperative RTSIB approach was not inferior to CRT in terms of metabolic response, toxicity, OS, PFS and LC, and could be considered an available option for patients unfit for fluorouracil-based CRT.

Results of a multicenter study investigating the potential impact of the overall treatment time on outcomes of radiation therapy alone with 5×4 Gy for metastatic epidural spinal cord compression.

PURPOSE/OBJECTIVE: A 5×4 Gy program is commonly used for metastatic epidural spinal cord compression (MESCC). It is unclear whether an overall treatment time (OTT) of 5 days (5 consecutive fractions) results in better outcomes than an OTT of 7 days (ie, no irradiation during the weekend). METHODS AND MATERIALS: A total of 111 patients who received 5×4 Gy over 5 consecutive days were retrospectively compared with 277 patients treated with 5×4 Gy over 7 days (no irradiation during the weekend) for effect on motor function, local control of MESCC, and overall survival (OS). Ten further characteristics were evaluated: age, gender, interval tumor diagnosis to MESCC, visceral metastases, other bone metastases, primary tumor type, time developing motor deficits, walking ability, vertebrae involved, and performance status. RESULTS: On multivariate analysis regarding post-radiation therapy motor function, primary tumor type (P = .011) and time developing motor weakness (P < .001) were significant, whereas the OTT did not even achieve significance on univariate analysis (P = .99). On multivariate analysis of local control, visceral metastases (P = .006) were significant. Again, the OTT was not even significant on univariate analysis (P = .81). On multivariate analysis of OS, interval tumor diagnosis to MESCC (P = .015), visceral metastases (P .001), tumor type (P = .003), walking ability (P < .001), and Eastern Cooperative Oncology Group performance score (P < .001) achieved significance. Even on univariate analysis, OTT did not have an effect on OS (P = .79). CONCLUSIONS: Longer OTT did not impair outcomes of irradiation with 5×4 Gy for MESCC; thus, no compensation (for example an additional radiation fraction) is necessary if the radiation treatment is not continued during the weekend.

Optimal differentiation of high- and low-grade glioma and metastasis: a meta-analysis of perfusion, diffusion, and spectroscopy metrics.

INTRODUCTION: To perform a meta-analysis of advanced magnetic resonance imaging (MRI) metrics, including relative cerebral blood volume (rCBV), normalized apparent diffusion coefficient (nADC), and spectroscopy ratios choline/creatine (Cho/Cr) and choline/N-acetyl aspartate (Cho/NAA), for the differentiation of high- and low-grade gliomas (HGG, LGG) and metastases (MTS). METHODS: For systematic review, 83 articles (dated 2000-2013) were selected from the NCBI database. Twenty-four, twenty-two, and eight articles were included respectively for spectroscopy, rCBV, and nADC meta-analysis. In the meta-analysis, we calculated overall means for rCBV, nADC, Cho/Cr (short TE-from 20 to 35 ms, medium-from 135 to 144 ms), and Cho/NAA for the HGG, LGG, and MTS groups. We used random effects model to obtain weighted averages and select thresholds. RESULTS: Overall means (with 95% CI) for rCBV, nADC, Cho/Cr (short and medium echo time, TE), and Cho/NAA were: for HGG 5.47 (4.78-6.15), 1.38 (1.16-1.60), 2.40 (1.67-3.13), 3.27 (2.78-3.77), and 4.71 (3.24-6.19); for LGG 2.00 (1.71-2.28), 1.61 (1.36-1.87), 1.46 (1.20-1.72), 1.71 (1.49-1.93), and 2.36 (1.50-3.23); for MTS 5.06 (3.85-6.27), 1.35 (1.06-1.64), 1.89 (1.72-2.06), 3.14 (1.57-4.72), (Cho/NAA was not available). LGG had significantly lower rCBV, Cho/Cr, and Cho/NAA values than HGG or MTS. No significant differences were found for nADC. CONCLUSIONS: Best differentiation between HGG and LGG is obtained from rCBV, Cho/Cr, and Cho/NAA metrics. MTS could not be reliably distinguished from HGG by the methods investigated.

Radiotherapy With 4 Gy × 5 Versus 3 Gy × 10 for Metastatic Epidural Spinal Cord Compression: Final Results of the SCORE-2 Trial (ARO 2009/01).

PURPOSE: To compare short-course radiotherapy (RT) (4 Gy × 5) to longer-course RT (3 Gy × 10) for metastatic epidural spinal cord compression (MESCC). PATIENTS AND METHODS: Two-hundred three patients with MESCC and poor to intermediate expected survival were randomly assigned to 4 Gy × 5 in 1 week (n = 101) or 3 Gy × 10 in 2 weeks (n = 102). Patients were stratified according to ambulatory status, time developing motor deficits, and primary tumor type. Seventy-eight and 77 patients, respectively, were evaluable for the primary end point, 1-month overall response regarding motor function defined as improvement or no further progression of motor deficits. Other study end points included ambulatory status, local progression-free survival, and overall survival. End points were evaluated immediately after RT and at 1, 3, and 6 months thereafter. RESULTS: At 1 month, overall response rates regarding motor function were 87.2% after 4 Gy × 5 and 89.6% after 3 Gy × 10 (P = .73). Improvement rates were 38.5% and 44.2%, respectively, no further progression rates 48.7% and 45.5%, respectively, and deterioration rates 12.8% and 10.4%, respectively (P = .44). Ambulatory rates at 1 month were 71.8% and 74.0%, respectively (P = .86). At other times after RT, the results were also not significantly different. Six-month local progression-free survival was 75.2% after 4 Gy × 5 and 81.8% after 3 Gy × 10 (P = .51); 6-month overall survival was 42.3% and 37.8% (P = .68). CONCLUSION: Short-course RT with 4 Gy × 5 was not significantly inferior to 3 Gy × 10 in patients with MESCC and poor to intermediate expected survival.

Optimization by visualization of indices.

BACKGROUND AND PURPOSE: Physical 3D treatment planning provides a pool of parameters describing dose distributions. It is often useful to define conformal indices to enable quicker evaluation. However, the application of individual indices is controversial and not always effective. The aim of this study was to design a quick check of dose distributions based on several indices detecting underdosages within planning target volumes (PTVs) and overdosages in normal tissue. MATERIALS AND METHODS: Dose distributions of 215 cancer patients were considered. Treatment modalities used were three-dimensional conformal radiotherapy (3DCRT), radiosurgery, intensity-modulated radiotherapy (IMRT), intensity-modulated arc therapy (IMAT) and tomotherapy. The volumes recommended in ICRU 50 and 83 were used for planning and six conformation and homogeneity indices were selected: CI, CN, CICRU, COV, C∆, and HI. These were based on the PTV, the partial volume covered by the prescribed isodose (PI; PTVPI), the treated volume (TVPI), near maximum D2 and near minimum D98. Results were presented as a hexagon-the corners of which represent the values of the indices-and a modified test function F (Rosenbrock's function) was calculated. Results refer to clinical examples and mean values, in order to allow evaluation of the power of F and hexagon-based decision support procedures in detail and in general. RESULTS: IMAT and tomotherapy showed the best values for the indices and the lowest standard deviation followed by static IMRT. DCRT and radiosurgery (e.g. CN: IMAT 0.85 ± 0.06; tomotherapy 0.84 ± 0.06; IMRT 0.83 ± 0.07; 3DCRT 0.65 ± 0.08; radiosurgery 0.64 ± 0.11). In extreme situations, not all indices reflected the situation correctly. Over- and underdosing of PTV and normal tissue could be qualitatively assessed from the distortion of the hexagon in graphic analysis. Tomotherapy, IMRT, IMAT, 3DCRT and radiosurgery showed increasingly distorted hexagons, the type of distortion indicating exposure of normal tissue volumes. The calculated F values correlated with these observations. CONCLUSION: An evaluation of dose distributions cannot be based on a single conformal index. A solution could be the use of several indices presented as a hexagonal graphic and/or as a test function.

A randomized hypofractionation dose escalation trial for high risk prostate cancer patients: interim analysis of acute toxicity and quality of life in 124 patients.

BACKGROUND: The α/ß ratio for prostate cancer is postulated being in the range of 0.8 to 2.2 Gy, giving rise to the hypothesis that there may be a therapeutic advantage to hypofractionation. To do so, we carried out a randomized trial comparing hypofractionated and conventionally fractionated image-guided intensity modulated radiotherapy (IG-IMRT) in high-risk prostate cancer. Here, we report on acute toxicity and quality of life (QOL) for the first 124 randomized patients. METHODS: The trial compares 76 Gy in 38 fractions (5 fractions/week) (Arm 1) to 63 Gy in 20 fractions (4 fractions/week) (Arm 2) (IG-IMRT). Prophylactic pelvic lymph node irradiation with 46 Gy in 23 fractions sequentially (Arm 1) and 44 Gy in 20 fractions simultaneously (Arm 2) was applied. All patients had long term androgen deprivation therapy (ADT) started before RT. Both physician-rated acute toxicity and patient-reported QOL using EPIC questionnaire are described. RESULTS: There were no differences in overall maximum acute gastrointestinal (GI) or genitourinary (GU) toxicity. Compared to conventional fractionation (Arm 1), GI and GU toxicity both developed significantly earlier but also disappeared earlier in the Arm 2, reaching significant differences from Arm 1 at week 8 and 9. In multivariate analyses, only parameter shown to be related to increased acute Grade ≥1 GU toxicity was the study Arm 2 (p = 0.049). There were no statistically significant differences of mean EPIC scores in any domain and sub-scales. The clinically relevant decrease (CRD) in EPIC urinary domain was significantly higher in Arm 2 at month 1 with a faster recovery at month 3 as compared to Arm 1. CONCLUSIONS: Hypofractionation at 3.15 Gy per fraction to 63 Gy within 5 weeks was well tolerated. The GI and GU physician-rated acute toxicity both developed earlier but recovered faster using hypofractionation. There was a correlation between acute toxicity and bowel and urinary QOL outcomes. Longer follow-up is needed to determine the significance of these associations with late toxicity.

Treatment of hemorrhagic radiation-induced proctopathy with a 4% formalin application under perianal anesthetic infiltration.

AIM: To evaluate the results of hemorrhagic radiation proctopathy treatment with a 4% formalin application. METHODS: A prospective study was performed. Over a three-year period, 38 patients underwent 4% formalin application under perianal anesthetic infiltration for hemorrhagic radiation proctopathy. All patients included in the study were irradiated for prostate cancer. The patients ranged in age from 56-77 years (average 70 ± 5 years). All of the patients were referred for formalin therapy after noninvasive management had failed. Twenty-four (63.2%) patients underwent a single application, 10 (26.3%) patients underwent 2 applications, and 4 (10.5%) patients underwent 3 applications. RESULTS: Two to 36 mo (average 12 ± 3 mo) following treatment, 34 patients were interviewed (four were lost to follow-up). Twenty (58.8%) subjects reported complete cure, 8 (23.5%) subjects reported significant improvement, and 6 (17.7%) subjects reported no change. One patient (who underwent a colostomy at a regional hospital with no specialized services available for previous bleeding episodes from radiation proctopathy) was cured, and the colostomy was closed. One patient (2.6%) developed rectal mucosal damage after the second application. CONCLUSION: A 4-min application of 4% formalin for hemorrhagic radiation-induced proctopathy under perianal anesthetic infiltration in patients who have received external radial radiation therapy for prostate cancer is simple, reasonably safe, inexpensive, generally well tolerated, and effective.

A randomized trial comparing hypofractionated and conventionally fractionated three-dimensional external-beam radiotherapy for localized prostate adenocarcinoma : a report on acute toxicity.

PURPOSE: To compare acute gastrointestinal (GI) and genitourinary (GU) toxicity between patient groups with localized prostate adenocarcinoma, treated with conventionally fractionated (CFRT) and hypofractionated (HFRT) three-dimensional conformal external-beam radiotherapy (3D-CRT). PATIENTS AND METHODS: 91 patients were enrolled into a randomized study with a minimum follow-up of 3 months. 44 men in the CFRT arm were irradiated with 74 Gy in 37 fractions at 2 Gy per fraction for 7.5 weeks. 47 men in the HFRT arm were treated with 57 Gy in 17 fractions for 3.5 weeks, given as 13 fractions of 3 Gy plus four fractions of 4.5 Gy. The clinical target volume (CTV) included the prostate and the base of seminal vesicles. The CTV-to-PTV (planning target volume) margin was 8-10 mm. Study patients had portal imaging and/or simulation performed on the first fractions and repeated at least weekly. RESULTS: No acute grade 3 or 4 toxicities were observed. The grade 2 GU acute toxicity proportion was significantly lower in the HFRT arm: 19.1% versus 47.7% (chi(2)-test, p = 0.003). The grade 2 GU acute toxicity-free survival was significantly better in the HFRT arm (log-rank test, p = 0.008). The median duration of overall GI acute toxicity was shorter with HFRT: 3 compared to 6 weeks with CFRT (median test, p = 0.017). CONCLUSION: In this first evaluation, the HFRT schedule is feasible and induces acceptable or even lower acute toxicity compared with the toxicities in the CFRT schedule. Extended follow-up is needed to justify this fractionation schedule's safety in the long term.

A randomized trial comparing hypofractionated and conventionally fractionated three-dimensional conformal external-beam radiotherapy for localized prostate adenocarcinoma: a report on the first-year biochemical response.

OBJECTIVE: This paper describes the first-year biochemical (prostate-specific antigen [PSA]) response of 91 irradiated patients enrolled in a single-institution randomized trial comparing hypofractionated (HFRT) and conventionally fractionated (CFRT) external beam radiotherapy. MATERIAL AND METHODS: Forty-four patients in the CFRT treatment arm were irradiated with 74 Gy in 37 fractions (2 Gy per fraction), and 47 in the HFRT arm were treated with 57 Gy, given in 13 fractions of 3 Gy plus 4 fractions of 4.5 Gy. The clinical target volume includes the prostate and a base of seminal vesicles. The proportions of patients who reached PSA nadir (nPSA) lower than or equal to 1.0 ng/mL (nPSA1) and 0.5 ng/mL (nPSA05) were compared. RESULTS: There were 2 non-cancer-related deaths (1 in the CFRT and 1 in the HFRT treatment arms). Biochemical relapse after irradiation was defined in five cases (3 in the CFRT and 2 in the HFRT treatment arms) during a 12-month follow-up. The remaining 84 patients were analyzed. The proportions of patients reaching nPSA1 were 50% and 54.5% in the CFRT and HFRT treatment arms, respectively (chi-square P=0.843). The percentages of patients reaching nPSA05 were 25% and 18.2%, respectively (chi-square P=0.621). The trends toward increasing proportions of biochemical responders (both nPSA1 and nPSA05) during 12 months after radiotherapy were observed, but the difference between trends for treatment arms did not reach a statistical significance. CONCLUSION: The preliminary results presented here demonstrate that HFRT schedule induces biochemical response rates comparable to those in the CFRT schedule during the first-year follow-up.

[A preliminary safety study of hypofractionated radiotherapy for local prostate cancer]. / Neisplitusio priesines liaukos vezio hipofrakcionuoto spindulinio gydymo saugumo tyrimas.

Institute of Oncology of Vilnius University has initiated a randomized clinical trial with the aim to evaluate the effectiveness and toxicity of conventional fractionated (37 fractions, 2.0 Gy per fraction, a total dose of 74 Gy) and hypofractionated (13 fractions, 3.0 Gy per fraction, and 4 fractions at 4.5 Gy per fraction, a total dose of 57 Gy) radiotherapy. The goal of preliminary safety analysis was to compare the acute radiation toxicity in investigated and control groups. A total of 22 patients have been enrolled in this trial; there were 11 patients in each investigated group. Grade IV acute bladder radiation toxicity according to Radiation Therapy Oncology Group (RTOG) toxicity criteria was observed in one control group patient. No grade III acute radiation toxicity was observed. Grade II acute radiation toxicity was observed in 2 patients from hypofractionated radiotherapy group and in 3 from conventional radiotherapy group. Grade I-II acute radiation toxicity was observed in all patients of investigated and control groups. A statistically significant decrease of grade I bladder and rectal toxicity in the hypofractionated arm and grade I bladder toxicity in the conventional arm was observed. Other differences were not significant. A comparatively small number of acute reactions in the patients' group treated with hypofractionated radiotherapy show the safety of the method applied and enable the continuation of this trial.

[The influence of conformal radiotherapy on survival of lung cancer patients]. / Konformalios spindulines terapijos itaka serganciuju plauciu veziu gyvenimo trukmei.

The aim of this study was to analyze survival dependence on 3-D conformal radiotherapy dose applied to non-small cell lung cancer patients treated in Kaunas University of Medicine Hospital from year 1999 to 2001. One hundred fifteen patients with median age 67.3 years were analyzed. There were 101 men and 14 women. Squamous cell carcinoma was the most common type of histology (80.86% patients). Most patients (61.7%) had locally advanced lung cancer (stage III). Radiotherapy doses applied ranged from 30 Gy (3.0 Gy/10 fractions) to 70 Gy (2.0 Gy/35 fractions). After analysis of radiotherapy dose influence on survival statistically significant improvement in median survival with higher doses was found (p=0.0001 Breslow). The group of patients irradiated with higher than 50 Gy dose demonstrated better survival than patients treated with smaller doses. (Log rank p=0.0061, Breslow p=0.0013). There was a correlation between dose and conformity of dose distribution.