The influence of Gleason score ≤ 6 histology on the outcome of high-risk localized prostate cancer after modern radiotherapy.

We aimed to retrospectively review outcomes in patients with high-risk prostate cancer and a Gleason score ≤ 6 following modern radiotherapy. We analyzed the outcomes of 1374 patients who had undergone modern radiotherapy, comprising a high-risk low grade [HRLG] group (Gleason score ≤ 6; n = 94) and a high-risk high grade [HRHG] group (Gleason score ≥ 7, n = 1125). We included 955 patients who received brachytherapy with or without external beam radio-therapy (EBRT) and 264 who received modern EBRT (intensity-modulated radiotherapy [IMRT] or stereotactic body radiotherapy [SBRT]). At a median follow-up of 60 (2-177) months, actuarial 5-year biochemical failure-free survival rates were 97.8 and 91.8% (p = 0.017), respectively. The frequency of clinical failure in the HRLG group was less than that in the HRHG group (0% vs 5.4%, p = 0.012). The HRLG group had a better 5-year distant metastasis-free survival than the HRHG group (100% vs 96.0%, p = 0.035). As the HRLG group exhibited no clinical failure and better outcomes than the HRHG group, the HRLG group might potentially be classified as a lower-risk group.

Ultra-High Prostate-Specific Antigen Level: A Potential Very-High-Risk Factor for Localized High-Risk Prostate Cancer.

To examine the impact of ultra-high iPSA levels of >50 ng/mL (uhPSA) after modern radiotherapy, we compared outcomes of 214 patients with uhPSA levels to 1161 other high-risk patients. Radiotherapy included brachytherapy ± external beam radiotherapy (EBRT) and EBRT alone (intensity-modulated radiotherapy or stereotactic body radiotherapy). The biochemical disease-free survival rate (bDFS), the distant metastasis-free survival rate (DMFS), local control, and pelvic lymph node control were analyzed. Patients with uhPSA levels had an inferior bDFS (84.8% at 5 years) and DMFS (93.9% at 5 years) compared to other high-risk patients (92.7% and 97.2%, both p < 0.001). The uhPSA group showed more distant metastases than the non-uhPSA group; however, the frequencies of local failure and pelvic lymph node recurrence were similar. The uhPSA group demonstrated hazard ratios (HRs) of 2.74 for bDFS and 2.71 for DMFS, similar to those of T3b-4 (HR 2.805 and 2.678 for bDFS and DMFS) and GS 9-10 (HR 2.280 and 2.743 for bDFS and DMFS). An uhPSA level could be a candidate for a single VHR factor to identify high-risk patients who require intensified treatment.

Role of Brachytherapy Boost in Clinically Localized Intermediate and High-Risk Prostate Cancer: Lack of Benefit in Patients with Very High-Risk Factors T3b-4 and/or Gleason 9-10.

This study examined the role of brachytherapy boost (BT-boost) and external beam radiotherapy (EBRT) in intermediate- to high-risk prostate cancer, especially in patients with very high-risk factors (VHR: T3b-4 or Gleason score 9-10) as patients with double very high-risk factors (VHR-2: T3b-4 and Gleason score 9-10) previously showed worst prognosis in localized prostate cancer. We retrospectively reviewed multi-institutional data of 1961 patients that were administered radiotherapy (1091 BT-boost and 872 EBRT: 593 conventional-dose RT (Conv RT: equivalent to doses of 2 Gy per fraction = EQD2 ≤ 72 Gy) and 216 dose-escalating RT (DeRT = EQD2 ≥ 74 Gy). We found that BT-boost improved PSA control and provided an equivalent overall survival rate in the intermediate- and high-risk groups, except for patients within the VHR factor group. In the VHR-1 group (single VHR), BT-boost showed a superior biochemical control rate to the Conv RT group but not to the DeRT group. In the VHR-2 group, BT-boost did not improve outcomes of either Conv RT or DeRT groups. In conclusion, BT-boost showed no benefit to modern DeRT in the patients with VHR; therefore, they are not good candidates for BT-boost to improve outcome and may be amenable to clinical trials using multimodal intensified systemic treatments.

Conventional dose versus dose escalated radiotherapy including high-dose-rate brachytherapy boost for patients with Gleason score 9-10 clinical localized prostate cancer.

As several recent researches focus on the importance of Gleason 9-10, we examine the role of radiotherapy dose escalation in those patients. We analyzed 476 patients with Gleason score 9-10 prostate cancer treated with radiotherapy. Of them, 127 patients were treated with conventional-dose external beam radiotherapy (Conv RT) and 349 patients were treated with high-dose radiotherapy (HDRT; 249 patients received high-dose-rate brachytherapy boost + external beam radiotherapy [HDR boost] and 100 patients received intensity-modulated radiotherapy [IMRT]). We compared these treatment groups using multi-institutional retrospective data. The patients had a median follow-up period of 66.3 months. HDRT showed superior biochemical disease-free survival (bDFS) rate (85.2%; HDR boost 84.7% and IMRT 86.6%) to Conv RT (71.1%, p < 0.0001) at 5 years, with a hazard ratio of 0.448. There were borderline difference in prostate cancer-specific mortality (PCSM; 4.3% and 2.75%, p = 0.0581), and distant metastasis-free survival (DMFS; 94.4% and 89.6%, p = 0.0916) rates at 5-years between Conv RT and HDRT group. Dose escalated radiotherapy showed better bDFS, borderline improvement in PCSM, and equivocal outcome in DMFS in with clinically localized Gleason 9-10 prostate cancer.

Novel Prognostic Index of High-Risk Prostate Cancer Using Simple Summation of Very High-Risk Factors.

This study aimed to examine the role of very high-risk (VHR) factors (T3b-4 and Gleason score 9-10) for prognosis of clinically localized high-risk prostate cancer. We reviewed multi-institutional retrospective data of 1413 patients treated with radiotherapy (558 patients treated with external beam radiotherapy (EBRT) and 855 patients treated with brachytherapy (BT) ± EBRT. We introduced an index by simple summation of the number of VHR factors-VHR-0, VHR-1, and VHR-2. With median follow-up of 69.6 months, the 5-year biochemical disease free survival rate (bDFS), prostate cancer-specific mortality (PCSM), and distant metastasis-free survival (DMSF) rates were 59.4%, 7.65%, and 83.2% for the VHR-2 group, respectively; 86.7%, 1.50%, and 95.4% for the VHR-1 group, respectively; and 93.1%, 0.12%, and 98.2% for the VHR-0 group, respectively. The VHR-2 group had significantly worse bDFS, PCSM, and DMSF than the VHR-0 (hazard ratios: 4.55, 9.607, and 7.904, respectively) and VHR-1 (hazard ratios: 1.723, 2.391, and 1.491, respectively) groups. The VHR-2 group could be identified as a super high-risk group compared with other groups, and could be a good candidate for clinical trials using multimodal intensified treatments. Simple summation of the number of VHR factors is an easy and useful predictive index for bDFS, PCSM, and DMSF.

Radiotherapy for Clinically Localized T3b or T4 Very-High-Risk Prostate Cancer-Role of Dose Escalation Using High-Dose-Rate Brachytherapy Boost or High Dose Intensity Modulated Radiotherapy.

To examine the efficacy of dose escalating radiotherapy into patients with cT3b or T4 localized prostate cancer, we compared Group A (86 conventional dose external beam radiotherapy: EBRT group, treated with 70-72 Gy) and group B (39 high dose EBRT group (HDEBRT group, 74-80 Gy) and 124 high-dose-rate brachytherapy (HDR) + EBRT (HDR boost)) using multi-institutional retrospective data. The actuarial 5-year biochemical disease-free survival (bDFS) rate, prostate cancer specific survival rate (PSS), and overall survival rate (OS) were 75.8%, 96.8%, and 93.5%. Group B showed superior 5-year bDFS rate (81.2%) as compared to the group A (66.5%) (p < 0.0001) with a hazard ratio of 0.397. Equivocal 5-year PSS (98.3% and 94.8% in group B and group A) and OS (both 93.7%) were found between those groups. Accumulated late grade ≥ 2 toxicities in gastrointestinal and genitourinary tracts were similar among those three groups. Therefore, both HDEBRT and HDR boost could be good options for improving the bDFS rate in cT3-T4 localized prostate cancer without affecting PSS and OS.

Ultrahypofractionated Radiotherapy versus Conventional to Moderate Hypofractionated Radiotherapy for Clinically Localized Prostate Cancer.

The purpose of this study was to compare the toxicity (first endpoint) and efficacy (second endpoint) of ultrahypofractionated radiotherapy (UHF) and dose-escalated conventional to moderate hypofractionated radiotherapy (DeRT) for clinically localized prostate cancer. We compared 253 patients treated with UHF and 499 patients treated with DeRT using multi-institutional retrospective data. To analyze toxicity, we divided UHF into High-dose UHF (H-UHF; equivalent doses of 2 Gy per fraction: EQD2 > 100 Gy1.5) and low-dose UHF (L-UHF; EQD2 ≤ 100 Gy1.5). In toxicity, H-UHF elevated for 3 years accumulated late gastrointestinal and genitourinary toxicity grade ≥ 2 (11.1% and 9.3%) more than L-UHF (3% and 1.2%) and DeRT (3.1% and 4.8%, p = 0.00126 and p = 0.00549). With median follow-up periods of 32.0 and 61.7 months, the actuarial 3-year biochemical failure-free survival rates were 100% (100% and 100% in the L-UHF and H-UHF) and 96.3% in the low-risk group, 96.5% (97.1% and 95.6%) and 94.9% in the intermediate-risk group, and 93.7% (100% and 94.6%) and 91.7% in the high-risk group in the UHF and DeRT groups, respectively. UHF showed equivocal efficacy, although not conclusive but suggestive due to a short follow-up period of UHF. L-UHF using EQD2 ≤ 100 Gy1.5 is a feasible UHF schedule with a good balance between toxicity and efficacy.

Radiotherapy for elder patients aged ≥80 with clinically localized prostate cancer - Brachytherapy enhanced late GU toxicity especially in elderly.

BACKGROUND AND PURPOSE: Elongation of life expectancy had led to marked increase in number of elderly patients with localized prostate cancer. However, the standard treatment for such patients is not well determined because of a high prevalence of comorbidities and slow growth of prostate cancer. The aim of this study is to examine the feasibility of radiotherapy for elderly patients aged ≥80 years. MATERIALS AND METHODS: We compared 96 patients aged ≥80 years and 2333 younger patients (aged 60-79 years) using multi-institutional data included cT1-T4N0M0 prostate cancer treated with 902 external beam radiotherapy (EBRT) and 1527 brachytherapy (BT). RESULTS: The 5-year biochemical failure-free survival rate was similar between elderly ≥80 years and younger control (91.3% vs. 85.9%, p = 0.6171) (100%, 92.9%, 82.4% and 96.3%, 93.7%, 89% for low, intermediate and high risk group), and for the prostate cancer-specific survival rate (100% and 99.3%, p = 0.6171). The accumulated incidence of late gastrointestinal (GI) at 5 years was also similar between elderly and younger patients (3.5% vs. 2.5%, p = 0.6857). Brachytherapy improved biochemical control rate and reduced GI toxicity compared with EBRT, however, enhanced late genitourinary (GU) toxicity, especially in elderly patients. Elderly received brachytherapy showed highest rate of late GU toxicity grade ≥2 of 22.1% than the younger counterparts of 12.7% at 5 years, whereas younger patients treated with EBRT had 2.4% and elderly EBRT had 2.7% (p < 0.0001). CONCLUSION: Elderly patients aged ≥80 years showed equivalent biochemical control, prostate cancer-related survival, and gastrointestinal toxicity profiles to younger patients. Meticulous care should be required for brachytherapy enhanced late GU toxicity, especially in elderly patients aged ≥80 years.

Effect of Androgen Deprivation Therapy on Other-Cause of Mortality in Elderly Patients with Clinically Localized Prostate Cancer Treated with Modern Radiotherapy: Is There a Negative Impact?

The influence of androgen deprivation therapy (ADT) on other-cause of mortality (OCM) was investigated in patients with localized prostate cancer treated with modern high-dose radiotherapy. A retrospective review was conducted on 1125 patients with localized prostate cancer treated with high-dose radiotherapy, including image-guided, intensity-modulated radiotherapy or brachytherapy with a median follow-up of 80.7 months. Overall survival rate was no different between ADT (+) and ADT (-) group in high-, intermediate-, and low-risk groups. OCM was found in 71 patients, consisting of 4% (10/258) in the ADT (-) group and 7% (61/858) in the ADT (+) group (p = 0.0422). The 10-year OCM-free survival rate (OCMFS), if divided by the duration of ADT (ADT naïve (ADT (-)), ADT <2-year, and ADT ≥2-year groups), showed statistical significance, and was 90.7%, 88.2%, and 78.6% (p = 0.0039) for the ADT (-), ADT <2-year, and ADT ≥2-year groups, respectively. In patients aged ≥75 years, 10-year OCMFS for ADT (-), ADT <2-, and ADT ≥2-year groups was 93.5% (at 115.6 months), 85.6%, and 60.7% (p = 0.0189), respectively, whereas it was 90.7%, 89.9%, and 89.0% (p = 0.4716), respectively, in their younger counterparts. In localized prostate cancer patients, treatment with longer ADT for ≥2 years potentially increases the risk of OCM, especially in patients aged ≥75 years.

Radiothrerapy for Elderly Patients Aged ≥75 Years with Clinically Localized Prostate Cancer-Is There a Role of Brachytherapy?

We compared radiotherapy outcomes between 241 elderly patients aged ≥75 years and 867 younger controls (age <75 years) with clinically localized prostate cancer. The elderly group showed an equivalent actuarial seven-year biochemical failure-free survival rate (7y-bNED) (94.9%) to the younger control group (96.4%, p = 0.593). The incidence of late genitourinary (GU) and gastrointestinal (GI) toxicities grade ≥2 was also similar between the elderly and younger cohorts, while no grade ≥4 adverse events occurred. We also examined the role of brachytherapy (BT) in the elderly group, in comparison with image-guided intensity-modulated radiotherapy (IG-IMRT). BT showed superior 7y-bNED (94.1%) than IG-IMRT (84.6%, p = 0.0183) in elderly patients, which was 100% (100% for BT and 100% for IG-IMRT, p > 0.999) for the low-risk group, 94.6% (92.8% and 100%, p = 0.203) for the intermediate-risk group, and 80.5% (91.2% and 73.6%, p = 0.0195) for the high-risk group. BT showed higher GU toxicity and equivalent GI toxicity to IG-IMRT. In conclusion, elderly patients showed bNED and toxicity that were equivalent to those observed in younger controls, and BT is a plausible option also for healthy elderly with potential to improve bNED, with higher but acceptable GU toxicity.

Author Correction: Comparison of Image-Guided Intensity-Modulated Radiotherapy and Low-dose Rate Brachytherapy with or without External Beam Radiotherapy in Patients with Localized Prostate Cancer.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

High-Dose-Rate Brachytherapy Monotherapy versus Image-Guided Intensity-Modulated Radiotherapy with Helical Tomotherapy for Patients with Localized Prostate Cancer.

The aim of this paper is to compare outcomes between high-dose-rate interstitial brachytherapy (HDR-BT) monotherapy and image-guided intensity-modulated radiotherapy (IG-IMRT) for localized prostate cancer. We examined 353 HDR-BT and 270 IG-IMRT patients. To reduce background selection bias, we used the method of inverse probability treatment weighting (IPTW) with propensity scores. The actuarial five-year biochemical failure-free survival rates were 92.9% and 96.7% (p = 0.1847; p = 0.077 in IPTW) for HDR-BT and IG-IMRT, respectively; they were 100% and 95.8% (p = 0.286) for the low-risk group, 95.6% and 92% (p = 0.42) for the intermediate-risk group, 90.4% and 84.9% (p = 0.1059; p = 0.04 in IPTW) for the high-risk group, and 87.1% and 89.2% (p = 0.3816) for the very-high-risk group. In the assessment of accumulated incidences of grade ≥ 2 toxicity (Common Terminology Criteria for Adverse Events version 4.0) at five years, HDR-BT monotherapy showed higher genitourinary toxicity (11.9%) than IG-IMRT (3.3%) (p < 0.0001). The gastrointestinal toxicity was equivalent for HDR-BT (2.3%) and IG-IMRT (5.5%) (p = 0.063). No Grade 4 or 5 toxicity was detected in either modality. HDR-BT showed higher genitourinary toxicity than IG-IMRT. HDR-BT and IG-IMRT showed equivalent outcomes in low-, intermediate-, and very-high-risk groups. For high-risk patients, HDR-BT showed potential to improve prostate-specific antigen (PSA) control rate compared to IG-IMRT.

Comparison of Image-Guided Intensity-Modulated Radiotherapy and Low-dose Rate Brachytherapy with or without External Beam Radiotherapy in Patients with Localized Prostate Cancer.

To compare the outcome of low-dose rate brachytherapy (LDR-BT) and image-guided intensity-modulated radiotherapy (IG-IMRT) for localized prostate cancer, we examined 488 LDR-BT and 269 IG-IMRT patients. IG-IMRT treated older and advanced disease with more hormonal therapy than LDR-BT, which excluded T3b-T4 tumor and initial PSA > 50 ng/ml. The actuarial five-year biochemical failure-free survival rate was 88.7% and 96.7% (p = 0.0003) in IG-IMRT and LDR-BT, respectively; it was 88.2% (85.1% for IG-IMRT and 94.9% for LDR-BT, p = 0.0578) for the high-risk group, 95.2% (91.6% and 97.0%, p = 0.3361) for the intermediate IG-IMRT and 96.8% (95.7% and 97%, p = 0.8625) for the low-risk group. Inverse probability of treatment weighting (IPTW) involving propensity scores was used to reduce background selection bias. IPTW showed a statistically significant difference between LDR-BT and IG-IMRT in high risk (p = 0.0009) and high risk excluding T3-4/initial PSA > 50 ng/ml group (p = 0.0073). IG-IMRT showed more gastrointestinal toxicity (p = 0.0023) and less genitourinary toxicity (p < 0.0001) than LDR-BT. LDR-BT and IG-IMRT showed equivocal outcome in low- and intermediate-risk groups. For selected high-risk patients, LDR-BT showed more potential to improve PSA control rate than IG-IMRT.

Long-term Outcomes of a Dose-reduction Trial to Decrease Late Gastrointestinal Toxicity in Patients with Prostate Cancer Receiving Soft Tissue-matched Image-guided Intensity-modulated Radiotherapy.

BACKGROUND/AIM: We experienced an unexpected high incidence of gastrointestinal (GI) toxicity in patients undergoing image-guided intensity-modulated radiotherapy (IG-IMRT) using helical tomotherapy in our initial 2.2 Gy/fraction schedule for prostate cancer; hence, a dose-reduction trial from 2.2 Gy to 2 Gy/fraction was conducted using modified planning target volume (PTV) contouring. PATIENTS AND METHODS: We compared 130 patients treated using 2.2 Gy/fraction (Group A) and 144 treated using the 2 Gy/fraction (Group B) with modified PTV (excluding rectal volume) with a median follow-up period of 62 months. Prescribed dose was 72.6-74.8 Gy in 33-34 fractions (Group A) and 72-74 Gy in 36-37 fractions (Group B). RESULTS: Patients in Group B had a reduced rectal and bladder V10-V70 and were irradiated at the maximal dose. Their cumulative incidence of grade ≤2 GI toxicity at 5 years improved from 10.1% [95% confidence interval (CI), 4.9-15.3%] to 1.4% (0-3.3%). Grade 2≤ urinary toxicity also decreased from 5.5% (1.5-9.4%) in Group A to 1.4% (0-3.3%, p=0.0167) in Group B. The biochemical failure-free 5-year survival rate was 89.1% (95%CI=83.6-95.4%) and 87.5% (82.0-92.9%, p=0.75) in groups A and B, respectively. CONCLUSION: The reduced dose fraction schedule decreased the incidence of late GI toxicity without compromising prostate-specific antigen control. Careful target volume definition and fraction size are important even for IG-IMRT.

Interfractional Rectal Displacement Requiring Repeated Precaution Did Not Correlate to Biochemical Control and Rectal Toxicity in Patients with Prostate Cancer Treated with Image-guided Intensity-modulated Radiation Therapy.

AIM: To investigate the correlation between frequency of action level of interfractional rectal displacement requiring repeated precaution in patients with prostate cancer and late toxicity from image-guided intensity-modulated radiation therapy (IG-IMRT) using helical tomotherapy. PATIENTS AND METHODS: We examined 264 patients who underwent IG-IMRT during 2007-2011. Megavoltage computed tomographic (MVCT) images were acquired before radiation therapy and was examined with soft-tissue matching by comparing treatment planning images within 9,345 fractions. Displacement of the anterior rectal region larger than 5 mm, requiring repeated precaution, was defined as the level of rectal displacement requiring action (ARD). RESULTS: ARD was identified in 815 (7.7%) out of 9,345 fractions and at least once in 82% (216/264) of patients. The highest incidence of ARD (11%) was found during the initial week of treatment (first five and next five fractions), after which the incidence decreased to 6% (p<0.0001). Patients with lean body (lower body mass index (BMI) tended to have a higher incidence of ARD. We identified 16 (6%) cases of gastrointestinal toxicity and 12 (4.5%) genitourinary toxicities as a late adverse reaction (3 months or later after IG-IMRT). There was no correlation between ARD and late toxicity. Prostate-specific antigen (PSA) control was also similar (p=0.12) between those with ARD (96% at 5 year) and those without ARD (88%). CONCLUSION: ARD occurred predominantly in lean patients, during the initial week of treatment and became less likely over time. ARD was not correlated to late toxicity and PSA control, therefore, IG-IMRT technique was able to adequately control error due to interfractional prostate and rectal motion.

Long-term Tumor Control and Late Toxicity in Patients with Prostate Cancer Receiving Hypofractionated (2.2 Gy) Soft-tissue-matched Image-guided Intensity-modulated Radiotherapy.

AIM: We report the long-term tumor control and toxicity outcomes of patients undergoing hypofractionated (2.2 Gy) image-guided intensity-modulated radiotherapy (IG-IMRT) using tomotherapy for clinically localized prostate cancer. PATIENTS AND METHODS: We examined the cases of 138 consecutive patients with stage T1-T3 prostate cancer that were treated with IG-IMRT from June 2007 to July 2009. The median follow-up time was 79 months (range=31-96 months). The planning target volume received a dose of 72.6-74.8 Gy in 33-34 fractions (2.2 Gy/fraction). Megavoltage computed tomographic (CT) scans were performed before each treatment and corrected to the registered positions on the planning CT scans using prostate soft-tissue matching. RESULTS: The 5-year biochemical and clinical relapse-free survival rates were 95% for the low-risk group, 92% for the intermediate-risk group, and 77% for the high-risk group. The 5-year incidence rates of grade 2 and 3 late gastrointestinal toxicities were 6.3% and 3.1%, respectively, and those of grade 2 and 3 late genitourinary toxicities were 7.9% and 0%, respectively. Multivariate analysis indicated that T-stage is a prognostic factor for biochemical relapse-free survival rates. CONCLUSION: This report involved the longest followed-up cohort of patients to have received hypofractionated (2.2 Gy) soft tissue-matched IG-IMRT using tomotherapy. The findings of this study indicate that hypofractionated IMRT is well tolerated and is associated with good long-term tumor-control outcomes in patients with localized prostate cancer.

Clinical outcome of patients treated with re-irradiation for spine or pelvic bone metastasis: A multi-institutional analysis of 98 patients.

The present study aimed to describe the clinical results of re-irradiation (Re-RT) for spine or pelvic bone metastasis at the same initial irradiated area. Between April 2010 and March 2014, cases involving 98 patients with spine or pelvic bone metastasis who had undergone Re-RT at five institutions were reviewed. The clinical outcomes following Re-RT were evaluated, including overall survival (OS) and severe adverse events. The median time interval from initial radiation therapy (RT) to Re-RT was 439 days (range, 23-4,993 days), and the median duration of patient follow-up was 256 days (range, 11-2,284 days). The median biological effective dose for the Re-RT was 150 Gy2 (range, 17-240 Gy2; α/ß = 2). Severe late adverse events occurred in two patients who underwent three-dimensional conformal radiotherapy for lumbar spine or pelvic bone metastases, which may be associated with tumor progression. The median survival time following Re-RT was 255 days, and the actuarial OS rate at 1 year was 36%. The interval between initial RT and Re-RT, and their performance statuses (PS) were significant independent prognostic factors for OS rates in multivariate analysis. Re-RT for spine or pelvic bone metastases is a relatively acceptable option with low risk of anticipated severe adverse events, particularly for patients with good PS following a long disease-free interval.

Phase II study on hepatic arterial infusion chemotherapy using percutaneous catheter placement techniques for liver metastases from colorectal cancer (JFMC28 study).

AIM: This prospective multicenter study aimed to evaluate the efficacy and adverse events of hepatic arterial infusion chemotherapy (HAIC) using percutaneous catheter placement techniques for liver metastases from colorectal cancer (CRC). METHODS: We administered 5-fluorouracil at 1000 mg/m2 over 5 h via hepatic arterial infusion on a weekly schedule. The primary endpoint was the overall response rate (RR). The secondary endpoints were the overall survival (OS), progression-free survival (PFS) and toxicities. RESULTS: Between February 2000 and March 2002, seventy-seven eligible patients were enrolled in this study. After a median of 26 treatment cycles, 4 patients achieved a complete response, 29 achieved a partial response, 28 had stable disease, 15 had progressive disease and the status of one patient was unknown. The overall RR was 42.9% and the disease control rate (DCR) was 79.2%. The median PFS and OS times were 203 and 560 days, respectively. The most common grade 3 or 4 hematological and non-hematological toxicities were total bilirubin level elevation (10.4%) and gamma-glutamyl transferase level elevation (10.4%). With regard to the relationship between the background factors and treatment outcomes, the DCR, RR, PFS and OS were different between patients with and without extrahepatic lesions (DCR: 86.5% vs 64%, RR: 46.2% vs 36.0%, PFS: 233 days vs 99 days, OS: 587 days vs 558 days). CONCLUSION: The primary endpoint of this study was not met. HAIC using percutaneous catheter placement techniques did not improve the RR for liver metastasis from CRC.

Frequency and predisposing factors for interfractional rectal displacement requiring repeated precaution in prostate cancer patients treated with image-guided intensity-modulated radiation therapy.

AIM: To investigate the frequency and characteristics of interfractional rectal displacement in patients with prostate cancer treated with image-guided intensity-modulated radiation therapy (IG-IMRT) using helical tomotherapy. PATIENTS AND METHODS: Data for a total of 256 patients were analyzed. Megavoltage computed tomography (MVCT) images were acquired before radiation therapy and interfractional rectal displacement was assessed with soft-tissue matching by comparing treatment planning images within 9,445 fractions. Anterior rectal region displacement larger than 5 mm, requiring repeated precaution, was defined as the action level of rectal displacement (ARD). RESULTS: ARD was identified in 676 (7.2%) out of 9,445 fractions and at least once in 75% (190/256) of patients. Univariate analysis identified three predisposing factors for ARD: body mass index (BMI), rectal volume and prostate volume. Multivariate logistic regression analysis revealed that lower BMI and large rectal volume were statistically significant predictors of ARD. The highest incidence of ARD (13.6% and 9.1%) was found during the initial two weeks of treatment (first five and next five fractions), after which the incidence decreased to 5.96% (p<0.0001). CONCLUSION: ARD was identified in 7.9% of fractions and in 74.8% of patients and was most likely to occur in patients with a low BMI and/or large rectal volume. ARD occurred predominantly during the initial two weeks of treatment and became less likely over time.

Analysis of intrafractional organ motion by megavoltage computed tomography in patients with lung cancer treated with image-guided stereotactic body radiotherapy using helical tomotherapy.

AIM: To analyze intrafractional organ motion in patients with lung cancer treated with image-guided stereotactic body radiotherapy using helical tomotherapy (SBRT-HT). PATIENTS AND METHODS: Data from 25 patients with lung cancer who received 50 Gy/5 fractions of SBRT-HT were analyzed. Slow-scan megavoltage computed tomography (MVCT) images were acquired before (pre-MVCT) and after (post-MVCT) each fraction. We analyzed the imaging quality of the 124 post-MVCT images to identify tumor contours using low-density settings. Next we examined tumor contour deviations from the planning target volume (PTV) in post-MVCT images for intrafractional tumor displacement. RESULTS: Image quality was determined as good in 111/124 images from 22 patients (92%). None of the upper lung tumor images were of poor quality (74 images in 15 patients), whereas lower lung tumors yielded 14 poor-quality images out of the 50 images (3/10 patients). The difference in image quality between upper and lower lung tumors was statistically significant (p<0.01), especially when accompanied by interstitial lung shadows. Deviations in tumor position in post-MVCT images were analyzed in 110 images from 23 patients and revealed 99 images (90%) with tumor contours confined to PTV. In upper lung tumors, 4/74 images in 15 patients (5.4%) showed tumor contour deviations outside PTV. Lower lung tumors showed a higher rate of deviation with 7/36 images in 8 patients (19.4%) showing tumor contour deviations outside PTV (p<0.05). The maximum deviation was 1 mm for upper lung tumors and 2 mm for lower lung tumors. CONCLUSION: Upper lung tumors are good candidates for MVCT image-guided SBRT-HT. However, lower lung tumors, especially those adjacent to the diaphragm or pleura, can be difficult to assess, warranting precise dose delivery by MVCT image-guided SBRT-HT.