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.

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.

[A Case of Effective Chemoradiotherapy Using mFOLFOX6 for Locally Advanced Rectal Cancer].

We report a case of locally advanced rectal cancer, treated effectively with chemotherapy consisting of mFOLFOX6 combined with radiotherapy. A 63-year-old man was admitted to our hospital in March 2012 for diarrhea and anal and perineal pain. Advanced rectal cancer with invasion ofthe right perineum was diagnosed based on computer tomography(CT) findings. Surgery was performed; however, the rectal cancer was unresectable. A sigmoid colostomy was performed, and a central venous port was implanted. In April 2012, the patient was treated with chemotherapy using 3 courses ofmFOLFOX6 and concurrent radiotherapy. Radiotherapy at 2 Gy/day was administered 25 times(total dose, 50 Gy). After chemoradiotherapy, the patient underwent 3 courses ofmFOLFOX6 as an additional therapy. By June 2012, CT showed resolution ofthe tumor in the right perineum and a marked decrease in the size ofthe primary rectal cancer. Because the patient refused surgery, we started treatment with combination chemotherapy using oral S-1 and intravenous CPT-11 in August 2012. After 18 courses, the treatment was changed to oral administration ofS -1 alone, which was continued for 1 year. The patient remained well without recurrence for 54 months since the original diagnosis. Therefore, chemoradiotherapy with mFOLFOX6 is a possible option for the management of advanced rectal cancer.

Long-term outcomes of intraluminal brachytherapy in combination with external beam radiotherapy for superficial esophageal cancer.

BACKGROUND: The aim of this study was to assess the long-term outcomes of combining high-dose-rate intraluminal brachytherapy (IBT) with external beam radiotherapy (EBRT) for superficial esophageal cancer (SEC). METHODS: From 1992 to 2002, 87 patients with T1N0M0 thoracic esophageal cancer received IBT in combination with EBRT. Of these, 44 had mucosal cancer and 43 had submucosal cancer. For patients with tumor invasion within the lamina propria mucosa, IBT alone was performed (n = 27). IBT boost following EBRT was performed for patients with tumor invasion in the muscularis mucosa or deeper (n = 60). No patient received chemotherapy. RESULTS: The median follow-up time was 94 months. For mucosal cancer, the 5-year locoregional control (LRC), cause-specific survival (CSS) and overall survival (OS) rates were 75, 97 and 84%, respectively, and 49, 55 and 31%, respectively, for submucosal cancer. Tumor depth was a significant factor associated with LRC (p = 0.02), CSS (p < 0.001) and OS (p < 0.001) by univariate analysis. Multivariate analysis revealed that tumor depth was the only significant predictor for OS (p = 0.003). Late toxicities of grade 3 or higher in esophagus, pneumonitis, pleural effusion and pericardial effusion were observed in 5, 0, 0 and 1 patients, respectively. Grade ≥3 events of cardiac ischemia and heart failure after radiotherapy were observed in 9 patients, and history of heart disease before radiotherapy was the only significant factor (p = 0.002). CONCLUSION: There was a clear difference in outcomes of IBT combined with EBRT between mucosal and submucosal esophageal cancers. More intensive treatment should be considered for submucosal cancer.

Intra-arterial infusion chemotherapy using cisplatin with radiotherapy for Stage III squamous cell carcinoma of the cervix.

PURPOSE: To examine the effectiveness of concomitant intra-arterial infusion chemotherapy (IAIC) using cisplatin (CDDP) with radiotherapy for Stage III squamous cell carcinoma of the cervix. MATERIALS AND METHODS: We analyzed 29 cases of Stage III squamous cell carcinoma of the uterine cervix treated with radiotherapy and IAIC of CDDP from 1991 to 2006. External-beam therapy was given to the whole pelvis using four opposing parallel fields with an 18-MV linear accelerator unit. A central shield was used after 30-40 Gy with external whole-pelvic irradiation, and the total dose was 50 Gy. High-dose-rate brachytherapy was given with (192)Ir microSelectron. The dose at Point A was 6 Gy per fraction, 2 fractions per week, and the total number of fractions was either 3 or 4. Two or three courses of IAIC were given concomitantly with CDDP 120 mg or carboplatin 300 mg. RESULTS: We confirmed excellent medicine distribution directly by using computed tomographic angiography. The 5-year overall survival rate for Stage III patients was 62%, the cause-specific survival rate was 70%, and the local relapse-free survival rate was 89%. Local recurrence, distant metastasis, and occurrences of both were 7%, 38%, and 3%, respectively. The incidence of severe acute hematologic adverse reactions (Grade > or =3) was 27% for all patients; however, all recovered without interruption of radiotherapy. Severe nonhematologic effects (Grade > or =3) were 3%, including nausea and ileus. Only 1 patient's radiotherapy was interrupted for a period of 1 week because of ileus. Severe late complication rates (Grade > or =3) for the bladder, rectum, and intestine were 3%, 3%, and 10%, respectively. CONCLUSION: A combination of IAIC and systemic chemotherapy should be considered to improve the prognosis of patients with Stage III squamous cell carcinoma of the cervix.

[Concurrent chemoradiation experience of the local relapse of rectal cancer patients].

We have reported the concurrent chemoradiation experience of local relapse of rectal cancer patients. From October 2004 to January 2007 we have treated consecutive 10 patients with radiation and the concurrent chemotherapy by CPT-11+S-1. Of 10 lesions, 5(50%)had a complete response, 2(20%)a partial response, 3(30%)a stable disease, yielding an overall response rate of 70%. Three year survival and relapse free survival was 64% and 22 months, respectively. Four patients live without cancers, 3 patients died with cancers and 2 patients live with cancers. Three patients had acute complication(more than Grade 2)including 3 appetite losses. The concurrent chemoradiation is feasible for out-patients and seems to offer good results for the local relapse of rectal cancer patients.

Treatment results of adjuvant radiotherapy and salvage radiotherapy after radical prostatectomy for prostate cancer.

BACKGROUND: The indications for and the efficacy of radiation therapy after radical operation for patients with prostate cancer are not clear. We analyzed the treatment results of adjuvant radiotherapy and salvage radiotherapy after radical prostatectomy. METHODS: Between September 1997 and November 2004, 57 patients received adjuvant radiotherapy or salvage radiotherapy after radical prostatectomy. Fifteen patients received radiation therapy because of positive margins and/or extracapsular invasion in surgical specimens (adjuvant group). Forty-two patients received radiation therapy because of rising prostate-specific antigen (PSA) during follow-up (salvage group). Radiation therapy was delivered to the fossa of the prostate +/- seminal vesicles by a three-dimensional (3-D) conformal technique to a total dose of 60-66 Gy (median, 60 Gy). Biochemical control was defined as the maintenance of a PSA level of less than 0.2 ng/ml. RESULTS: The median follow-up period after radiation therapy was 33 months (range, 12-98 months). Three-year biochemical control rates were 87% for the adjuvant group and 61% for the salvage group. For patients in the salvage group treated without hormone therapy, the preradiation PSA value was the most significant factor for the biochemical control rate. The 3-year biochemical control rate was 93% in patients whose preradiation PSA was 0.5 ng/ml or less and 29% in patients whose preradiation PSA was more than 0.5 ng/ml. No severe adverse effects (equal to or more than grade 3) were seen in treated patients. CONCLUSION: Radiation therapy after radical prostatectomy seemed to be effective for adjuvant therapy and for salvage therapy in patients with a preradiation PSA of 0.5 ng/ml or less. Also, radiation to the fossa of the prostate +/- seminal vesicles, to a total dose of 60-66 Gy, using a three-dimensional (3-D) conformal technique, seemed to be safe.

CT appearance of radiation injury of the lung and clinical symptoms after stereotactic body radiation therapy (SBRT) for lung cancers: are patients with pulmonary emphysema also candidates for SBRT for lung cancers?

PURPOSE: The purpose of this study was to analyze the computed tomographic (CT) appearance of radiation injury to the lung and clinical symptoms after stereotactic body radiation therapy (SBRT) and evaluate the difference by the presence of pulmonary emphysema (PE) for small lung cancers. METHODS AND MATERIALS: In this analysis, 45 patients with 52 primary or metastatic lung cancers were enrolled. We evaluated the CT appearance of acute radiation pneumonitis (within 6 months) and radiation fibrosis (after 6 months) after SBRT. Clinical symptoms were evaluated by Common Terminology Criteria for Adverse Events, version 3.0. We also evaluated the relationship between CT appearance, clinical symptoms, and PE. RESULTS: CT appearance of acute radiation pneumonitis was classified as follows: (1) diffuse consolidation, 38.5%; (2) patchy consolidation and ground-glass opacities (GGO), 15.4%; (3) diffuse GGO, 11.5%; (4) patchy GGO, 2.0%; (5) no evidence of increasing density, 32.6%. CT appearance of radiation fibrosis was classified as follows: (1) modified conventional pattern, 61.5%; (2) mass-like pattern, 17.3%; (3) scar-like pattern, 21.2%. Patients who were diagnosed with more than Grade 2 pneumonitis showed significantly less no evidence of increased density pattern and scar-like pattern than any other pattern (p=0.0314, 0.0297, respectively). Significantly, most of these patients with no evidence of increased density pattern and scar-like pattern had PE (p=0.00038, 0.00044, respectively). CONCLUSION: Computed tomographic appearance after SBRT was classified into five patterns of acute radiation pneumonitis and three patterns of radiation fibrosis. Our results suggest that SBRT can be also safely performed even in patients with PE.

[Concurrent chemoradiation using daily low-dose CDDP and UFT-E for postoperative recurrent esophageal cancers].

We reported concurrent chemoradiation for postoperative recurrent esophageal cancer patients with lymph node metastases and a pulmonary metastasis. From October 2001 to January 2004, we treated 6 consecutive patients with radiation and concurrent chemotherapy using daily low-doses of CDDP and UFT-E. Of the 6 patients, 4 (67%) had a complete response and 2 (33%) a partial response, yielding an overall response rate of 100% (6/6). Five patients are now alive without cancers, and 1 patient died with cancer. Concurrent chemoradiation using daily low-doses of CDDP and UFT-E is feasible and seems to offer good results for recurrent esophageal cancer patients.

[Concurrent chemoradiation experience of recurrent gastric cancers resistant to TS-1].

We report our experience with concurrent chemoradiation for recurrent gastric cancers resistant to TS-1. From April 2000 to March 2003, we treated 10 consecutive patients with radiation and the concurrent single chemotherapy agent of TS-1 or CPT-11. Of the 10 patients, 3 (30%) had a complete response, 4 (40%) a partial response, and 3 (30%) stable disease, yielding an overall response rate of 70% (7/10). Three patients are alive and cancer-free, 5 patients died with cancers, and 2 patients are living with cancers as outpatients. The clinical benefit response was 90% (9/10). No patient has had either acute or late complication. Concurrent chemoradiation is feasible and seems to offer good results for recurrent gastric cancers resistant to TS-1.