Adjuvant radiotherapy after prostatectomy for prostate cancer in Japan: a multi-institutional survey study of the JROSG

In Japan, the use of adjuvant radiotherapy after prostatectomy for prostate cancer has not increased compared with the use of salvage radiotherapy. We retrospectively evaluated the outcome of adjuvant radiotherapy together with prognostic factors of outcome in Japan. Between 2005 and 2007, a total of 87 patients were referred for adjuvant radiotherapy in 23 institutions [median age: 64 years (54–77 years), median initial prostate-specific antigen: 11.0 ng/ml (2.9–284 ng/ml), Gleason score (GS): 6, 7, 8, 9, 10 = 13.8, 35.6, 23.0, 27.6, 0%, respectively]. Rates of positive marginal status, seminal vesicle invasion (SVI) and extra-prostatic extension (EPE) were 74%, 26% and 64%, respectively. Median post-operative PSA nadir: 0.167 ng/ml (0–2.51 ng/ml). Median time from surgery to radiotherapy was 3 months (1–6 months). A total dose of ≥60 Gy and <65 Gy was administered to 69% of patients. The median follow-up time was 62 months. The 3- and 5-year biochemical relapse-free survival (bRFS) rates for all patients were 66.5% and 57.1%, respectively. The GS and marginal status (P = 0.019), GS and SVI (P = 0.001), marginal status and EPE (P = 0.017), type of hormonal therapy and total dose (P = 0.026) were significantly related. The 5-year bRFS rate was significantly higher in SVI-negative patients than SVI-positive patients (P = 0.001), and significantly higher in patients with post-operative PSA nadir ≤0.2 than in patients with post-operative PSA nadir >0.2 (P = 0.02), and tended to be more favorable after radiotherapy ≤3 months from surgery than >3 months from surgery (P = 0.069). Multivariate analysis identified SVI and post-operative PSA nadir as independent prognostic factors for bRFS (P = 0.001 and 0.018, respectively).     

Dosimetric evaluation of ovaries and pelvic bones associated with clinical outcomes in patients receiving total body irradiation with ovarian shielding

Total body irradiation (TBI) with ovarian shielding is expected to preserve fertility among hematopoietic stem cell transplant (HSCT) patients with myeloablative TBI-based regimens. However, the radiation dose to the ovaries that preserves ovarian function in TBI remains poorly understood. Furthermore, it is uncertain whether the dose to the shielded organs is associated with relapse risk. Here, we retrospectively evaluated the relationship between fertility and the dose to the ovaries, and between relapse risk and the dose to the pelvic bones. A total of 20 patients (median age, 23 years) with standard-risk hematologic diseases were included. Median follow-up duration was 31.9 months. The TBI prescribed dose was 12 Gy in six fractions for three days. Patients’ ovaries were shielded with cylinder-type lead blocks. The dose–volume parameters (D_98% and D_mean) in the ovaries and the pelvic bones were extracted from the dose–volume histogram (DVH). The mean ovary D_mean for all patients was 2.4 Gy, and 18 patients recovered menstruation (90%). The mean ovary D_mean for patients with menstrual recovery and without recovery were 2.4 Gy and 2.4 Gy, respectively, with no significant difference (P = 0.998). Hematological relapse was observed in five patients. The mean pelvis D_mean and pelvis D_98% for relapse and non-relapse patients were 11.6 Gy and 11.7 Gy and 5.6 Gy and 5.3 Gy, respectively. Both parameters showed no significant difference (P = 0.827, 0.807). In conclusion, TBI with ovarian shielding reduced the radiation dose to the ovaries to 2.4 Gy, and preserved fertility without increasing the risk of relapse.     

Five-fraction CyberKnife radiotherapy for large brain metastases in critical areas: impact on the surrounding brain volumes circumscribed with a single dose equivalent of 14 Gy (V14) to avoid radiation necrosis

The efficacy and toxicity of five-fraction CyberKnife radiotherapy were evaluated in patients with large brain metastases in critical areas. A total of 85 metastases in 78 patients, including tumors >30 cm³ (4 cm in diameter) were treated with five-fraction CyberKnife radiotherapy with a median marginal dose of 31 Gy at a median prescribed isodose of 58%. Changes in the neurological manifestations, local tumor control, and adverse effects were investigated after treatment. The surrounding brain volumes circumscribed with 28.8 Gy (single dose equivalent to 14 Gy: V14) were measured to evaluate the risk of radiation necrosis. Neurological manifestations, such as motor weakness, visual disturbances and aphasia improved in 28 of 55 patients (50.9%). Local tumor control was obtained in 79 of 85 metastases (92.9%) during a median follow-up of eight months. Symptomatic edema occurred in 10 patients, and two of them (2.6%) required surgical resection because of radiation necrosis. The V14 of these patients was 3.0–19.7 cm³. There were 16 lesions with a V14 of ≥7.0 cm³, and two of these lesions developed extensive brain edema due to radiation necrosis. None of the patients with a V14 of <7.0 cm³ exhibited edema requiring surgical intervention. We therefore conclude that a high rate of local tumor control and low rates of complications can be obtained after five-fraction CyberKnife radiotherapy for large metastases in critical areas. The V14 of the surrounding brain is therefore a useful indicator for the risk of radiation necrosis in patients with large metastases.     

Three-fraction CyberKnife radiotherapy for brain metastases in critical areas: referring to the risk evaluating radiation necrosis and the surrounding brain volumes circumscribed with a single dose equivalence of 14 Gy (V14)

The efficacy and toxicity of three-fraction CyberKnife radiotherapy were evaluated in patients with brain metastases in critical areas. One hundred and fifty-nine metastases in 145 patients including tumors >10 cm³ were treated with three-fraction CyberKnife radiotherapy with a median marginal dose of 27 Gy at a median prescribed isodose of 60%. Changes in the neurological manifestations, local tumor control and adverse effects were investigated after treatment. The surrounding brain volumes circumscribed with 23.1 Gy (single dose equivalence of 14 Gy: V14) were measured to evaluate the risk of adverse effects. Neurological manifestations, such as motor weakness, visual disturbances and aphasia improved in 26 of 97 patients (26.8%). Local tumor control was obtained in 137 of 143 metastases (95.8%) during a median follow-up of 7 months. Nine patients had symptomatic edema and three of them (2.1%) required surgical resection because of radiation necrosis. The V14 of these patients was 4.6–31.5 cm³. There were 35 lesions with a V14 of 7 cm³ or more and three of them developed extensive brain edema due to radiation necrosis. None of the patients with a V14 of <7 cm³ exhibited edema requiring an operation. We therefore conclude that a high rate of local tumor control and low rates of complications are obtained after three-fraction CyberKnife radiotherapy for metastases in critical areas. The V14 of the surrounding brain therefore seems to be a useful indicator for the risk evaluation of radiation necrosis in patients with larger metastases.     

Radiation therapy for primary vaginal carcinoma

Brachytherapy plays a significant role in the management of cervical cancer, but the clinical significance of brachytherapy in the management of vaginal cancer remains to be defined. Thus, a single institutional experience in the treatment of primary invasive vaginal carcinoma was reviewed to define the role of brachytherapy. We retrospectively reviewed the charts of 36 patients with primary vaginal carcinoma who received definitive radiotherapy between 1992 and 2010. The treatment modalities included high-dose-rate intracavitary brachytherapy alone (HDR-ICBT; two patients), external beam radiation therapy alone (EBRT; 14 patients), a combination of EBRT and HDR-ICBT (10 patients), or high-dose-rate interstitial brachytherapy (HDR-ISBT; 10 patients). The median follow-up was 35.2 months. The 2-year local control rate (LCR), disease-free survival (DFS), and overall survival (OS) were 68.8%, 55.3% and 73.9%, respectively. The 2-year LCR for Stage I, II, III and IV was 100%, 87.5%, 51.5% and 0%, respectively (P = 0.007). In subgroup analysis consisting only of T2–T3 disease, the use of HDR-ISBT showed marginal significance for favorable 5-year LCR (88.9% vs 46.9%, P = 0.064). One patient each developed Grade 2 proctitis, Grade 2 cystitis, and a vaginal ulcer. We conclude that brachytherapy can play a central role in radiation therapy for primary vaginal cancer. Combining EBRT and HDR-ISBT for T2–T3 disease resulted in good local control.     

The clinical outcome of intracranial hemangioblastomas treated with linac-based stereotactic radiosurgery and radiotherapy

Recent publications have reported stereotactic radiosurgery as an effective and safe treatment for intracranial hemangioblastomas. However, because of the low incidence of these particular tumors, reports on large patient number studies have not yet been available. The objective of this study was to analyze the clinical results of 14 patients with 56 intracranial hemangioblastomas treated with linear accelerator (linac)-based stereotactic radiosurgery (SRS) and radiotherapy (SRT) in the same institute. The median age of patients was 41 years (range, 28–73 years). Nine of the patients (64%) had von Hippel-Lindau disease. A total of 39 lesions (70%) were treated with CyberKnife (CK), and 17 lesions (30%) were treated with X-Knife. The median pretreatment volume was 0.26 cm³ (range, 0.026–20.4 cm³). The median marginal dose was 20 Gy (range, 10–32 Gy) in 1 fraction (range, 1–10 fractions). The median follow-up time was 24 months (range, 11–89 months). At the last follow-up, 47 tumors (84%) were stable, 7 (13%) decreased and 2 (4%) increased. The 1-, 2- and 6-year local control rates were 98%, 88% and 73%, respectively. No radiation complications were observed in this study. There was a trend toward local failure only in cystic tumors, but this trend was not found to be statistically significant. SRS/SRT achieved a high local control rate in intracranial hemangioblastomas without radiation-induced complications.     

Radiation therapy for carcinoma of the uterine cervix: comparison of two brachytherapy schedules

We compared the survival rates and late effects for two groups of cervical cancer patients treated with almost the same external radiotherapy but different remote afterloading systems (RALS) for high-dose-rate intracavitary radiation therapy regimens. A total of 218 patients with carcinoma of the uterine cervix were treated. For 98 patients, intracavitary brachytherapy was delivered with 6–7.5 Gy/fraction to Point A (Group A), and for 120, 5 Gy/fraction with a modified source step size (Group B). The 3-year cause-specific survival rates by stage and treatment schedule were Group A: 91% and Group B: 96% in Stage I, 89% and 92% in Stage II, 64% and 75% in Stage III, 44% and 69% in Stage IV. The survival curves did not reveal any statistically significant differences at any stage. The 3-year cumulative local failure rates were 14% in Group A and 7% in Group B (P = 0.1202), while the actuarial rates of developing rectal complication (Grade 2 or more) at 3 years were 25% in Group A and 4% in Group B (P < 0.0001). This retrospective analysis suggests that a low dose per fraction with modified source step size is advantageous because of yielding almost the same local control but with fewer rectal complications.     

External beam boost irradiation for clinically positive pelvic nodes in patients with uterine cervical cancer

The purpose of this study was to retrospectively analyze the treatment results of boost external beam radiotherapy (EBRT) to clinically positive pelvic nodes in patients with uterine cervical cancer. The study population comprised 174 patients with FIGO stages 1B1–4A cervical cancer who were treated with definitive radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) and high-dose-rate intracavitary brachytherapy (HDR-ICBT). Patients with positive para-aortic or common iliac nodes (≥10 mm in the shortest diameter, as evaluated by CT/MRI) were ineligible for the study. Fifty-seven patients (33%) had clinically positive pelvic nodes. The median maximum diameter of the nodes was 15 mm (range, 10–60 mm) and the median number of positive lymph nodes was two (range, one to four). Fifty-two of 57 patients (91%) with positive nodes were treated with boost EBRT (6–10 Gy in three to five fractions). The median prescribed dose of EBRT for nodes was 56 Gy. The median follow-up time for all patients was 66 months (range, 3–142 months). The 5-year overall survival rate, disease-free survival rate and pelvic control rate for patients with positive and negative nodes were 73% and 92% (P = 0.001), 58% and 84% (P < 0.001), and 83% and 92% (P = 0.082), respectively. Five of 57 node-positive patients (9%) developed pelvic node recurrences. All five patients with nodal failure had concomitant cervical failure and/or distant metastases. No significant difference was observed with respect to the incidence or severity of late complications by application of boost EBRT. The current retrospective study demonstrated that boost EBRT to positive pelvic nodes achieves favorable nodal control without increasing late complications.     

Final results from a multicenter prospective study (?JROSG 05–5) on postoperative radiotherapy for patients with ductal carcinoma in situ with an involved surgical margin or close margin widths of 1 mm or less

This multicenter prospective study ( Japanese Radiation Oncology Study Group: JROSG 05-5) aimed to evaluate the effectiveness of postoperative radiotherapy (PORT) in patients with ductal carcinoma in situ (DCIS) with an involved surgical margin or close margin widths of ≤1 mm or less. PORT consisted of whole-breast irradiation (50 Gy in 25 fractions) followed by boost irradiation (10 Gy in 5 fractions). Eligibility criteria were as follows: (i) DCIS without an invasive carcinoma component, (ii) age between 20 and 80 years old, (iii) involved margin or close margin widths of ≤1 mm, (iv) refusal of re-resection, (v) performance status of 0–2, and (vi) written informed consent. The primary endpoint was ipsilateral breast tumor recurrence (IBTR), and secondary endpoints were overall survival (OS), relapse-free survival (RFS), recurrence patterns, and adverse events. A total of 37 patients from 12 institutions were enrolled from January 2007 to May 2009. The median follow-up time was 62 months (range, 28–85 months). The median pathological tumor size was 2.5 cm (range, 0.3–8.5 cm). Of the 37 patients, 21 had involved margins, and 16 had close margins. The 5-year IBTR, OS and RFS rates were 6% (95% confidence interval [CI]: 2–21), 97% (95% CI: 83–99) and 91% (95% CI: 77–97), respectively. Two patients developed local recurrence at the original site after 39 and 58 months. No severe adverse events were found. Our study suggests that this PORT regimen could be a treatment option for patients with DCIS with involved margin or close margin who don''t desire re-resection.     

Alternating chemoradiotherapy in patients with nasopharyngeal cancer: prognostic factors and proposal for individualization of therapy

The purpose of this study is to assess the efficacy of alternating chemoradiation in patients with nasopharyngeal cancer. From 1990–2006, 100 patients with nasopharyngeal cancer were treated with alternating chemoradiation at the Aichi Cancer Center. Of these, 4, 2, 23, 34, 13 and 23 patients were staged as I, IIA, IIB, III, IVA and IVB, respectively. The median radiation doses for primary tumors and metastatic lymph nodes were 66.6 Gy (range, 50.4–80.2 Gy) and 66 Gy (range, 40.4–82.2 Gy), respectively. A total of 82 patients received chemotherapy with both cisplatin and 5-fluorouracil (5-FU), while 14 patients received nedaplatin (CDGP) and 5-FU. With a median follow-up of 65.9 months, the 5-year rates of overall survival (OAS) and progression-free survival (PFS) were 78.1% and 68.3%, respectively. On multivariate analysis (MVA), elderly age, N3, and WHO type I histology proved to be significantly unfavorable prognostic factors of OAS. As for PFS, there were T4, N3, and WHO type I histology in MVA. Acute toxicities of hematologic and mucositis/dermatitis ≥ Grade 3 were relatively high (32%); however, they were well-managed. Late toxicities of ≥ Grade 3 were three (3%) mandibular osteomyelitis and one (1%) lethal mucosal bleeding. Results for alternating chemoradiation for nasopharyngeal carcinoma are promising. In order to improve outcomes, usage of intensity-modulated radiation therapy and application of active anticancer agents are hopeful treatments, especially for groups with poor prognosis factors with WHO type I histopathology, T4 and/or N3 disease.     

Prognostic significance of inflammatory response markers for locally advanced squamous cell carcinoma of the external auditory canal and middle ear

We investigated the prognostic significance and treatment outcomes of pretreatment inflammatory response markers for locally advanced squamous cell carcinoma (SCC) of the external auditory canal (EAC) and middle ear (ME). Between July 2003 and July 2019, 21 patients with SCC of the EAC (n = 18) or ME (n = 3) who received radiotherapy with or without surgery or systemic therapy (radiotherapy alone [n = 2], radiotherapy + systemic therapy [n = 6], radiotherapy + surgery [n = 7], radiotherapy + surgery + systemic therapy [n = 6]) were retrospectively examined. The median radiation dose was 66.0 (range, 50.4–70.0) Gy, with daily fractions of 1.8–2.0 Gy. The median follow-up period was 25 months (range, 6–137). The two-year overall survival (OS), progression-free survival (PFS), and locoregional control (LC) rates were 61%, 48%, and 55%, respectively. OS, PFS, and LC did not differ significantly according to patient- (age, sex), tumor- (Pittsburgh stage, pretreatment neurological findings), and treatment-related (surgery or systemic therapy, radiation dose, prophylactic neck irradiation) factors. Conversely, there were significant differences in OS, PFS, and LC between patients with high and low pretreatment C-reactive protein-to-albumin ratios (p = 0.002, 0.003, and 0.004, respectively). OS also differed significantly between patients with high and low pretreatment neutrophil-to-lymphocyte ratios (NLR; p = 0.037). Other inflammatory response markers, including platelet-to-lymphocyte ratio (PLR) and albumin-to-globulin ratio (AGR), did not influence OS, PFS, or LC. Our findings suggest that pretreatment C-reactive protein-to-albumin ratio and NLRs have a significant impact on treatment outcomes in patients with locally advanced SCC of the EAC and ME.     

Preoperative chemoradiotherapy for locally advanced low rectal cancer using intensity-modulated radiotherapy to spare the intestines: a single-institutional pilot trial

The irradiated volume of intestines is associated with gastrointestinal toxicity in preoperative chemoradiotherapy for rectal cancer. The current trial prospectively explored how much of the irradiated volume of intestines was reduced by intensity-modulated radiotherapy (IMRT) compared with 3-dimensional conformal radiotherapy (3DCRT) and whether IMRT might alleviate the acute gastrointestinal toxicity in this population. The treatment protocol encompassed preoperative chemoradiotherapy using IMRT plus surgery for patients with clinical T3–4, N0–2 low rectal cancer. IMRT delivered 45 Gy per 25 fractions for gross tumors, mesorectal and lateral lymph nodal regions, and tried to reduce the volume of intestines receiving 15 Gy (V_{15 Gy}) < 120 cc and V_{45 Gy} ≤ 0 cc, respectively, while keeping target coverage. S-1 and irinotecan were concurrently administered. Acute gastrointestinal toxicity, rates of clinical downstaging, sphincter preservation, local regional control (LRC) and overall survival (OS) were evaluated. Twelve enrolled patients completed the chemoradiotherapy protocol. The volumes of intestines receiving medium to high doses were reduced by the current IMRT protocol compared to 3DCRT; however, the predefined constraint of V_{15 Gy} was met only in three patients. The rate of ≥ grade 2 gastrointestinal toxicity excluding anorectal symptoms was 17%. The rates of clinical downstaging, sphincter preservation, three-year LRC and OS were 75%, 92%, 92% and 92%, respectively. In conclusion, preoperative chemoradiotherapy using IMRT for this population might alleviate acute gastrointestinal toxicity, achieving high LRC and sphincter preservation; although further advancement is required to reduce the irradiated volume of intestines, especially those receiving low doses.     

Toxicity and efficacy of three dose-fractionation regimens of intensity-modulated radiation therapy for localized prostate cancer

Outcomes of three protocols of intensity-modulated radiation therapy (IMRT) for localized prostate cancer were evaluated. A total of 259 patients treated with 5-field IMRT between 2005 and 2011 were analyzed. First, 74 patients were treated with a daily fraction of 2.0 Gy to a total of 74 Gy (low risk) or 78 Gy (intermediate or high risk). Then, 101 patients were treated with a 2.1-Gy daily fraction to 73.5 or 77.7 Gy. More recently, 84 patients were treated with a 2.2-Gy fraction to 72.6 or 74.8 Gy. The median patient age was 70 years (range, 54–82) and the follow-up period for living patients was 47 months (range, 18–97). Androgen deprivation therapy was given according to patient risk. The overall and biochemical failure-free survival rates were, respectively, 96 and 82% at 6 years in the 2.0-Gy group, 99 and 96% at 4 years in the 2.1-Gy group, and 99 and 96% at 2 years in the 2.2-Gy group. The biochemical failure-free rate for high-risk patients in all groups was 89% at 4 years. Incidences of Grade ≥2 acute genitourinary toxicities were 9.5% in the 2.0-Gy group, 18% in the 2.1-Gy group, and 15% in the 2.2-Gy group (P = 0.29). Cumulative incidences of Grade ≥2 late gastrointestinal toxicity were 13% in the 2.0-Gy group at 6 years, 12% in the 2.1-Gy group at 4 years, and 3.7% in the 2.2-Gy group at 2 years (P = 0.23). So far, this stepwise shortening of treatment periods seems to be successful.     

Prognostic factors associated with radiotherapy for cervical cancer with computed tomography-detected para-aortic lymph node metastasis

Patients with cervical cancer diagnosed with a para-aortic lymph node (PALN) metastasis by computed tomography (CT) scan were analyzed to identify associated prognostic factors. A total of 55 patients were reviewed, and 27 of these patients underwent extended-field radiotherapy (EFRT). The median PALN dose in patients receiving EFRT was 45 Gy (range, 27–57.6 Gy). Of the 55 patients, 28 underwent pelvic radiotherapy (RT); concurrent chemoradiotherapy (CCRT) was administered to 41 patients. The Kaplan–Meier method was used to calculate the actuarial rate. Multivariate analysis was performed using the Cox proportional hazards model. Five-year overall survival (OS) rates were 41% and 17.9% in patients undergoing EFRT and pelvic RT (P = 0.030), respectively. Age < 53 years (P = 0.023), FIGO Stage I–II (P = 0.002), and treatment with EFRT (P = 0.003) were independent predictors of better OS. The use of CCRT (P = 0.014), Stage I–II (P = 0.002), and treatment using EFRT (P = 0.036) were independent predictors of distant metastasis. In patients undergoing EFRT plus CCRT, the 5-year OS was 50%. Three-year PALN disease-free rates were 8.8%, 57.9% and 100% (P < 0.001) in CCRT patients who received PALN doses of 0 Gy, ≤45 Gy and ≥50.4 Gy, respectively. Although PALN metastasis is thought to be distant metastasis in cervical cancer, EFRT plus CCRT shows a good outcome, particularly in younger patients in an early FIGO stage. Cervical cancer with a PALN metastasis should not be considered incurable. Doses ≥50.4 Gy for treating PALN may result in better disease control.     

Results and DVH analysis of late rectal bleeding in patients treated with 3D-CRT or IMRT for localized prostate cancer

In patients undergoing radiotherapy for localized prostate cancer, dose–volume histograms and clinical variables were examined to search for correlations between radiation treatment planning parameters and late rectal bleeding. We analyzed 129 patients with localized prostate cancer who were managed from 2002 to 2010 at our institution. They were treated with 3D conformal radiation therapy (3D-CRT, 70 Gy/35 fractions, 55 patients) or intensity-modulated radiation therapy (IMRT, 76 Gy/38 fractions, 74 patients). All radiation treatment plans were retrospectively reconstructed, dose–volume histograms of the rectum were generated, and the doses delivered to the rectum were calculated. Time to rectal bleeding ranged from 9–53 months, with a median of 18.7 months. Of the 129 patients, 33 patients had Grade 1 bleeding and were treated with steroid suppositories, while 25 patients with Grade 2 bleeding received argon plasma laser coagulation therapy (APC). Three patients with Grade 3 bleeding required both APC and blood transfusion. The 5-year incidence rate of Grade 2 or 3 rectal bleeding was 21.8% for the 3D-CRT group and 21.6% for the IMRT group. Univariate analysis showed significant differences in the average values from V65 to V10 between Grades 0–1 and Grades 2–3. Multivariate analysis demonstrated that patients with V65 ≥ 17% had a significantly increased risk (P = 0.032) of Grade 2 or 3 rectal bleeding. Of the 28 patients of Grade 2 or 3 rectal bleeding, 17 patients (60.7%) were cured by a single session of APC, while the other 11 patients required two sessions. Thus, none of the patients had any further rectal bleeding after the second APC session.     

Prognosis was not deteriorated by multiple primary cancers in esophageal cancer patients treated by radiotherapy

Esophageal cancer patients are often associated with multiple primary cancers (MPC). The aim of this study is to evaluate the effect of MPC on prognosis in esophageal cancer patients treated by radiotherapy. Between 2001 and 2008, esophageal cancer patients treated by definitive radiotherapy at Gunma Cancer Center were retrospectively reviewed. Exclusion criteria were preoperative or postoperative radiotherapy, palliative radiotherapy, follow-up of <6 months, radiation dose of <50 Gy and no information on MPC. We analyzed 167 esophageal cancer patients and 56 (33.5%) were associated with MPC. Gastric cancer was the most frequent tumor (38.2%), followed by head and neck cancer (26.5%). Median follow-up time was 31.5 months (range 6.1–87.3 months). Patients with MPC included more stage I/II esophageal cancer than those without MPC (66.1% vs. 36.9%, P < 0.01). The 5-year overall survival rate for esophageal cancer with MPC was relatively better than those without MPC (46.1% vs. 26.7%), although the difference did not reach statistical significance in univariate analysis (P = 0.09). Stage I/II esophageal cancer patients had a significantly better overall survival than stage III/IV patients (P < 0.01). Among esophageal cancer patients with MPC, there was no difference in overall survival between antecedent and synchronous cancer (P = 0.59). Our study indicated that the prognosis of esophageal cancer patients treated by radiotherapy was primarily determined by the clinical stage itself, but not the presence of MPC.     

Clinical results of stereotactic body radiotherapy for Stage I small-cell lung cancer: a single institutional experience

The purpose of this study was to evaluate the treatment outcomes of stereotactic body radiotherapy (SBRT) for Stage I small-cell lung cancer (SCLC). From April 2003 to September 2009, a total of eight patients with Stage I SCLC were treated with SBRT in our institution. In all patients, the lung tumors were proven as SCLC pathologically. The patients'' ages were 58–84 years (median: 74). The T-stage of the primary tumor was T1a in two, T1b in two and T2a in four patients. Six of the patients were inoperable because of poor cardiac and/or pulmonary function, and two patients refused surgery. SBRT was given using 7–8 non-coplanar beams with 48 Gy in four fractions. Six of the eight patients received 3–4 cycles of chemotherapy using carboplatin (CBDCA) + etoposide (VP-16) or cisplatin (CDDP) + irinotecan (CPT-11). The follow-up period for all patients was 6–60 months (median: 32). Six patients were still alive without any recurrence. One patient died from this disease and one died from another disease. The overall and disease-specific survival rate at three years was 72% and 86%, respectively. There were no patients with local progression of the lesion targeted by SBRT. Only one patient had nodal recurrence in the mediastinum at 12 months after treatment. The progression-free survival rate was 71%. No Grade 2 or higher SBRT-related toxicities were observed. SBRT plus chemotherapy could be an alternative to surgery with chemotherapy for inoperable patients with Stage I small-cell lung cancer. However, further investigation is needed using a large series of patients.     

Analysis of late toxicity associated with external beam radiation therapy for prostate cancer with uniform setting of classical 4-field 70 Gy in 35 fractions: a survey study by the Osaka Urological Tumor Radiotherapy Study Group

We aimed to analyse late toxicity associated with external beam radiation therapy (EBRT) for prostate cancer using uniform dose-fractionation and beam arrangement, with the focus on the effect of 3D (CT) simulation and portal field size. We collected data concerning patients with localized prostate adenocarcinoma who had been treated with EBRT at five institutions in Osaka, Japan, between 1998 and 2006. All had been treated with 70 Gy in 35 fractions, using the classical 4-field technique with gantry angles of 0°, 90°, 180° and 270°. Late toxicity was evaluated strictly in terms of the Common Terminology Criteria for Adverse Events Version 4.0. In total, 362 patients were analysed, with a median follow-up of 4.5 years (range 1.0–11.6). The 5-year overall and cause-specific survival rates were 93% and 96%, respectively. The mean ± SD portal field size in the right–left, superior–inferior, and anterior–posterior directions was, respectively, 10.8 ± 1.1, 10.2 ± 1.0 and 8.8 ± 0.9 cm for 2D simulation, and 8.4 ± 1.2, 8.2 ± 1.0 and 7.7 ± 1.0 cm for 3D simulation (P < 0.001). No Grade 4 or 5 late toxicity was observed. The actuarial 5-year Grade 2–3 genitourinary and gastrointestinal (GI) late toxicity rates were 6% and 14%, respectively, while the corresponding late rectal bleeding rate was 23% for 2D simulation and 7% for 3D simulation (P < 0.001). With a uniform setting of classical 4-field 70 Gy/35 fractions, the use of CT simulation and the resultant reduction in portal field size were significantly associated with reduced late GI toxicity, especially with less rectal bleeding.     

Radiotherapy with fraction size of 2.25 Gy in T1-2 laryngeal and hypopharyngeal cancer

This study was carried out to evaluate the influence of fraction size 2.25 Gy on local control of T1 and T2 laryngeal and hypopharyngeal cancers. Between August 2002 and December 2010, 80 patients with T1 and T2 laryngeal or hypopharyngeal cancers were treated with definitive radiotherapy with a fraction size of 2.25 Gy. Primary sites were the larynx in 69 and the hypopharynx in 11. Fifty-three patients were T1 and 27 were T2. All patients'' pathology was squamous cell carcinoma except one carcinosarcoma. Radiotherapy was delivered 5 days/week with a 4-MV photon beam up to a total dose of 63.0 Gy. Median treatment time was 41 days. Statistical analysis of survival was calculated using the Kaplan–Meier method. No acute toxicity greater than grade 2 (CTCAE ver. 3.0.) including mucositis and dermatitis was observed. All but one patient had a complete response. The partial response patient received salvage surgery. The median follow-up period was 47 months (ranging from 4 to 108 months). No late toxicity greater than 1 was observed. Nine patients developed recurrence, seven local and two neck lymph nodes. Three patients died, one from laryngeal cancer and two from intercurrent diseases. The 5-year local control rates (LCRs) in the entire group, larynx T1, larynx T2 and hypopharynx T1 were 85.8%, 97.6%, 70.1% and 85.7%, respectively. The LCRs of T1 improved compared with our historical control, but not those of T2. The 2.25-Gy fraction size is safe and may have the potential to achieve good LCR in T1 lesions.