Comparison of intensity-modulated radiotherapy with the 5-field technique,helical tomotherapy and volumetric modulated arc therapy for localized prostate cancer

The outcomes of three methods of intensity-modulated radiation therapy (IMRT) for localized prostate cancer were evaluated. Between 2010 and 2018, 308 D’Amico intermediate- or high-risk patients were treated with 2.2 Gy daily fractions to a total dose of 74.8 Gy in combination with hormonal therapy. Overall, 165 patients were treated with 5-field IMRT using a sliding window technique, 66 were then treated with helical tomotherapy and 77 were treated with volumetric modulated arc therapy (VMAT). The median age of patients was 71 years. The median follow-up period was 75 months. Five-year overall survival (OS) and biochemical or clinical failure-free survival (FFS) rates were 95.5 and 91.6% in the 5-field IMRT group, 95.1 and 90.3% in the tomotherapy group and 93.0 and 88.6% in the VMAT group, respectively, with no significant differences among the three groups. The 5-year cumulative incidence of late grade ≥2 genitourinary and gastrointestinal toxicities were 7.3 and 6.2%, respectively, for all patients. Late grade ≥2 gastrointestinal toxicities were less frequent in patients undergoing VMAT (0%) than in patients undergoing 5-field IMRT (7.3%) and those undergoing tomotherapy (11%) (P = 0.025), and this finding appeared to be correlated with the better rectal DVH parameters in patients undergoing VMAT. Other toxicities did not differ significantly among the three groups, although bladder dose-volume parameters were slightly worse in the tomotherapy group than in the other groups. Despite differences in the IMRT delivery methods, X-ray energies and daily registration methods, all modalities may be used as IMRT for localized prostate cancer.     

Preliminary analysis of risk factors for late rectal toxicity after helical tomotherapy for prostate cancer

The purpose of this study is to examine risk factors for late rectal toxicity for localized prostate cancer patients treated with helical tomotherapy (HT). The patient cohort of this retrospective study was composed of 241 patients treated with HT and followed up regularly. Toxicity levels were scored according to the Radiation Therapy Oncology Group grading scale. The clinical and dosimetric potential factors increasing the risk of late rectal toxicity, such as age, diabetes, anticoagulants, prior abdominal surgery, prescribed dose, maximum dose of the rectum, and the percentage of the rectum covered by 70 Gy (V70), 60 Gy (V60), 40 Gy (V40) and 20 Gy (V20) were compared between ≤ Grade 1 and ≥ Grade 2 toxicity groups using the Student''s t-test. Multivariable logistic regression analysis of the factors that appeared to be associated with the risk of late rectal toxicity (as determined by the Student''s t-test) was performed. The median follow-up time was 35 months. Late Grade 2–3 rectal toxicity was observed in 18 patients (7.4%). Age, the maximum dose of the rectum, V70 and V60 of the ≥ Grade 2 toxicity group were significantly higher than in those of the ≤ Grade 1 toxicity group (P = 0.00093, 0.048, 0.0030 and 0.0021, respectively). No factor was significant in the multivariable analysis. The result of this study indicates that the risk of late rectal toxicity correlates with the rectal volume exposed to high doses of HT for localized prostate cancer. Further follow-up and data accumulation may establish dose–volume modeling to predict rectal complications after HT.     

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.     

前列腺癌调强适形放疗的临床疗效和副反应分析

目的:分析调强适形放疗治疗前列腺癌的临床疗效及副反应。方法:回顾性分析25例接受调强适形放射治疗的前列腺癌患者资料,12例患者前列腺精囊95%PTV处方剂量为70Gy。13例患者前列腺精囊95%PTV处方剂量为78Gy,盆腔淋巴引流区处方剂量50Gy。结果:完全缓解9例,部分缓解8例,稳定8例,1、3年总生存率分别为100.0%和96.0%。早期胃肠道副反应1级15例,2级9例。早期泌尿系统反应1级12例,2级6例。晚期胃肠道副反应1级5例,2级4例。晚期泌尿系副反应1级3例,2级3例。结论:调强适形放疗提高了前列腺肿瘤靶区剂量,前列腺周围正常组织和器官放疗副反应发生率低,患者可获得较好的放疗耐受性。     

Transitioning from conventional radiotherapy to intensity-modulated radiotherapy for localized prostate cancer: changing focus from rectal bleeding to detailed quality of life analysis

With the advent of modern radiation techniques, we have been able to deliver a higher prescribed radiotherapy dose for localized prostate cancer without severe adverse reactions. We reviewed and analyzed the change of toxicity profiles of external beam radiation therapy (EBRT) from the literature. Late rectal bleeding is the main adverse effect, and an incidence of >20% of Grade ≥2 adverse events was reported for 2D conventional radiotherapy of up to 70 Gy. 3D conformal radiation therapy (3D-CRT) was found to reduce the incidence to ∼10%. Furthermore, intensity-modulated radiation therapy (IMRT) reduced it further to a few percentage points. However, simultaneously, urological toxicities were enhanced by dose escalation using highly precise external radiotherapy. We should pay more attention to detailed quality of life (QOL) analysis, not only with respect to rectal bleeding but also other specific symptoms (such as urinary incontinence and impotence), for two reasons: (i) because of the increasing number of patients aged >80 years, and (ii) because of improved survival with elevated doses of radiotherapy and/or hormonal therapy; age is an important prognostic factor not only for prostate-specific antigen (PSA) control but also for adverse reactions. Those factors shift the main focus of treatment purpose from survival and avoidance of PSA failure to maintaining good QOL, particularly in older patients. In conclusion, the focus of toxicity analysis after radiotherapy for prostate cancer patients is changing from rectal bleeding to total elaborate quality of life assessment.     

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.     

Soy isoflavones in conjunction with radiation therapy in patients with prostate cancer

Soy isoflavones sensitize prostate cancer cells to radiation therapy by inhibiting cell survival pathways activated by radiation. At the same time, soy isoflavones have significant antioxidant and anti-inflammatory activity, which may help prevent the side effects of radiation. Therefore, we hypothesized that soy isoflavones could be useful when given in conjunction with curative radiation therapy in patients with localized prostate cancer. In addition to enhancing the efficacy of radiation therapy, soy isoflavones could prevent the adverse effects of radiation. We conducted a pilot study to investigate the effects of soy isoflavone supplementation on acute and subacute toxicity (≤6 mo) of external beam radiation therapy in patients with localized prostate cancer. Forty-two patients with prostate cancer were randomly assigned to receive 200 mg soy isoflavone (Group 1) or placebo (Group 2) daily for 6 mo beginning with the first day of radiation therapy, which was administered in 1.8 to 2.5 Gy fractions for a total of 73.8 to 77.5 Gy. Adverse effects of radiation therapy on bladder, bowel, and sexual function were assessed by a self-administered quality of life questionnaire at 3 and 6 mo. Only 26 and 27 patients returned completed questionnaires at 3 and 6 mo, respectively. At each time point, urinary, bowel, and sexual adverse symptoms induced by radiation therapy were decreased in the soy isoflavone group compared to placebo group. At 3 mo, soy-treated patients had less urinary incontinence, less urgency, and better erectile function as compared to the placebo group. At 6 mo, the symptoms in soy-treated patients were further improved as compared to the placebo group. These patients had less dripping/leakage of urine (7.7% in Group 1 vs. 28.4% in Group 2), less rectal cramping/diarrhea (7.7% vs. 21.4%), and less pain with bowel movements (0% vs. 14.8%) than placebo-treated patients. There was also a higher overall ability to have erections (77% vs. 57.1%). The results suggest that soy isoflavones taken in conjunction with radiation therapy could reduce the urinary, intestinal, and sexual adverse effects in patients with prostate cancer.     

Neoadjuvant capecitabine,bevacizumab and radiotherapy for locally advanced rectal cancer: results of a single-institute Phase I study

The aim of this Phase I clinical trial was to assess the feasibility and safety of capecitabine-based preoperative chemoradiotherapy (CRT) combined with bevacizumab and to determine the optimal capecitabine dose for Japanese patients with locally advanced rectal cancer. Patients with cT3/T4 rectal cancer were eligible. Bevacizumab was administered at 5 mg/kg intravenously on Days 1, 15 and 29. Capecitabine was administered on weekdays concurrently with pelvic radiotherapy at a daily dose of 1.8 Gy, totally to 50.4 Gy. Capecitabine was initiated at 825 mg/m² twice daily at Dose Level 1, with a planned escalation to 900 mg/m² twice daily at Dose Level 2. Within 6.1–10.3 (median, 9.4) weeks after the completion of the CRT, surgery was performed. Three patients were enrolled at each dose level. Regarding the CRT-related acute toxicities, all of the adverse events were limited to Grade 1. There was no Grade 2 or greater toxicity. No patient needed attenuation or interruption of bevacizumab, capecitabine or radiation. All of the patients received the scheduled dose of CRT. All of the patients underwent R0 resection. Two (33.3%) of the six patients had a pathological complete response, and five (83.3%) patients experienced downstaging. In total, three patients (50%) developed postoperative complications. One patient developed an intrapelvic abscess and healed with incisional drainage. The other two patients healed following conservative treatment. This regimen was safely performed as preoperative CRT for Japanese patients with locally advanced rectal cancer. The recommended capecitabine dose is 900 mg/m² twice daily.     

Neoadjuvant short-course hyperfractionated accelerated radiotherapy (SC-HART) combined with S-1 for locally advanced rectal cancer

The purpose of this study was to examine the safety and feasibility of a novel protocol of neoadjuvant short-course hyperfractionated accelerated radiotherapy (SC-HART) combined with S-1 for locally advanced rectal cancer. A total of 56 patients with lower rectal cancer of cT3N1M0 (Stage III b) was treated with SC-HART followed by radical surgery, and were analyzed in the present study. SC-HART was performed with a dose of 2.5 Gy twice daily, with an interval of at least 6 hours between fractions, up to a total dose of 25 Gy (25 Gy in 10 fractions for 5 days) combined with S-1 for 10 days. Radical surgery was performed within three weeks following the end of the SC-HART. The median age was 64.6 (range, 39–85) years. The median follow-up term was 16.3 (range, 2–53) months. Of the 56 patients, 53 (94.4%) had no apparent adverse events before surgery; 55 (98.2%) completed the full course of neoadjuvant therapy, while one patient stopped chemotherapy because of Grade 3 gastrointestinal toxicity (CTCAE v.3). The sphincter preservation rate was 94.6%. Downstaging was observed in 45 patients (80.4%). Adjuvant chemotherapy was administered to 43 patients (76.8%). The local control rate, disease-free survival rate and disease-specific survival rate were 100%, 91.1% and 100%, respectively. To conclude, SC-HART combined with S-1 for locally advanced rectal cancer was well tolerated and produced good short-term outcomes. SC-HART therefore appeared to have a good feasibility for use in further clinical trials.     

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.     

125Iodine monotherapy for Japanese men with low- and intermediate-risk prostate cancer: outcomes after 5 years of follow-up

Data from 305 Japanese men with low-risk (n = 175) or intermediate-risk (n = 130) prostate cancer who underwent ¹²⁵I monotherapy were retrospectively analyzed. Of the 305 patients, 93 received hormonal therapy for a median of 6 months (range, 1–33 months) before implantation. The prescribed dose to the prostate plus 3- to 5-mm margin was set at 145 Gy. The mean dose to 90% of the prostate volume at 1 month (D90) and the prostate volume receiving at least 100% dose at 1 month (V100) were 173.4 Gy and 95.8%, respectively. The median follow-up was 66 months (range, 12–94 months). The 5-year biochemical non-evidence of disease rate was 95.5% (low-risk, 94.2%; intermediate-risk, 97.3%). The 5-year freedom from clinical failure rate was 98.9% (low-risk, 98.9%; intermediate-risk, 99.2%).The initial prostate-specific antigen level was identified as a significant predictive factor for biochemical recurrence (P = 0.029). The late Grade 3 genitourinary toxicity rate was 2.0%. No patients displayed late gastrointestinal toxicity of Grade 3 or worse. Monotherapy with ¹²⁵I showed excellent outcomes with limited morbidity for Japanese men with low- and intermediate-risk prostate cancer after 5 years of follow-up.     

Local tumor control and (disease-free) survival after surgery with pre- and intraoperative radiotherapy for primary non-resectable rectal carcinoma and local recurrence

OBJECTIVE: Survey of the results of multimodality treatment for primary irresectable rectum carcinoma and local recurrence of rectal cancer. DESIGN: Retrospective. METHODS: During the period 1 February 1994 to 31 August 1999, 43 patients with locally advanced primary rectal cancer (25 men and 18 women; mean age: 64 years (range: 36-86)) and 53 patients with a local recurrence (33 men and 20 women; mean age: 61 years (39-82)) were treated with a multimodality treatment: i.e. preoperative radiotherapy (doses 50.4 Gy, or 30.0 Gy in the case of reirradiation), extensive surgery and intraoperative radiotherapy (doses 10-17.5 Gy). This treatment took place at two hospitals in the Netherlands, the Catharina Hospital in Eindhoven and, since 1997, the Daniel den Hoed Cancer Centre in Rotterdam. In 2000 data were collected for the local control and (disease-free) survival; these were analysed using the Kaplan-Meier method. Patients also completed a questionnaire about the quality of life at a median period of 14 months (range: 4-60) after the operation; the response level was 96% (76/79). RESULTS: After 3 years, the local control, disease-free survival and survival rates for the locally advanced primary rectal cancer group were 74%, 60% and 55% respectively, and for the locally recurrent rectal cancer group 64%, 34% and 50% respectively. Tumour resection with microscopically negative margins had a statistically significant positive effect on the local control and disease-free survival in both groups as well as on the survival in the locally advanced primary patient group. Seven of the 96 patients (7%) died as a result of complications. Of the patients with a primary irresectable carcinoma or a local recurrent tumour who completed the questionnaire the results were as follows: 56% and 63% respectively had been able to resume employment, 53% and 59% respectively had been able to resume their previous lifestyle, 15% and 27% respectively indicated radicular pain as a new symptom, 26% and 46% respectively stated problems with walking, 42% and 44% respectively stated problems with urinating and 59% and 52% respectively a reduction in sexual activity.     

同步新辅助放化疗联合全根治性切除治疗中低位局部进展期直肠癌的探索研究

目的：探讨同步新辅助放化疗联合全直肠系膜切除术（TME）治疗中低位局部进展期直肠癌的可行性及安全性。方法：选取2013年6月-2014年6月本院23例中低位局部进展期直肠癌患者,Ⅱ期（T3-4No Mo）11例,Ⅲ期（T1-4N1-2Mo）12例,均接受术前同步新辅助放化疗（术前放疗总剂量全盆腔DT 40-46Gy/20-23 Fx,瘤床区加量至50-56 Gy/25-28 Fx;化疗采用含希罗达方案2个周期）。同步新辅助放化疗结束后4-8周行手术治疗,遵循TME原则,并尽可能保肛。结果：22例患者均完成同步新辅助放化疗,放化疗期间3级毒副反应总发生率为27.3%,无4级毒副反应者。放化疗后CR 2例、PR 14例、SD 4例;16例（80%）患者的临床TNM分期下降。同步新辅助放化疗结束后4-8周,20例患者行根治性手术治疗,其中12例行低位或超低位前切除术（Dixon术）,7例行腹会阴联合切除术（Miles术）,1例行Hartmann手术,保肛率为60.0%（12/20）。无一例发生围手术期死亡,术后并发症的总发生率为20%（4/20）。结论：同步新辅助放化疗联合TME治疗中低位局部进展期直肠癌安全而有效,可以降低肿瘤分期、提高肿瘤切除率和保肛率,改善患者的生活质量。     

Whole-pelvic volumetric-modulated arc therapy for high-risk prostate cancer: treatment planning and acute toxicity

The objectives of this study were to evaluate dosimetric quality and acute toxicity of volumetric-modulated arc therapy (VMAT) and daily image guidance in high-risk prostate cancer patients. A total of 100 consecutive high-risk prostate cancer patients treated with definitive VMAT with prophylactic whole-pelvic radiotherapy (WPRT) were enrolled. All patients were treated with a double-arc VMAT plan delivering 52 Gy to the prostate planning target volume (PTV), while simultaneously delivering 46.8 Gy to the pelvic nodal PTV in 26 fractions, followed by a single-arc VMAT plan delivering 26 Gy to the prostate PTV in 13 fractions. Image-guided RT was performed with daily cone-beam computed tomography. Dose–volume parameters for the PTV and the organs at risk (OARs), total number of monitor units (MUs) and treatment time were evaluated. Acute toxicity was assessed using the Common Terminology Criteria for Adverse Events, version 4.0. All dosimetric parameters met the present plan acceptance criteria. Mean MU and treatment time were 471 and 146 s for double-arc VMAT, respectively, and were 520 and 76 s for single-arc VMAT, respectively. No Grade 3 or higher acute toxicity was reported. Acute Grade 2 proctitis, diarrhea, and genitourinary toxicity occurred in 12 patients (12%), 6 patients (6%) and 13 patients (13%), respectively. The present study demonstrated that VMAT for WPRT in prostate cancer results in favorable PTV coverage and OAR sparing with short treatment time and an acceptable rate of acute toxicity. These findings support the use of VMAT for delivering WPRT to high-risk prostate cancer patients.     

Hemithoracic intensity-modulated radiotherapy using helical tomotherapy for patients after extrapleural pneumonectomy for malignant pleural mesothelioma

Postoperative hemithoracic irradiation is regarded as an important part of the curative treatment for resectable malignant pleural mesothelioma (MPM). Because the clinical target volume in postoperative MPM is irregular and surrounded by dose-limiting critical structures, intensity-modulated radiation therapy (IMRT) is thought to be suitable. However, postoperative hemithoracic IMRT remains experimental due to a high incidence of fatal pneumonitis. Therefore, a Phase I dose escalation study for hemithoracic IMRT using helical tomotherapy was planned, and the results of the first three patients are herein reported because this technique may provide benefits to such patients. For 3 patients with postoperative MPM, who were treated by extrapleural pneumonectomy (EPP), a radiation dose of 45.0 Gy in 25 fractions was given to cover 95% of the PTV. The lung V5s of the three patients were 14.3%, 10.0%, and 31.3%, respectively. The V5s of the present plans was smaller than that of the recent IMRT planning studies. The lung V20s of these patients were 2.4%, 2.2%, and 4.3%, respectively. Their MLDs were 4.3 Gy, 3.4 Gy, and 5.8 Gy, respectively. The follow-up periods of the patients were 26, 14 and 9 months from initiation of IMRT, respectively. All patients were alive, although local and contralateral recurrences had developed in 1 patient. Only 1 patient had Grade 2 acute esophagitis and nausea. There was no treatment-related pneumonitis. Hemithoracic IMRT using helical tomotherapy may play a crucial role in adjuvant treatment for MPM after EPP.     

奥沙利铂联合卡培他滨治疗晚期直肠癌的临床观察

目的：探讨及评价奥沙利铂（L-OHP）联合卡培他滨（Capecitabine,希罗达）治疗晚期直肠癌的客观疗效及毒性反应。方法：回顾性分析23例经病理证实均为晚期直肠癌患者的临床资料。具体用法：奥沙利铂130mg/m2,静脉滴注2h,d1;卡培他滨1000mg/m2,口服,2次/d,d1～14。21d为1周期,化疗2个或2个周期以上评价疗效及其毒性反应。结果：23例患者均可评价疗效,CR4例,PR11例,SD5例,PD3例,有效率（RR）为65.21%（15/23）;肿瘤中位进展时间为8.2个月。毒性反应主要为骨髓抑制、神经毒性及腹泻。结论：奥沙利铂联合卡培他滨治疗晚期直肠癌有相对较好疗效,毒副反应可以耐受,用药安全,值得临床进一步推广。     

The effects of two HDR brachytherapy schedules in locally advanced cervical cancer treated with concurrent chemoradiation: a study from Chiang Mai, Thailand

Efficacy of different schedules of HDR brachytherapy in concurrent chemoradiotherapy was evaluated. The study compared the effectiveness of the two HDR brachytherapy schedules which have the same Biological Effective Dose (BED) in locally advanced cervical carcinoma that was treated with concurrent chemoradiotherapy. Included in the study were 377 randomly selected patients with advanced carcinoma of the cervix uteri who were treated during the period 2004-2006. Patients were divided into Group I: 7.2 Gy × 3 fractions and Group II: 6 Gy × 4 fractions. With a median follow-up time of 35 months, local control, disease-free survival and overall survival rates were 80.8%, 63.4%, 98.8% in group I and 86.7%, 63.8%, 97.3% in group II, respectively. There was no statistical significance in terms of local control, disease-free survival, overall survival and complication rates between the two treatment schedules which could be observed. Seven patients in group I developed acute grade 2-4 GI toxicities and two patients in group II. In GU toxicities, there were three patients in group I and three patients in group II who developed grade 2-4 toxicities. In late toxicity, no patient developed grade 3-4 GU toxicities in group I while two patients developed grade 3-4 GU toxicities in group II. In GI toxicities, there were five and six patients in group I and group II, respectively, who developed grade 3-4 severity. Both HDR schedules seem to be safe and effective for the treatment of locally advanced cervical cancer.     

Soy Isoflavones in Conjunction With Radiation Therapy in Patients With Prostate Cancer

Soy isoflavones sensitize prostate cancer cells to radiation therapy by inhibiting cell survival pathways activated by radiation. At the same time, soy isoflavones have significant antioxidant and anti-inflammatory activity, which may help prevent the side effects of radiation. Therefore, we hypothesized that soy isoflavones could be useful when given in conjunction with curative radiation therapy in patients with localized prostate cancer. In addition to enhancing the efficacy of radiation therapy, soy isoflavones could prevent the adverse effects of radiation. We conducted a pilot study to investigate the effects of soy isoflavone supplementation on acute and subacute toxicity (≤6 mo) of external beam radiation therapy in patients with localized prostate cancer. Forty-two patients with prostate cancer were randomly assigned to receive 200 mg soy isoflavone (Group 1) or placebo (Group 2) daily for 6 mo beginning with the first day of radiation therapy, which was administered in 1.8 to 2.5 Gy fractions for a total of 73.8 to 77.5 Gy. Adverse effects of radiation therapy on bladder, bowel, and sexual function were assessed by a self-administered quality of life questionnaire at 3 and 6 mo. Only 26 and 27 patients returned completed questionnaires at 3 and 6 mo, respectively. At each time point, urinary, bowel, and sexual adverse symptoms induced by radiation therapy were decreased in the soy isoflavone group compared to placebo group. At 3 mo, soy-treated patients had less urinary incontinence, less urgency, and better erectile function as compared to the placebo group. At 6 mo, the symptoms in soy-treated patients were further improved as compared to the placebo group. These patients had less dripping/leakage of urine (7.7% in Group 1 vs. 28.4% in Group 2), less rectal cramping/diarrhea (7.7% vs. 21.4%), and less pain with bowel movements (0% vs. 14.8%) than placebo-treated patients. There was also a higher overall ability to have erections (77% vs. 57.1%). The results suggest that soy isoflavones taken in conjunction with radiation therapy could reduce the urinary, intestinal, and sexual adverse effects in patients with prostate cancer.     

Dose-volume analysis for respiratory toxicity in intrathoracic esophageal cancer patients treated with definitive chemoradiotherapy using extended fields

Purpose: We evaluated the relationship between dosimetric parameters (DPs) and the incidence of radiation pneumonitis (RP) and investigated the feasibility of a proposed treatment planning technique with the potential of reducing RP in esophageal cancer patients treated with definitive chemoradiotherapy using extended fields. Patients and Methods: A total of 149 patients with locally advanced esophageal cancer were prospectively enrolled for extended-field radiotherapy (EFRT) to three-field regional lymphatics between September 2004 and June 2009. We retrospectively reviewed 86 consecutive patients who were treated with a total dose of 50.4 Gy (plus an optional 9 Gy boost) and were available for dose-volume analysis. Lung DPs of patients in the Grade 0–1 RP (RP_G≤1) group and the Grade 2–5 RP (RP_G≥2) group were compared. We compared the proposed plan with the conventional plan to 50.4 Gy on DPs for each case. Results: Of these 86 patients, 10 (12%) developed RP_G≥2 (Grade 2, n = 2 patients; Grade 3, n = 3; Grade 4, n = 3; Grade 5, n = 2). The patients in the RP_G≤1 group showed significantly lower (P < 0.05) V5 and V10 values for the whole lung compared with those in the RP_G≥2 group. There were two advantages gained from the proposed plan for V5 (<55%) and V10 (< 37%) values and the conformity of the PTV. Conclusion: The increase in the volume of the lung exposed to low doses of EFRT was found to be associated with the incidence of RP. Our proposed plan is likely to reduce the incidence of RP.     

Survey of malignant pleural mesothelioma treatment in Japan: Patterns of practice and clinical outcomes in tomotherapy facilities

We conducted a nationwide survey of tomotherapy for malignant pleural mesothelioma (MPM) in Japan. Fifty-six facilities were surveyed and data on 31 patients treated curatively between 2008 and 2017 were collected from 14 facilities. Twenty patients received hemithorax irradiation after extrapleural pneumonectomy (EPP) (first group). Five patients received irradiation without EPP (second group), while six received salvage radiotherapy for local recurrence (salvage group). Among the seven patients not undergoing EPP, five (four in the second group and one in the salvage group) were treated with lung sparing pleural irradiation (LSPI) and two with irradiation to visible tumors. Two-year overall survival (OS) rates in the first and second groups were 33% and 60%, respectively (median, 13 vs 30 months, P = 0.82). In the first and second groups, 2-year local control (LC) rates were 53 and 67%, respectively (P = 0.54) and 2-year progression-free survival (PFS) rates were 16% and 60%, respectively (P = 0.07). Distant metastases occurred in 15 patients in the first group and three in the second group. In the salvage group, the median OS was 18 months. Recurrence was observed in the irradiated volume in four patients. The contralateral lung dose was higher in LSPI than in hemithorax irradiation plans (mean, 11.0 ± 2.2 vs 6.1 ± 3.1 Gy, P = 0.002). Grade 3 or 5 lung toxicity was observed in two patients receiving EPP and hemithorax irradiation, but not in those undergoing LSPI. In conclusion, outcomes of EPP and hemithorax irradiation were not satisfactory, whereas LSPI appeared promising and encouraging.