前列腺癌局部调强放疗是否同步盆腔照射不良反应比较

目的 分析前列腺癌调强放疗中盆腔照射与否的肠道和泌尿道急慢性不良反应差别。
方法 2009-2012年局限于盆腔接受根治性调强放疗的前列腺癌83例,其中38例中低危患者前列腺±精囊腺放疗67.5 Gy,45例高危或盆腔淋巴结转移风险预测>15%者前列腺和精囊腺放疗67.5 Gy同步盆腔照射50 Gy。急性不良反应依据不良反应常见术语标准3.0版进行评价,慢性不良反应依据美国肿瘤放疗协会标准评测。
结果 盆腔放疗与无放疗的肠道2、3级急性不良反应分别为27%、0%与5%、3%(P=0.025),晚期不良反应分别为11%、9%与29%、3%(P=0.170);泌尿道2、3级急性不良反应分别为13%、0%与16%、3%(P=0.368),慢性不良反应分别为9%、2%与24%、3%(P=0.066)。
结论 前列腺癌放疗中盆腔放疗增加了肠道急性不良反应,但未增加肠道和泌尿道晚期损伤。     

Moderately Hypofractionated Radiotherapy and Androgen Deprivation Therapy for High-risk Localised Prostate Cancer: Predictors of Long-term Biochemical Control and Toxicity

AimsThere is a paucity of long-term data on outcomes of high-risk prostatic adenocarcinoma after moderately hypofractionated radiotherapy with elective nodal treatment and long-term androgen deprivation therapy (ADT). We report long-term control and toxicity outcomes and analyse the predictors of failure and toxicity.Materials and methodsThe records of 120 consecutive high-risk prostate cancer patients treated in a single institution between February 2012 and December 2016 were retrospectively analysed. A moderately hypofractionted radiotherapy (HypoRT) regimen of 60 Gy in 20 fractions over 4 weeks with simultaneous elective pelvic irradiation to 44 Gy in 20 fractions with intensity-modulated radiotherapy was used, together with long-term ADT with either orchiectomy or medical castration for a total duration of 2–3 years. We analysed biochemical control, metastasis-free survival and late toxicities and their predictive factors using survival analysis.ResultsPatients had locally advanced cancers (cT3 77.5%, median pretreatment prostate-specific antigen 30 ng/ml, Gleason score 8–10 in 45.8%). The median follow-up time was 70 months. The 3- and 5-year probability of freedom from biochemical progression was 93% and 80%, respectively. The 5-year probability of freedom from local relapse/intra-pelvic nodal relapse/distant metastases as the site of first failure was 96%/97%/86%, respectively. Gleason score 8–10 and medical ADT for 2–3 years (as opposed to orchidectomy) were independent risk factors for distant metastases. A total of 18 grade 2 and above late gastrointestinal toxicity events and a total of 23 grade 2 and above late genitourinary toxicity events were documented. Patients who underwent a transurethral resection of prostate prior to radiotherapy had worse urological toxicity.ConclusionsHypoRT with elective nodal treatment results in excellent pelvic control. Distant metastases are the primary mode of failure. Risk of metastases is associated with Gleason score and the duration of ADT. Late urinary toxicities are more common in those with prior transurethral resection of prostate.     

Individualized planning target volumes for intrafraction motion during hypofractionated intensity-modulated radiotherapy boost for prostate cancer

Purpose: The objective of the study was to access toxicities of delivering a hypofractionated intensity-modulated radiotherapy (IMRT) boost with individualized intrafraction planning target volume (PTV) margins and daily online correction for prostate position. Methods and materials: Phase I involved delivering 42 Gy in 21 fractions using three-dimensional conformal radiotherapy, followed by a Phase II IMRT boost of 30 Gy in 10 fractions. Digital fluoroscopy was used to measure respiratory-induced motion of implanted fiducial markers within the prostate. Electronic portal images were taken of fiducial marker positions before and after each fraction of radiotherapy during the first 9 days of treatment to calculate intrafraction motion. A uniform 10-mm PTV margin was used for the first phase of treatment. PTV margins for Phase II were patient-specific and were calculated from the respiratory and intrafraction motion data obtained from Phase I. The IMRT boost was delivered with daily online correction of fiducial marker position. Acute toxicity was measured using National Cancer Institute Common Toxicity Criteria, version 2.0. Results: In 33 patients who had completed treatment, the average PTV margin used during the hypofractionated IMRT boost was 3 mm in the lateral direction, 3 mm in the superior-inferior direction, and 4 mm in the anteroposterior direction. No patients developed acute Grade 3 rectal toxicity. Three patients developed acute Grade 3 urinary frequency and urgency. Conclusions: PTV margins can be reduced significantly with daily online correction of prostate position. Delivering a hypofractionated boost with this high-precision IMRT technique resulted in acceptable acute toxicity.     

Stereotactic body radiotherapy as boost for organ-confined prostate cancer

Stereotactic body radiotherapy (SBRT) boost following external beam radiation therapy (EBRT) for advanced localized prostate cancer may reduce toxicity while escalating the dose. We present preliminary biochemical control and urinary, rectal and sexual toxicities for 73 patients treated with SBRT as a boost to EBRT. Forty-one intermediate- and 32 high-risk localized prostate cancer patients received 45 Gy EBRT with SBRT boost. Twenty-eight patients (38.3%) received a total SBRT boost dose of 18 Gy (3 fractions of 6 Gy), 28 patients (38.3%) received 19.5 Gy (3 fractions of 6.5 Gy), and 17 patients (23.2%) received 21 Gy (3 fractions of 7 Gy). Toxicity was assessed using the Radiation Therapy Oncology Group urinary and rectal toxicity scale. Biochemical failure was assessed using the Phoenix definition. The median follow-up was 33 months (range, 22 - 43 months). Less than 7% Grade II and no higher grade acute toxicities occurred. To date, one Grade III and no Grade IV late toxicities occurred. For the 97% of patients with 24 months minimum follow-up, 71.8% achieved a PSA nadir threshold of 0.5 ng/mL. Three intermediate-risk and seven high-risk biochemical failures occurred; one high-risk patient died of his cancer. Three-year actuarial biochemical control rates were 89.5% and 77.7% for intermediate- and high-risk patients, respectively. SBRT boost for prostate cancer treatment is safe and feasible with minimal acute toxicity. At 33 months late toxicity and biochemical control are promising. Long-term durability of these findings remains to be established.     

前列腺癌大分割调强放疗副反应初步分析

目的 分析前列腺癌大分割照射患者的早期和晚期副反应,初步探讨副反应的影响因素.方法 2006-2008年间37例前列腺痛患者接受大分割调强放疗(IMRT).13例临床靶体积(CTV)包括前列腺±精囊或术后瘤床,24例包括前列腺、精囊(或术后瘤床)和盆腔淋巴引流区.分次照射剂量为2.3～2.8 Gy(2.7 Gy占26例).95%PTV处方剂量前列腺精囊为62.5～75.0 Gy,盆腔为50.0 Gy.结果 全组中位随访时间为14个月.早期胃肠反应发生率0级38%,1级2,4%,2级35%,3级3%;直肠V50>27%与V55>20%的≥1级早期直肠反应发生率不同(P<0.05).早期泌尿系统反应发生率0级30%,1级68%,2级0和3级3%;膀胱V60<10%与V60>10%的≥1级泌尿系统反应发生率也不同(X2=6.02,P=0.038).晚期直肠反应发生率0级70%,1级24%,2级5%,无3、4级反应;直肠V65<10%与V65>10%的≥1级晚期胃肠反应发生率不同(X2=5.58,P=0.020).晚期泌尿系统反应发生率0级38%,1级49%,2级11%,3级3%,无4级反应;膀胱平均剂量>40Gy、V40>32%与V50>29%的≥2级晚期泌尿系统反应发生率均不同.结论 前列腺癌大分割IMRT初步研究结果 显示急件和晚期副反应均在可接受范围内.     

Salvage hypofractionated radiotherapy for biochemically recurrent prostate cancer after radical prostatectomy

PURPOSE: To evaluate whether hypofractionation is well tolerated and to preliminarily assess biochemical control of this regimen in a postprostatectomy, salvage setting. METHODS AND MATERIALS: A retrospective analysis was performed in 50 patients treated between May 2003 and December 2005 with hypofractionated radiotherapy for biochemical recurrence after radical prostatectomy. Radiotherapy was prescribed to the prostatic fossa to 65-70 Gy in 26-28 fractions of 2.5 Gy each, using intensity-modulated radiotherapy with daily image localization. Toxicities were scored using a modified Radiation Therapy Oncology Group scale and the Fox Chase modification of Late Effects Normal Tissue scale. The median follow-up was 18.9 months (range, 5.3-35.9). RESULTS: No Grade 3 or greater acute or late toxicities were observed. Grade 2 toxicities included four acute genitourinary, one acute gastrointestinal, two late genitourinary, and two late gastrointestinal toxicities. Of the 50 patients, 39 demonstrated a continuous biochemical response after salvage therapy, 3 had an initial response before prostate-specific antigen failure, and 7 had prostate-specific antigen progression, 1 of whom died of progressive metastatic disease. Finally, 1 patient discontinued therapy because of the diagnosis of a metachronous pancreatic cancer and died without additional prostate cancer follow-up. All remaining patients were alive at the last follow-up visit. A lower presalvage prostate-specific antigen level was the only significant prognostic factor for improved biochemical control. The estimated actuarial biochemical control rate at 2 years was 72.9%. CONCLUSIONS: The toxicity and early biochemical response rates were consistent with expectations from conventional fractionation. Additional follow-up is required to better document the biochemical control, but these results suggest that hypofractionation is a well-tolerated approach for salvage radiotherapy.     

Significant reduction of acute toxicity following pelvic irradiation with helical tomotherapy in patients with localized prostate cancer.

PURPOSE: To assess and quantify the possible benefit deriving from IMRT with Helical Tomotherapy (HTT) delivery to the pelvic nodal area in patients with prostate cancer in terms of reduction of acute and late toxicities. METHODS AND MATERIALS: Thirty-five patients candidate to radical or postoperative RT on whole pelvis (WPRT) were treated with HTT, while receiving a concomitant boost to the prostate or the prostatic bed (median 74.2 and 72 Gy, respectively) within a moderately hypofractionated (28-33 fractions; median HTT duration 44 days) regimen. Median and mean doses to whole pelvis were 52 and 54 Gy, respectively. One of the major goals of planning optimisation was to minimize the dose received by the intestinal cavity (IC) outside the nodal PTV. RESULTS: HTT resulted to be very efficient in sparing the IC even at dose levels below 30-35 Gy and guaranteed a significant sparing of bladder and rectum even at intermediate-low doses (V20-V40). No acute Grade 3 RTOG toxicity was recorded. Eighteen G1 and two G2 GU acute toxicities, 13 G1 upper GI acute toxicities, 8 G1 and 1 G2 acute proctitis were observed; no patient experienced G2 upper GI toxicity. After a median FU of 11.5 months (>10 in 18 patients) one case of late G3 GU toxicity was reported in one post-prostatectomy treated patient; no G2 late rectal bleeding or other GI toxicity was recorded. CONCLUSIONS: WPRT with HTT resulted in a very low incidence of acute Grade 2 and in the disappearance of acute Grade 3 toxicities.     

Safety and Efficacy of Ultra-hypofractionation in Node-positive Prostate Cancer

AimsThe safety and efficacy of stereotactic body radiotherapy (SBRT) in localised prostate cancer are now established through phase III randomised trials. Its utility in node-positive prostate cancer is restricted due to a lack of controlled studies specifically addressing this subgroup. Herein we report the safety and efficacy of SBRT in this subgroup.Materials and methodsIn total, 60 patients treated with SBRT to prostate and pelvis were analysed. All patients received neoadjuvant androgen deprivation therapy for at least 6 months and long-term adjuvant hormonal therapy (70% medical and 30% surgical). All patients were treated with daily image-guided rotational intensity-modulated radiotherapy. The dose delivered to the prostate and gross node was 35–37.5 Gy and 25 Gy in five fractions to the elective pelvic nodal region on alternate days. Acute and late toxicities were graded as per Radiation Therapy Oncology Group common toxicity criteria.ResultsForty-one (68%) patients had a Gleason score ≥8. The median prostate-specific antigen level at diagnosis was 39 ng/ml. Twenty (33%) patients had common iliac nodal uptake on initial prostate-specific membrane antigen positron emission tomography-computed tomography. After the median follow-up of 30 months, no acute or late Radiation Therapy Oncology Group grade ≥3 gastrointestinal toxicity was noted. Acute grade 2 genitourinary and gastrointestinal toxicities were 8.3% and 11.7%, respectively. Late grade 2 genitourinary and gastrointestinal toxicities were 3.3% and 8.3%, respectively. Late grade 3 genitourinary toxicity was seen in two (3.3%) patients. Three-year overall survival and biochemical failure-free survival was 89% and 77%, respectively.ConclusionSBRT to the prostate and pelvis is safe and efficacious in node-positive prostate cancer even with common iliac nodal involvement (stage M1a).     

Phase II trial of hypofractionated image-guided intensity-modulated radiotherapy for localized prostate adenocarcinoma

PURPOSE: To assess in a prospective trial the feasibility and late toxicity of hypofractionated radiotherapy (RT) for prostate cancer. METHODS AND MATERIALS: Eligible patients had clinical stage T1c-2cNXM0 disease. They received 60 Gy in 20 fractions over 4 weeks with intensity-modulated radiotherapy including daily on-line image guidance with intraprostatic fiducial markers. RESULTS: Between June 2001 and March 2004, 92 patients were treated with hypofractionated RT. The cohort had a median prostate-specific antigen value of 7.06 ng/mL. The majority had Gleason grade 5-6 (38%) or 7 (59%) disease, and 82 patients had T1c-T2a clinical staging. Overall, 29 patients had low-risk, 56 intermediate-risk, and 7 high-risk disease. Severe acute toxicity (Grade 3-4) was rare, occurring in only 1 patient. Median follow-up was 38 months. According to the Phoenix definition for biochemical failure, the rate of biochemical control at 14 months was 97%. According to the previous American Society for Therapeutic Radiology and Oncology definition, biochemical control at 3 years was 76%. The incidence of late toxicity was low, with no severe (Grade > or =3) toxicity at the most recent assessment. CONCLUSIONS: Hypofractionated RT using 60 Gy in 20 fractions over 4 weeks with image guidance is feasible and is associated with low rates of late bladder and rectal toxicity. At early follow-up, biochemical outcome is comparable to that reported for conventionally fractionated controls. The findings are being tested in an ongoing, multicenter, Phase III trial.     

Moderately Hypofractionated Radiotherapy in Node-positive Prostate Cancer

Aims

Node-positive prostate cancer is a unique subgroup, with varied practice on locoregional treatment. Definitive treatment with hypofractionated radiotherapy has not been widely reported. We have routinely used standard regimens of hypofractionated radiotherapy for node-positive disease and report our results of toxicity, biochemical control and survival.

Hypofractionated External Beam Radiotherapy to Boost the Prostate with ≥85 Gy/Equivalent Dose for Patients with Localised Disease at High Risk of Lymph Node Involvement: Feasibility,Tolerance and Outcome

AimsTo evaluate the tolerance and preliminary outcome of prostate cancer patients at high risk of lymph node involvement treated with normofractionated whole pelvic radiotherapy (WPRT) followed by a hypofractionated boost to the prostate with an intensity-modulated radiotherapy (IMRT) technique.Materials and methodsBetween 2004 and 2011, 78 T1-4N0M0 prostate cancer patients at high risk of lymph node involvement (70 patients with a Roach index ≥ 15%; 57 with T-stage ≥ 3a; 40 with Gleason score ≥ 8) underwent WPRT to a median normofractionated dose of 50.4 Gy (range 48.0–50.4 Gy) with conformal three-dimensional techniques for most patients. A 24 Gy boost (4 Gy/six fractions, twice weekly) was delivered to the prostate with IMRT. The total median delivered dose was 74.4 Gy, equivalent to 85.2 Gy in 2 Gy/fractions (α/β = 1.5 Gy). All patients underwent androgen deprivation for a total median time of 10.8 months. The maximum gastrointestinal and genitourinary acute and late toxicity scores were recorded according to the Radiation Therapy Oncology Group scoring system.ResultsAll patients completed treatment as planned. Only 1% of patients presented with grade 3 genitourinary or gastrointestinal acute toxicity and none scored ≥ grade 4. With a median follow-up of 57 months, the 5 year probability of late grade ≥2 genitourinary and gastrointestinal toxicity-free survival was 79.1 ± 4.8% and 84.1 ± 4.5%, respectively. The 5 year biochemical disease-free survival, local relapse-free survival and distant metastasis-free survival were 84.5 ± 4.5%, 96.0 ± 2.8% and 86.4 ± 4.4%, respectively. A pre-radiotherapy prostate-specific antigen ≤0.3 ng/ml was associated with a better 5 year biochemical disease-free survival (P = 0.036) and distant metastasis-free survival (P = 0.049).ConclusionsThe use of a hypofractionated IMRT boost after WPRT may allow a minimally invasive dose escalation to successfully treat patients with non-metastatic prostate cancer at high risk of lymph node involvement. Higher prostate-specific antigen values before radiotherapy may require alternative adjuvant treatments to further optimise the outcome of this high-risk group of patients.     

Early Results of Extreme Hypofractionation Using Stereotactic Body Radiation Therapy for High-risk,Very High-risk and Node-positive Prostate Cancer

Aims

Stereotactic body radiotherapy (SBRT) in low- and intermediate-risk prostate cancer has shown encouraging results. However, its use in high-risk patients is limited due to lack of data regarding adequate radiotherapy dose, need for pelvic nodal treatment and androgen deprivation therapy. Herein we report our experience of SBRT in this subgroup.

Acute toxicity of hypofractionated intensity-modulated radiotherapy for prostate cancer

Background

Dose-escalated hypofractionated radiotherapy (hfrt) using intensity-modulated radiotherapy (imrt), with inclusion of the pelvic lymph nodes (plns), plus androgen suppression therapy (ast) in high-risk prostate cancer patients should improve patient outcomes, but acute toxicity could limit its feasibility.

Methods

Our single-centre phase ii prospective study enrolled 40 high-risk prostate cancer patients. All patients received hfrt using imrt with daily mega-voltage computed tomography imaging guidance, with 95% of planning target volumes (ptv68 and ptv50) receiving 68 Gy and 50 Gy (respectively) in 25 daily fractions. The boost volume was targeted to the involved plns and the prostate (minus the urethra plus 3 mm and minus 3 mm from adjacent rectal wall) and totalled up to 75 Gy in 25 fractions. Acute toxicity scores were recorded weekly during and 3 months after radiotherapy (rt) administration.

Results

For the 37 patients who completed rt and the 3-month follow-up, median age was 65.5 years (range: 50–76 years). Disease was organ-confined (T1c–T2c) in 23 patients (62.1%), and node-positive in 5 patients (13.5%). All patients received long-term ast. Maximum acute genitourinary (gu) and gastrointestinal (gi) toxicity peaked at grade 2 in 6 of 36 evaluated patients (16.6%) and in 4 of 31 evaluated patients (12.9%) respectively. Diarrhea and urinary frequency were the chief complaints. Dose–volume parameters demonstrated no correlation with toxicity. The ptv treatment objectives were met in 36 of the 37 patients.

Conclusions

This hfrt dose-escalation trial in high-risk prostate cancer has demonstrated the feasibility of administering 75 Gy in 25 fractions with minimal acute gi and gu toxicities. Further follow-up will report late toxicities and outcomes.     

Phase I trial of preoperative hypofractionated intensity-modulated radiotherapy with incorporated boost and oral capecitabine in locally advanced rectal cancer

PURPOSE: To determine the safety and efficacy of preoperative hypofractionated radiotherapy using intensity-modulated radiotherapy (IMRT) and an incorporated boost with concurrent capecitabine in patients with locally advanced rectal cancer. METHODS AND MATERIALS: The eligibility criteria included adenocarcinoma of the rectum, T3-T4 and/or N1-N2 disease, performance status 0 or 1, and age > or =18 years. Photon IMRT and an incorporated boost were used to treat the whole pelvis to 45 Gy and the gross tumor volume plus 2 cm to 55 Gy in 25 treatments within 5 weeks. The study was designed to escalate the dose to the gross tumor volume in 5-Gy increments in 3-patient cohorts. Capecitabine was given orally 825 mg/m(2) twice daily for 7 days each week during RT. The primary endpoint was the maximal tolerated radiation dose, and the secondary endpoints were the pathologic response and quality of life. RESULTS: Eight patients completed RT at the initial dose level of 55 Gy. The study was discontinued because of toxicity-six Grade 3 toxicities occurred in 3 (38%) of 8 patients. All patients went on to definitive surgical resection, and no patient had a pathologically complete response. CONCLUSION: This regimen, using hypofractionated RT with an incorporated boost, had unacceptable toxicity despite using standard doses of capecitabine and IMRT. Additional research is needed to determine whether IMRT is able to reduce the side effects during and after pelvic RT with conventional dose fractionation.     

Toxicity after three-dimensional radiotherapy for prostate cancer with RTOG 9406 dose level IV

PURPOSE: This is the first report of the toxicity outcomes using dose level IV (74 Gy) on Radiation Therapy Oncology Group (RTOG) study 9406 for Stage T1-T2 prostate adenocarcinoma. METHODS AND MATERIALS: A total of 262 patients were entered in this cooperative group, Phase I-II, dose-escalation trial of three-dimensional conformal radiotherapy for localized prostate carcinoma treated to a dose of 74 Gy (Level IV); 256 patients were analyzable for toxicity. A minimal dose of 2 Gy/fraction was prescribed to the planning target volume (PTV). Patients were stratified according to the risk of seminal vesicle invasion on the basis of the Gleason score and presenting prostate-specific antigen level. Group 1 patients had clinical Stage T1-T2 tumors with a seminal vesicle invasion risk of <15%. Group 2 patients had clinical Stage T1-T2 tumors with a seminal vesicle invasion risk of >/=15%. Patients in Group 1 were prescribed 74 Gy to a prostate PTV. Patients in Group 2 were prescribed 54 Gy to the prostate and seminal vesicles (PTV1) followed by a boost to the prostate only (PTV2) to 74 Gy. PTV margins between 5 and 10 mm were required. Elective pelvic radiotherapy was not used. The frequency of late effects of Grade 3 or greater was compared with that for a similar group of patients treated in RTOG studies 7506 and 7706, with length of follow-up adjustments made for the interval from therapy completion. A second comparison was made with 206 patients treated to dose level II (73.8 Gy in 1.8-Gy fractions) to see whether the fraction size affected toxicity. RESULTS: The average months at risk for late Grade 3+ toxicity after therapy completion were 28.9 and 23.9 months for Group 1 and 2, respectively. Acute toxicity at dose level IV (74 Gy) was remarkably low, with Grade 3 acute effects reported in only 1% of Group 1 and 3% of Group 2 patients. No Grade 4 or 5 acute toxicities were reported. Late toxicity continued to be low compared with RTOG historical controls. One patient in Group 1 and 4 patients in Group 2 experienced Grade 3 bladder toxicity. Two patients in Group 2 experienced Grade 3 bowel toxicity. No Grade 4 or 5 late effects were reported. The rate of late Grade 2 toxicity (any type) was 23% and 16% in Group 1 and 2, respectively. The observed rate of Grade 3 or greater late effects for Group 1 (1 case) was significantly lower (p <0.0001) than the 18.5 cases that would have been expected from the historical control data. The observed rate for Group 2 (6 cases) was also significantly lower (p = 0.0009) than the 21.3 cases expected. No statistically significant difference was noted in the rate of acute or late toxicity in patients who were treated to 73.8 Gy at 1.8 Gy/fraction or 74 Gy at 2.0 Gy/fraction. Patients treated with the larger 2.0-Gy fractions tended to have more Grade 3 or greater toxicity than patients treated with 1.8-Gy fractions (2% vs. 1%, p = 0.09). The results after the longer follow-up with dose level II suggest these differences may increase with additional follow-up. CONCLUSION: Tolerance to three-dimensional conformal radiotherapy with 74 Gy in 2-Gy fractions remains better than expected compared with historical controls. The magnitude of any effect from fraction size requires additional follow-up.     

Long-Term Outcomes of Dose-Escalated Pelvic Lymph Node Intensity-Modulated Radiation Therapy (IMRT) With a Simultaneous Hypofractionated Boost to the Prostate for Very High-Risk Adenocarcinoma of the Prostate: A Prospective Phase II Clinical Trial

PurposeThere remains limited data as to the feasibility, safety, and efficacy of higher doses of elective radiation therapy to the pelvic lymph nodes in men with high-risk prostate cancer. We conducted a phase II study to evaluate moderate dose escalation to the pelvic lymph nodes using a simultaneous integrated boost to the prostate.Methods and MaterialsPatients were eligible with biopsy-proven adenocarcinoma of the prostate, a calculated lymph node risk of at least 25%, Karnofsky performance scale ≥70, and no evidence of M1 disease. Acute and late toxicity were prospectively collected at each follow-up using Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0). The pelvic lymph nodes were treated to a dose of 56 Gy over 28 fractions with a simultaneous integrated boost to the prostate to a total dose of 70 Gy over 28 fractions using intensity-modulated radiation therapy.ResultsThirty patients were prospectively enrolled from October 2010 to August 2014. Median patient age was 70 years (57-83), pretreatment prostate-specific antigen was 11.5 ng/mL (3.23-111.5), T stage was T2c (T1c-T3b), and Gleason score was 9 (6-9). CTCAE v4.0 rate of any grade 1 or 2 genitourinary and gastrointestinal toxicity were 55% and 44%, respectively, and there was 1 reported acute grade 3 genitourinary and gastrointestinal toxicity, both unrelated to protocol therapy. With a median follow-up of 6.4 years, the biochemical failure free survival rate was 80.2%, and mean biochemical progression free survival was 8.3 years (95% confidence interval [CI], 7.2-9.4). The prostate cancer specific survival was 95.2%, and mean prostate cancer specific survival was 8.7 years (95% CI, 8.0-9.4). Five-year distant metastases free survival was 96%. Medians were not reached.ConclusionsIn this single arm, small, prospective feasibility study, nodal radiation therapy dose escalation was safe, feasible, and seemingly well tolerated. Rates of progression free survival are highly encouraging in this population of predominately National Comprehensive Cancer Network very high-risk patients.     

Phase 1/2 study of hypofractionated intensity-modulated radiation therapy for prostate cancer including simultaneously integrated boost

Purpose

This study evaluates the safety and efficacy of moderately hypofractionated radiation therapy (RT) with simultaneous integrated boost (HSIB) intensity modulated RT (IMRT) that includes coverage of the seminal vesicles (SVs) and pelvic lymph nodes (LNs).

局限期前列腺癌大分割调强放疗临床Ⅱ期研究

目的 观察前列腺癌2.7 Gy 25次大分割调强适形放疗的疗效和不良反应。     

A Phase I/II Study of Stereotactic Hypofractionated Once-weekly Radiation Therapy (SHORT) for Prostate Cancer

AimsStereotactic radiation therapy has been investigated predominantly in patients with low–intermediate-risk disease. We conducted a clinical trial of stereotactic hypofractionated radiation therapy delivered in once-weekly fractions on patients with all-risk non-metastatic disease to test feasibility, acute toxicities and patient-reported outcomes.Materials and methodsIn this phase I/II study, 30 patients with prostatic adenocarcinoma, any Gleason score, T1-4N0 and prostate-specific antigen ≤60 ng/ml were treated with volumetric intensity modulated arc radiation therapy to a dose of 35 Gy in five fractions delivered once weekly. Patients with high-risk disease also received elective nodal irradiation to a dose of 25 Gy in five fractions simultaneously. Androgen deprivation was offered to intermediate- and high-risk patients. The primary outcome was acute toxicity. Secondary outcome measures included biochemical control and late toxicity. Patient-reported outcomes were measured using the International Prostate Symptom Score and European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire (QLQ).ResultsAll 30 patients completed treatment per-protocol. Most patients had T3 (60%) and Gleason 7 (50%) tumours. The median prostate-specific antigen was 17 ng/ml. High-risk disease was present in 20 patients (66.7%). There was a low incidence of acute toxicities (grade 2 + urinary 3.3%, grade 2 rectal 0%). Within the EORTC QLQ framework, only the urinary symptom score showed a clinically meaningful worsening from a mean of 20/100 at baseline to 34/100 at the end of treatment (P < 0.001), but reduced to 24/100 at 6 months (P = 0.08). With a median follow-up of 41.5 months, two patients each reported grade 2 late urinary and rectal toxicity. The 3- and 4-year biochemical control rates were 96.7 and 87.9%, respectively.ConclusionIn a cohort of mainly high-risk cancers, stereotactic once-weekly radiation therapy was easy to implement and well tolerated, with a low incidence of acute and late toxicity and excellent biochemical control.     

Acute toxicity of three-dimensional conformal radiotherapy in prostate cancer patients eligible for implant monotherapy

PURPOSE: To assess the acute toxicity of three-dimensional conformal radiotherapy (3D-CRT) in prostate cancer patients eligible for implant monotherapy. METHODS AND MATERIALS: Between December 1991 and June 1998, 198 prostate cancer patients were treated with 3D-CRT at the University of California Davis Medical Center. Fifty-two of these patients had a prostate-specific antigen (PSA) level /= Grade 3, e.g., hourly nocturia, gross hematuria, diarrhea requiring parenteral support, narcotics for pain control, or catheterization for acute urinary retention, was observed. CONCLUSION: Although relatively high doses of radiation are delivered to prostate cancers with 3D-CRT compared with conventional radiotherapy, 3D-CRT is surprisingly well-tolerated. No patients in the cohort eligible for implant monotherapy experienced acute toxicity >/= Grade 3.