98例老年前列腺癌根治术后调强技术放疗结果分析

目的 回顾分析老年前列腺癌患者根治术后接受调强技术放疗疗效和不良反应。 方法 2007-2017年收治 98例接受术后放疗的前列腺癌患者,中位年龄 68岁。全组患者中低危 10例、中危 21例、高危 67例。2例患者存在寡转移(均为骨盆骨转移),64例患者联合了内分泌治疗。全组患者中 43例接受辅助放疗,55例接受挽救放疗。放疗均采用了调强技术(55例调强放疗、43例容积调强弧形治疗),前列腺瘤床中位剂量72 Gy。共 29例接受了盆腔淋巴结区域照射,中位放疗剂量50 Gy。 结果 中位随访40个月,全组 5年总生存率、无生化复发生存率、局部控制率分别为90%、76%、100%。辅助放疗和挽救放疗的总生存率、无生化复发生存率、局部控制率均相近[89%和91%(P=0.94)、76%和71%(P=0.79)、100%和100%(P=0.32)]。不良反应方面 1-2级晚期直肠反应发生率为24.1%,1-2级晚期膀胱反应发生率为29.9%,3级为3.4%。 结论 前列腺癌根治术后采用调强技术放疗可以获得很好的疗效,晚期不良反应轻微。     

巨块型宫颈癌肿瘤中心前程同步加量调强放疗止血效果的观察

目的 探讨肿瘤中心前程同步加量调强放疗治疗巨块型宫颈癌大出血的有效性和安全性。方法 21例伴有阴道大出血的巨块型宫颈癌患者,前程(前3次)给予肿瘤中心(宫颈大肿块边界内收2 cm的范围)同步加量放疗15 Gy分3次后给予常规分割剂量(2 Gy/次),肿瘤周边和盆腔全程采用常规分割照射剂量46 Gy分23次。同步化疗采用顺铂25 mg/m²每周方案。外照射结束后给予腔内放疗20 Gy/4次。结果 首程大剂量放疗后24 h内阴道出血量较前减少50%,1周内阴道出血渐止,止血率100%。结论 采用肿瘤中心同步加量调强放疗是巨块型宫颈癌阴道大出血的有效治疗措施。     

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。     

局限期SCLC超分割或大分割放疗同步化疗预后比较

目的 比较超分割或大分割放疗同步化疗对局限期SCLC的生存影响。方法 超分割和大分割组分别入组患者92、96例。超分割组采用45 Gy分30次,2 次/d。大分割组采用55 Gy分22次,1 次/d。采用Kaplan-Meier法计算生存率,Cox模型多因素预后分析。结果 超分割和大分割组患者1、2、5年PFS率分别为82%、61%、59%和85%、69%、69%(P=0.27),OS率分别为85%、41%、27%和77%、34%、27%(P=0.37)。多因素分析显示化疗开始到放疗开始时间≤43 d是PFS的有利因素(P=0.005),化疗开始到放疗结束时间≤63 d、PCI是OS有利因素(P=0.044、0.000)。超分割组和大分割组2、3级急性放射性食管炎发生率分别为28%、9%和16%、2%(P=0.009)。结论 采用加速超分割或大分割方案联合同步化疗的PFS及OS均显著提高。控制化疗开始至放疗开始、结束时间≤43 d、≤63 d有利于提高PFS和OS。但2、3级急性放射性食管炎的发生率超分割组显著高于大分割组。     

胸部3DCRT在广泛期SCLC中的应用研究

目的 评价胸部3DCRT在广泛期SCLC中的价值。方法 选择2004—2009年间收治的171例广泛期SCLC患者纳入研究,其中86例接受胸部3DCRT和全身化疗,85例只接受全身化疗。放疗采用超分割(1.5 Gy/次,2 次/d)或常规分割(2.0 Gy/次,1 次/d)方式,总量40~62 Gy。化疗方案为铂类联合依托泊甙。生存计算采用Kaplan-Meier法并Logrank检验和单因素预后分析,Cox模型多因素预后分析。结果 随访率为100%。全组中位OS期、2年OS率、5年OS率全组分别为15个月、31.5%、2.4%,放疗组的分别为18个月、35.3%、2.4%,化疗组的分别为12个月、14.5%、2.4%(P=0.023)。全组中位PFS期、1年PFS率、2年PFS率全组分别为8个月、27.5%、2.4%,放疗组的分别为9个月、35.4%、6.0%,化疗组的分别为6个月、20.5%、6.0%(P=0.004)。放疗组中超分割总量45 Gy的22例患者中位PFS期11个月,常规分割总量60 Gy的26例患者中位PFS期9个月(P=0.037)。多因素分析显示3DCRT、4周期以上化疗是预后有利因素(P=0.008、0.001)。结论 胸部放疗能改善广泛期SCLC患者OS和PFS,总量45 Gy超分割放疗较佳。胸部放疗和4周期以上化疗对OS是独立的预后有利因素。     

前列腺癌术后不同分割模式放射治疗急性不良反应初步研究

目的 初步比较前列腺癌术后不同分割模式放疗不良反应。方法 收集我院2011-2017年间接受前列腺癌术后中等分割(62.75 Gy分25次,2.51 Gy/次)和术后常规分割(72 Gy分36次,2 Gy/次)放疗患者资料。所有患者均接受了调强放射治疗(IMRT),每日图像引导放射治疗(IGRT)。采用倾向评分匹配法(PSM)将两组分别匹配35例,匹配因素包括年龄、照射范围、内分泌治疗、手术—放疗间隔时间、以及合并症(糖尿病、高血压)。不良反应评价采用北美放射肿瘤协作组(RTOG)急性不良反应评价标准。差异行Fisher′s精确概率法检验。结果 113例患者纳入分析,其中中等分割组41例,常规分割组72例。中位随访时间分别为5.6、45.0个月。中等分割与常规分割组2级急性胃肠、泌尿不良反应分别为7%与7%(P=1.000)、15%与17%(P=0.847)。PSM匹配后两组2级急性胃肠、泌尿不良反应分别为9%与11%(P=0.814)、14%与11%(P=0.670)。无≥3级急性胃肠、泌尿不良反应。结论 初步结果显示前列腺癌术后中等分割与常规分割相比未增加患者急性胃肠、泌尿不良反应风险。     

乳腺癌改良根治术后内乳淋巴结放疗患者VMAT与IMRT计划剂量学比较

目的 探讨容积调强弧形治疗(VMAT)和固定野动态调强放疗(IMRT)在左侧乳腺癌改良根治术后需辅助放疗并内乳淋巴结照射患者的剂量学差异。方法 对20例左侧乳腺癌患者制定VMAT和IMRT两种放疗计划。通过剂量体积直方图计算靶区和危及器官剂量学参数。对分类变量行χ²或Fisher′s精确概率法检验,连续变量根据正态性采用配对t检验或秩和检验。结果 IMRT靶区均匀性指数比VMAT高(P<0.05)。VMAT治疗时间较IMRT更短(P<0.01)。VMAT患侧肺V20Gy、V30Gy优于IMRT (P<0.05)。VMAT在冠脉左前降支Dmean、Dmax和心脏V30Gy、V40Gy、Dmean、Dmax优于IMRT (P<0.01)。食管DmeanVMAT优于IMRT (P<0.05),但健侧肺V5Gy、V10Gy和食管DmaxIMRT优于VMAT (P<0.05)。结论 VMAT可以显著减少心脏、健侧肺、脊髓、食管照射剂量,缩短治疗时间。对于左侧乳腺癌根治术后需辅助放疗并照射内乳淋巴结的患者,VMAT技术比IMRT技术可以更好保护正常组织。     

淋巴结阳性鼻咽癌患者与IMRT后发生远处转移相关性研究

目的 评价颈部转移性淋巴结与鼻咽癌IMRT后发生远处转移之间关系。方法 回顾分析2010—2012年接受IMRT的474例初治无远处转移鼻咽癌患者资料,采用Kaplan-Meier法计算各种生存率并Logrank检验和单因素预后分析,采用进入法进行Cox模型多因素分析。结果 474例患者中400例发生颈部淋巴结转移,122例经IMRT后存在颈部淋巴结残留。4年累计远处转移率13.7%(65/474),4年OS、DFS、LRFS、DMFS分别为82.9%、81.4%、93.5%、86.3%。单因素及多因素分析显示治疗方式、下颈Ⅳ/Ⅴb/Ⅴc区淋巴结转移、颈部转移淋巴结最大直径、残留淋巴结大小、淋巴结消退时间是DMFS的影响因素(P均<0.05)。结论 放化疗能降低鼻咽癌IMRT后远处转移发生率。颈部淋巴结越大,越容易发生残留,残留淋巴结越大,发生远处转移风险越高。颈部大淋巴结(≥6 cm)、残留淋巴结>1 cm及在放疗3个月后仍有淋巴结残留为鼻咽癌IMRT后DMFS的不利预后因素,需探讨更合理的干预治疗方式。     

放射治疗对转移性鼻咽癌生存的影响——基于SEER数据库的回顾性研究

目的 探讨放疗对转移性鼻咽癌(NPC)患者生存的影响及其相关预后因素分析。方法 利用SEER数据库搜索并筛选2010-2015年初诊为转移性NPC患者329例,回顾分析329例患者的病历资料(199例接受放疗,130例未接受放疗)。采用Kaplan-Meier曲线计算总生存(OS)及疾病特异性生存(DSS),采用Logrank检验及Cox回归分析评估不同临床病理因素对转移性NPC患者预后影响。结果 中位随访时间为12个月,3、5年OS率分别为27.4%、19.7%,中位OS期17.9个月。单因素分析结果显示,年龄<50岁、男性、病理未分化型、T3或T4分期、区域淋巴结阳性、脑或肝转移、转移脏器个数1~2个的患者放疗3年后OS及DSS获益。采用倾向得分匹配后单因素及多因素回归分析结果显示,放疗是转移性NPC的独立预后影响因素(OS,P=0.004;DSS,P=0.014)。多因素回归分析结果还显示,60~69岁(OS,P=0.033;DSS,P=0.045)、角化性鳞状细胞癌(OS,P<0.05;DSS,P<0.050)、T4期(OS,P=0.002;DSS,P=0.024)、1~2个(OS,P=0.039;DSS,P=0.058)及3~4个(OS,P=0.003;DSS,P=0.005)脏器转移、未接受化疗(OS,P=0.000;DSS,P=0.000)的患者预后差,而性别、人种、分化程度对OS及DSS无影响。结论 放疗可显著改善转移性NPC患者的OS及DSS。放疗在转移性NPC治疗中的作用机制还需前瞻性随机对照研究进一步明确。     

食管鳞癌SIB-IMRT疗效及预后因素分析

目的 观察食管鳞癌患者同期推量调强放疗(SIB-IMRT)的疗效并对其相关预后因素进行分析。方法 2009—2015年间101例食管鳞癌患者接受SIB-IMRT,PTV处方剂量5040 cGy分28次(180 cGy/次),PGTV 6020 cGy分28次(215 cGy/次)或6160 cGy分28次(220 cGy/次),1 次/d,5 次/周,全程放疗时间为5.5周。观察其不良反应、治疗失败方式及LC和OS率。结果 1、3、5年样本数分别为101、84、45例。1、3、5年LC率分别为81.6%、70.4%、68.4%,OS率分别为72.3%、49.4%、45.2%,中位生存期36个月。单因素和多因素分析均显示临床分期(Ⅰ/Ⅱ/Ⅲ期)、近期疗效(完全缓解/部分缓解/无缓解)为影响OS的因素(P=0.016、0.000、0.005、0.000)。单次分割215 cGy和220 cGy组LC和OS相近(P=0.283、0.951)。全组1、2、3级急性放射性肺炎发生率分别为10.9%、2.0%、2.0%,1、2、3级急性放射性食管炎发生率分别为63.4%、10.9%、4.0%,无一发生急性食管穿孔和出血。5例患者出现晚期放射性肺炎(2例死亡),1例晚期食管狭窄,2例食管穿孔并出血,2例单纯食管出血。220 cGy组急性放射性肺炎、上消化道反应发生率高于215 cGy组(P=0.062、0.024)。肿瘤局部未控和复发占总治疗失败的62.5%。结论 食管癌SIB-IMRT不良反应可耐受,长期疗效较佳,单次分割220 cGy较215 cGy的LC和OS未提高且增加了不良反应。临床分期、近期疗效为影响生存的预后因素。     

Hypofractionated accelerated radiotherapy using concomitant intensity-modulated radiotherapy boost technique for localized high-risk prostate cancer: acute toxicity results

PURPOSE: To evaluate the acute toxicities of hypofractionated accelerated radiotherapy (RT) using a concomitant intensity-modulated RT boost in conjunction with elective pelvic nodal irradiation for high-risk prostate cancer. METHODS AND MATERIALS: This report focused on 66 patients entered into this prospective Phase I study. The eligible patients had clinically localized prostate cancer with at least one of the following high-risk features (Stage T3, Gleason score >/=8, or prostate-specific antigen level >20 ng/mL). Patients were treated with 45 Gy in 25 fractions to the pelvic lymph nodes using a conventional four-field technique. A concomitant intensity-modulated radiotherapy boost of 22.5 Gy in 25 fractions was delivered to the prostate. Thus, the prostate received 67.5 Gy in 25 fractions within 5 weeks. Next, the patients underwent 3 years of adjuvant androgen ablative therapy. Acute toxicities were assessed using the Common Terminology Criteria for Adverse Events, version 3.0, weekly during treatment and at 3 months after RT. RESULTS: The median patient age was 71 years. The median pretreatment prostate-specific antigen level and Gleason score was 18.7 ng/L and 8, respectively. Grade 1-2 genitourinary and gastrointestinal toxicities were common during RT but most had settled at 3 months after treatment. Only 5 patients had acute Grade 3 genitourinary toxicity, in the form of urinary incontinence (n = 1), urinary frequency/urgency (n = 3), and urinary retention (n = 1). None of the patients developed Grade 3 or greater gastrointestinal or Grade 4 or greater genitourinary toxicity. CONCLUSION: The results of the present study have indicated that hypofractionated accelerated RT with a concomitant intensity-modulated RT boost and pelvic nodal irradiation is feasible with acceptable acute toxicity.     

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。     

Long-term use of combined radiation therapy and hormonal therapy in the management of stage D1 prostate cancer

PURPOSE: To determine tumor response, patterns of relapse, and prognostic indicators in patients followed long-term after combined hormonal radiation therapy of adenocarcinoma of the prostate in men with tumor metastatic to pelvic lymph nodes. METHODS AND MATERIALS: Seventy-nine patients with adenocarcinoma of the prostate with pathologically confirmed pelvic lymph node metastases were treated with combined radiation therapy and hormonal therapy. Of these, 55 patients (70%) had T3 disease, with the remainder having earlier-stage disease; 45 (57%) patients had N2 disease (Whitmore-Jewett staging). No distant metastases were detected at initial staging, and no patient had radiographic or pathologic involvement of the para-aortic nodes. Pelvic lymph nodes were irradiated to a dose 45-54 Gy, and the prostate was irradiated to a dose 65-71.8 Gy. Hormonal therapy began up to 2 months before radiation and continued indefinitely. Patients were allowed to select their hormonal therapy and could choose diethylstilbestrol (DES) (2 patients), orchiectomy (21 patients), luteinizing hormone-releasing hormone agonist (12 patients), or combined androgen blockade (44 patients). Prognostic factors examined included microscopic vs. measurable lymph node involvement, one-sided vs. two-sided disease, T stage, pretreatment PSA, method of androgen blockade, and Gleason score. Log-rank analysis was used to determine statistical significance with respect to overall survival, disease-free survival, clinical freedom from progression, and biochemical freedom from progression; Cox multivariate analysis was employed to determine potential confounders. RESULTS: Median follow-up was 6.7 years. There were 25 recurrences among the 79 patients, including 7 biochemical recurrences without clinical evidence of disease, three local recurrences in the prostate, and distant metastases in 14 patients; 2 patients were deceased, with cause of death listed as prostate cancer, though the location of recurrence was unknown. Patients with biochemical failure before 5 years were more likely to fail distantly, 16% vs. 4% (p < 0.001). Overall actuarial survival at 5, 8, and 12 years was 86%, 72%, and 53%, respectively, whereas actuarial disease-free survival was 90%, 87%, and 81%. Ten patients died of intercurrent disease; these included 4 patients who died of a separate (nonpelvic) malignancy of nonadenocarcinomatous histology with no elevation in PSA. When the potential prognostic variables were examined, a trend toward increased biochemical recurrence in patients with Gleason score >or=8 was observed; this became statistically significant when the 4 patients with known residual lymph node disease after biopsy were excluded (p < 0.03). Gleason score remained the only significant indicator on multivariate analysis. A single long-term toxic event, recto-ureteral fistula, was observed. CONCLUSION: Combined hormonal and radiation therapy continues to represent an effective treatment option for patients with adenocarcinoma of the prostate with metastasis confined to pelvic lymph nodes. All patient groups seem to have a better disease-free survival than that reported previously in single-modality hormone or radiation treatment series. There is a suggestion that patients with lower Gleason score have a lower risk for recurrence. Combined modality therapy may also extend disease-free survival and allow patients to maintain independent function.     

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.     

Phase I/II trial evaluating combined radiotherapy and in situ gene therapy with or without hormonal therapy in the treatment of prostate cancer--a preliminary report

PURPOSE: To report the preliminary results of a Phase I/II study combining radiotherapy and in situ gene therapy (adenovirus/herpes simplex virus thymidine kinase gene/valacyclovir) with or without hormonal therapy in the treatment of prostate cancer. METHODS AND MATERIALS: Arm A: low-risk patients (T1-T2a, Gleason score <7, pretreatment PSA <10) were treated with combined radio-gene therapy. A mean dose of 76 Gy was delivered to the prostate with intensity-modulated radiotherapy. Arm B: high-risk patients (T2b-T3, Gleason score >or=7, pretreatment PSA >or=10) were treated with combined radio-gene therapy and hormonal therapy. Hormonal therapy was comprised of a 4-month leuprolide injection and 2-week use of flutamide. Arm C: Stage D1 (positive pelvic lymph node) patients received the same regimen as Arm B, with the additional 45 Gy to the pelvic lymphatics. Treatment-related toxicity was assessed using Cancer Therapy Evaluation Program common toxicity score and Radiation Therapy Oncology Group (RTOG) toxicity score. RESULTS: Thirty patients (13 in Arm A, 14 in Arm B, and 3 in Arm C) completed the trial. Median follow-up was 5.5 months. Eleven patients (37%) developed flu-like symptoms (Cancer Therapy Evaluation Program Grade 1) of fatigue and chills/rigors after gene therapy injection but recovered within 24 h. Four patients (13%) and 2 patients (7%) developed Grade 1 and 2 fever, respectively. There was no patient with weight loss. One patient in Arm B developed Grade 3 elevation in liver enzyme, whereas 11 and 2 patients developed Grade 1 and 2 abnormal liver function tests. There was no Grade 2 or above hematologic toxicity. Three patients had transient rise in creatinine. There was no RTOG Grade 3 or above lower gastrointestinal toxicity. Toxicity levels were as follows: 4 patients (13%), Grade 2; 6 patients (20%), Grade 1; and 20 patients (67%), no toxicity. There was 1 patient with RTOG Grade 3 genitourinary toxicity, 12 patients (40%) with Grade 2, 8 patients (27%) with Grade 1, and 9 patients (30%) with no toxicity. No patient dropped out from the trial or had to withhold treatment because of severe toxicity. CONCLUSIONS: This is the first trial of its kind in the field of prostate cancer that aims to expand the therapeutic index of radiotherapy by combining in situ gene therapy. Initial experience has demonstrated the safety of this approach. There is no added toxicity to each therapy used alone. Long-term follow-up and larger cohort studies are warranted to evaluate long-term toxicity and efficacy.     

66例局限期中危前列腺癌IMRT疗效分析

目的 分析局限期中危前列腺癌IMRT疗效和不良反应,分析PSA变化水平和意义。方法 回顾分析2007—2018年间经本院IMRT局限期中危前列腺癌66例资料。60例放疗前接受内分泌治疗,6例照射野包括盆腔淋巴引流区,47例采用IGRT技术。前列腺精囊腺中位剂量78 Gy,盆腔淋巴引流区中位剂量48 Gy。采用Kaplan-Meier法计算生存率。结果 中位年龄77岁,中位随访时间71.3个月。5年样本量47例。3、5年OS率分别为98%、90%,CSS率分别为100%、93%,BRFS率分别为97%、86%。PSA降至最低点的平均时间为5.83个月。IMRT后PSA最低点中位数为0.06 ng/ml。1、2级早期泌尿系统不良反应发生率分别为38%、6%,1、2级早期直肠不良反应发生率分别为21%、3%,1、2级晚期泌尿系统不良反应发生率分别为9%、2%,1级晚期直肠不良反应发生率为5%。结论 局限期中危前列腺癌IMRT疗效好,早期、晚期不良反应小,IMRT后PSA监测利于判断肿瘤预后。     

The protective effect of recombinant human keratinocyte growth factor on radiation-induced pulmonary toxicity in rats

PURPOSE: There is an evolving role for combining radiotherapy (RT) with gene therapy in the management of prostate cancer. However, the clinical results of this combined approach are much needed. The preliminary results addressing the safety of this Phase I-II study combining RT and gene therapy (adenovirus/herpes simplex virus-thymidine kinase gene/valacyclovir with or without hormonal therapy) in the treatment of prostate cancer have been previously reported. We now report the prostate-specific antigen (PSA) response and biopsy data. METHODS AND MATERIALS: This trial was composed of three separate arms. Arm A consisted of low-risk patients (Stage T1-T2a, Gleason score <7, pretreatment PSA <10 ng/mL) treated with combined RT-gene therapy. A mean dose of 76 Gy was delivered to the prostate with intensity-modulated RT. They also received adenovirus/herpes simplex virus-thymidine kinase/valacyclovir gene therapy. Arm B consisted of high-risk patients (Stage T2b-T3, Gleason score >6, pretreatment PSA level >10 ng/mL) treated with combined RT-gene therapy and hormonal therapy (luteinizing hormone-releasing hormone agonist [30-mg Lupron, 4-month depot] and an antiandrogen [flutamide, 250 mg t.i.d. for 14 days]). Arm C consisted of patients with Stage D1 (positive pelvic lymph nodes) who received the same regimen as Arm B with the addition of 45 Gy to the pelvic lymphatics. PSA determination and biopsy were performed before, during, and after treatment. The American Society for Therapeutic Radiology and Oncology consensus definition (three consecutive rises in PSA level) was used to denote PSA failure. RESULTS: Fifty-nine patients (29 in Arm A, 26 in Arm B, and 4 in Arm C) completed the trial. The median age was 68 years (range, 39-85 years). The median follow-up for the entire group was 13.5 months (range, 1.4-27.8 months). Only Arm A patients were observed to have an increase in PSA on Day 14. The PSA then declined appropriately. All patients in Arm A (median follow-up, 13.4 months) and Arm B (median follow-up, 13.9 months) had biochemical control at last follow-up. Three patients in Arm C (with pretreatment PSA of 335, 19.6, and 2.5 ng/mL and a combined Gleason score of 8, 9, and 9 involving all biopsy cores) had biochemical failure at 3, 3, and 7.7 months. Two patients had distant failure in bone and 1 patient in the para-aortic lymph nodes outside the RT portal. Six to twelve prostate biopsies performed in these 3 patients revealed no evidence of residual carcinoma. In Arm A, biopsy showed no evidence of carcinoma in 66.7% (18 of 27), 92.3% (24 of 26), 91.7% (11 of 12), 100% (8 of 8), and 100% (6 of 6) at 6 weeks, 4 months, 12 months, 18 months, and 24 months after treatment, respectively. In Arm B, no evidence of carcinoma on biopsy was noted in 96% (24 of 25), 90.5% (19 of 21), 100% (14 of 14), 100% (7 of 7), and 100% (2 of 2), respectively, in the same interval after treatment. CONCLUSION: This is the first reported trial of its kind in the field of prostate cancer that aims to expand the therapeutic index of RT by combining it with in situ gene therapy. The initial transient PSA rise in the Arm A patients may have been a result of local immunologic response or inflammation elicited by in situ gene therapy. Additional investigation to elucidate the mechanisms is needed. Hormonal therapy may have obliterated this rise in Arm B and C patients. The biopsy data were encouraging and appeared to show no evidence of malignancy earlier than historical data. Combined RT, short-course hormonal therapy, and in situ therapy appeared to provide good locoregional control but inadequate systemic control in patients with positive pelvic lymph nodes. Longer term use of hormonal therapy in addition to gene therapy and RT has been adopted for this group of patients to maximize both locoregional and systemic control.     

The evolving role of pelvic radiation therapy

Whole pelvic radiotherapy (WPRT) is controversial in the management of prostate cancer. The estimation of the risk of pelvic lymph node involvement in prostate cancer patients will identify those who will potentially benefit from WPRT. Nomograms and equations based on pretreatment prostate-specific antigen (PSA), Gleason score, and/or clinical stage allow clinicians to quickly estimate nodal risk. Most of the studies analyzing WPRT, including a randomized trial from the Radiation Therapy Oncology Group (RTOG), were conducted in the pre-PSA era and did not necessarily include patients at high risk for nodal involvement. The addition of hormonal therapy to WPRT has been shown in 4 major prospective randomized trials to improve survival for some subsets of patients. The preliminary results of RTOG 94-13 show the superiority of WPRT over prostate-only radiotherapy (PORT) in high-risk prostate cancer patients receiving hormonal therapy. For most other solid tumors, the regional lymph nodes are routinely treated by some modality, so it is not surprising that WPRT might benefit a subset of high-risk patients.