Pelvic insufficiency fracture after pelvic radiotherapy for cervical cancer: analysis of risk factors

PURPOSE: To investigate the incidence, clinical characteristics, and risk factors of pelvic insufficiency fracture (PIF) after pelvic radiotherapy (RT) in cervical cancer. METHODS AND MATERIALS: Medical records and imaging studies, including bone scintigraphy, CT, and MRI of 557 patients with cervical cancer who received whole-pelvic RT between January 1998 and August 2005 were reviewed. RESULTS: Eighty-three patients were diagnosed as having PIF after pelvic RT. The 5-year cumulative incidence of PIF was 19.7%. The most commonly involved site was the sacroiliac joint. Pelvic pain developed in 48 patients (57.8%) at diagnosis. Eleven patients (13.3%) needed admission or narcotics because of severe pain, and others had good relief of symptoms with conservative management. In univariate analysis, age>or=55 years (p<0.001), anteroposterior/posteroanterior parallel opposing technique (p=0.001), curative treatment (p<0.001), and radiation dose>or=50.4 Gy (p=0.005) were the predisposing factors for development of PIF. Concurrent chemotherapy (p=0.78) was not significant. Multivariate analysis showed that age>or=55 years (p<0.001), body weight<55 kg (p=0.02), curative treatment (p=0.03), and radiation dose>or=50.4 Gy (p=0.04) were significant predisposing factors for development of PIF. CONCLUSION: The development of PIF is not rare after pelvic RT. The use of multibeam arrangements to reduce the volume and dose of irradiated pelvic bone can be helpful to minimize the risk of fracture, especially in elderly women with low body weight.     

宫颈癌盆腔淋巴结转移同步推量调强放射治疗的临床研究

目的 子宫颈癌是妇女最常见恶性肿瘤之一,对于中晚期宫颈癌患者放疗是较理想和有效的选择.本研究通过观察不同放疗方法在中晚期宫颈癌合并盆腔淋巴结转移患者的临床应用,比较同步推量调强放射治疗(simultaneous modulated accelerated radiotherapy,SMART)和常规放射治疗(conventional radiotherapy,CRT)对中晚期宫颈癌合并盆腔淋巴结转移患者的剂量学差异和临床效果.方法 选取2009 12-01-2015-06-30临沂市肿瘤医院68例接受SMART和65例行CRT的ⅡB～ⅢB期宫颈癌合并盆腔淋巴结转移患者为研究对象.SMART计划:PTV达到处方剂量50.4～52.2 Gy/28～29次,1.8～1.85 Gy/次,同时给予P-GTV 61.6～67.2 Gy/28～29次,2.2～2.4 Gy/次,计划进行18次给予缩野.CRT计划:5次/周,1.8～1.9 Gy/次,照射剂量达30 Gy后,中间档铅4 cm照射,4次/周,1.8～2.0 Gy/次,至全盆总量达48.2～53.2 Gy;盆腔淋巴结转移侧加量至54.2～58.2 Gy.体外放疗同时给予一体化后装放疗及静脉化疗.比较靶区剂量、危及器官受照射剂量、近期疗效、急慢性不良反应和生存率.结果 两组患者的靶区剂量比较,SMART组中位P-GTV剂量64.7 Gy,CRT组的体外放疗中位剂量(全盆十四野十淋巴结区缩野后)55.4 Gy,两组比较差异有统计学意义,t=33.717,P＜0.001.SMART与拟行CRT计划比较,SMART组小肠(t=12.888,P＜0.001)、结肠(t=11.828,P＜0.001)、膀胱(t=12.135,P＜0.001)、脊髓(t=3.523,P=0.002)、股骨头(t=3.545,P=0.002)受照射剂量明显降低;SMART组的急性消化道反应(x2=9.965,P=0.019)和泌尿系统不良反应(x2=11.092,P=0.011)及骨髓抑制(x2 =9.071,P=0.028)均明显减少,差异均有统计学意义;SMART组的慢性消化道(x2=7.226,P=0.027)和泌尿系统不良反应(x2 =9.344,P=0.025)均明显减少,差异均有统计学意义.SMART与CRT组的CR(87.7％ vs72.1％,P=0.029)及近期有效率(98.5％ vs 86.9％,P=0.012)比较有统计学意义,SMART组明显提高.SMART组总的生存率(P=0.014)及无瘤生存率(P=0.001)均明显提高;1年生存率比较无统计学意义,x2=0.257,P=0.612;3年生存率(x2 =5.399,P=0.020)和5年生存率(x2=5.965,P=0.015)比较差异有统计学意义,SMART组明显提高.结论 SMART比较CRT,对中晚期宫颈癌合并盆腔淋巴结转移患者可获得理想的剂量分布,靶区可获得根治性剂量,邻近危及器官得到保护,急慢性毒副作用明显降低,完全缓解率及无瘤生存率明显提高.     

Combination external beam radiotherapy and high-dose-rate intracavitary brachytherapy for uterine cervical cancer: analysis of dose and fractionation schedule

PURPOSE: To determine an appropriate dose and fractionation schedule for a combination of external beam radiotherapy (EBRT) and high-dose-rate intracavitary brachytherapy (HDR-ICBT) for uterine cervical cancer. METHODS: Eighty-eight patients with uterine cervical squamous cell carcinoma treated with EBRT and HDR-ICBT were analyzed. Twenty-five patients were classified as early disease (nonbulky Stage I/II, less than 4-cm diameter) and 63 patients as advanced disease (greater than 4 cm diameter or Stage IIIB) according to the American Brachytherapy Society definition. Tumor diameter was measured by MRI. Pelvic EBRT was delivered before applications of ICBT. HDR-ICBT was performed once a week, with a fraction point A dose of 6 Gy. Source loadings corresponded to the Manchester System for uterine cervical cancer. No planned optimization was done. A Henschke-type applicator was mostly used (86%). Median cumulative biologic effective dose (BED) at point A (EBRT + ICBT) was 64.8 Gy(10) (range: 48-76.8 Gy(10)) for early disease, and 76.8 Gy(10) (range: 38.4-86.4 Gy(10)) for advanced disease. Median cumulative BED at ICRU 38 reference points (EBRT + ICBT) was 97.7 Gy(3) (range: 59.1-134.4 Gy(3)) at the rectum, 97.8 Gy(3) (range: 54.6-130.4 Gy(3)) at the bladder, and 324 Gy(3) (range: 185.5-618 Gy(3)) at the vagina. Actuarial pelvic control rate and late complication rate were analyzed according to cumulative dose and calculated BED. RESULTS: The 3-year actuarial pelvic control rate was 82% for all 88 patients: 96% for those with early disease, and 76% for advanced disease. For pelvic control, no significant dose-response relationship was observed by treatment schedules and cumulative BED at point A for both early and advanced disease. The 3-year actuarial late complication rates (Grade > or =1) were 12% for proctitis, 11% for cystitis, and 14% for enterocolitis. There were significant differences on the incidence of proctitis (p < 0.0001) and enterocolitis (p < 0.0001), but not for cystitis by the treatment schedules and cumulative point A BED. All 4 patients treated with 86.4 Gy(10) at point A suffered both proctitis and enterocolitis. Patients with cumulative BED at rectal point of > or =100 Gy(3) had significantly higher incidence of proctitis (31% vs. 4%, p = 0.013). CONCLUSIONS: In view of the therapeutic ratio, cumulative BED 70-80 Gy(10) at point A is appropriate for uterine cervical cancer patients treated with a combination of EBRT and HDR-ICBT. Present results and data from other literatures suggested that cumulative BED at the rectal point should be kept below 100-120 Gy(3) to prevent late rectal complication.     

Cervical tumor control evaluated with ICRU 38 reference volumes and integrated reference air kerma.

PURPOSE: The purpose of this investigation was to evaluate the relationship of ICRU 38 reference volumes and integrated reference air kerma to primary cervical tumor control. MATERIALS AND METHODS: This retrospective study includes 1253 women with carcinoma of the uterine cervix treated with radiotherapy. Patients were treated from 1959 to 1993 at the Mallinckrodt Institute of Radiology. There were 39 women with stage Ia disease, 211 with stage Ib1, 88 with stage Ib2, 580 with stage 2, and 335 with stage 3 disease. Most patients with stage Ia disease were treated with low dose rate brachytherapy alone. All other patients were treated with external irradiation and low dose rate brachytherapy. External irradiation doses ranged from 8.2-63.8 Gy to the whole pelvis and an additional parametrial boost to deliver a total of 65-75 Gy to Point P depending on tumor stage. Low dose rate brachytherapy was delivered to the primary tumor with doses ranging from 40x10(4)-60x10(4) Gy cm(2) (integrated reference air kerma; IRAK). Isodose reference volumes (60-160 Gy) and point A doses were determined for all patients. Tumor control was defined as control of the primary cervical cancer with or without failure at other pelvic or distant sites. RESULTS: The mean 60 Gy volume was calculated to be 139.5 cm(3) for stage Ia, 200.4 cm(3) for stage Ib1, 270.9 cm(3) for stage Ib2, 235 cm(3) for stage 2, and 293.4 cm(3) for stage 3. No patient with stage Ia disease had a failure in the cervix. For stage Ib1 tumors the mean 60 Gy volume was 219.1 cm(3) for those who failed in the cervix and 199.9 cm(3) for those who did not fail (P=0.73). For stage Ib2 tumors the mean 60 Gy volume was 354.4 cm(3) for those who failed and 260.2 cm(3) for those who did not fail (P=0.004). The mean 60 Gy volume was 249.3 cm(3) for those with stage 2 disease who failed and 233.8 cm(3) for those who did not fail (P=0.02). For patients with stage 3 cancer the mean 60 Gy volume was 321.6 cm(3) for those who failed and 287.3 cm(3) for those who did not fail (P=0.20). Reference volumes from 70-160 Gy were not statistically different within each stage for those who failed in the cervix compared to those who did not fail. Cervical recurrences by clinical stage did not have statistically significant differences for mean IRAK except for stage II disease (P=0.001). CONCLUSION: Analysis of the 60-160 Gy reference volumes and IRAK failed to demonstrate a consistent positive increasing correlation of these values to primary cervical tumor control.     

Combined intensity-modulated radiation therapy and brachytherapy in the treatment of cervical cancer

PURPOSE: This treatment planning study compared pseudo-step-wedge intensity modulation (PSWIM), intensity-modulated radiation therapy (IMRT), and conventional external irradiation, all combined with brachytherapy, for treatment of patients with cervical cancer. METHODS AND MATERIALS: This was a prospective study of 10 patients treated with PSWIM delivering 50.4 Gy to the pelvic lymph nodes and 20 Gy to the cervical tumor. This treatment was compared with a conventional treatment plan with a four-field box to 45 Gy and to an IMRT plan delivering 45 Gy. In each case, brachytherapy was prescribed to a total Point A low-dose-rate equivalent dose of 85 Gy. Total doses to Points A, Point P, the bladder point, and the rectal point were calculated. Acute toxicity and treatment response were prospectively recorded. RESULTS: The mean PSWIM total low-dose-rate equivalent dose to Points A and P (97.3 Gy and 65.1 Gy, respectively) was significantly higher, the mean rectal dose was the same, and the mean bladder dose was higher than with IMRT or four-field box. No acute toxicity of greater Grade 2, as defined by the than Radiation Therapy Oncology Group, was experienced. The positron emission tomography-based treatment response compared favorably with our institutional experience. CONCLUSIONS: Use of PSWIM and brachytherapy delivers significantly more dose to the tumor and lymph nodes than do competing techniques. Rectal doses are comparable. Maximum bladder point doses are higher. Toxicity and tumor response are acceptable.     

三维适形放疗结合252锎中子腔内后装照射治疗中晚期食管癌的临床研究

目的:探讨三维适形放疗结合锎(252Cf)中子腔内后装照射治疗中晚期食管癌的疗效、不良反应及晚期并发症。方法:92例中晚期食管癌患者全部采用三维适形放疗结合锎(252Cf)中子腔内后装照射治疗。三维适形放疗总剂量为45Gy-54Gy,分25-30次,5-6周完成;腔内照射3-4Gy/次,1次/周,共2-4次,总吸收剂量10Gy-16Gy。结果:治疗结束3个月进食梗阻缓解率为95%。近期疗效:完全缓解(CR)27%,部分缓解(PR)69.6%。1、2、3年局部控制率分别为82%、51%、32%;1、2、3年生存率分别为:78%、35%、18%;急性放射性食管炎发生率为54%;晚期食管狭窄发生率9%;食管穿孔发生率2%。结论:中晚期食管癌采用三维适形放疗结合锎(252Cf)中子腔内后装照射能够迅速而持久地缓解进食梗阻症状,提高局部控制率及生活质量,近期疗效显著,放疗不良反应未见明显增加。     

Fractionation in medium dose rate brachytherapy of cancer of the cervix

: To established an optimum fractionation for medium dose rate (MDR) brachytherapy from retrospective data of patients treated with different MDR schedules in comparison with a low dose rate (LDR) schedule.

: The study population consists of consecutive Stage IB-IIA-IIB patients who received radiotherapy alone with full dose brachytherapy plus external beam pelvic and parametrial irradiation from 1986–1993. Patients also receiving surgery or chemotherapy were excluded. The LDR group (n = 102, median follow-up: 80 months) received a median dose to Point A of 32.5 Gy fractions at 0.44 Gy/h plus 18 Gy of external whole pelvic irradiation. The MDR1 group (n = 30, median follow-up: 45 months) received a mean dose of two 32 Gy fractions at 1.68 Gy/h. An individual dose reduction of 12.5% was planned for this group according to the Manchester experience, but only a 4.8% dose reduction was achieved. The MDR2 group (n = 10, median follow-up: 36 months) received a dose of two 24 Gy fractions at 1.65 Gy/h. The MDR3 group (n = 10, median follow-up 33 months_ received a mean dose of three 15.3 Gy fractions at 1.64 Gy/h. And finally, the MDR4 group (n = 38, median follow-up: 24 months)_received six six 7.7 Gy fractions from two pulses 6 h apart in each of three insertions at 1.61 Gy/h/ The median external pelvic dose to MDR schedules was between 12 and 20 Gy. The linear quadratic (LQ) formula was used to calculate the biologically effective dose (BED) to tumor (BED) to tumor (Gy₁₀) and rectum (Gy₃), assuming T1/2 for REPAIR = 1.5 h.

: The crude central recurrence rate was 6% for LDR (mean BED - 95.4 Gy₁₀) and 10% for MDR4 (mean BED = 77.0 Gy₁₀ (p = NS). The remaining MDR groups had no recurrences. Grade 2 and 3 rectal or bladder complications were 0% for LDR (rectal BED = 109 Gy₃), 83% for MDR1 (BED = 206 Gy₃), and 30% for MDR3 (BED = 127 Gy₃). The MDR2 and MDR4 groups presented no complications (BED, 123 Gy₃, and 105 Gy₃, respectively). The LQ formula appears to correlate with late complications of the different MDR regimens. A BED above 125 Gy₃ was associated with Grade 2+3 rectal complications. Adequate central tumor control may be compromised with a tumor BED below 90–95 Gy₁₀.

: Medium dose rate brachytherapy at 1.6 Gy/h to point A has a marked dose ratre effect. Increased fractionation is the cost of overcoming the less favorable therapeutic ratio for MDR than for LDR. A larger (25%) reduction of brachytherapy dose than previously reported is also necessary. Our most recently developed schedule for Stage I–II patients is three insertions on three treatment days with six 8.0 Gy brachytherapy fractions, two on each treatment day, following or preceding an external whole pelvis dose of 18 Gy, and followed by additional external parametrial dose.     

The adverse effect of treatment prolongation in cervical cancer by high-dose-rate intracavitary brachytherapy.

BACKGROUND AND PURPOSE: The potential risk of prolongation of treatment time in cervical cancer has been reported for many low-dose rate (LDR) studies, with an estimated loss of local control ranging from 0.3 to 1.6% per day of treatment prolongation. Since the treatment schedule for fractionated high-dose rate intracavitary brachytherapy (HDRICB) is not directly comparable with that for low-dose rate studies, this report aims to evaluate the adverse effect of treatment prolongation specifically for cervical cancer treated with HDRICB. MATERIAL AND METHODS: From September 1992 to December 1997, 257 patients diagnosed with uterine cervical cancer (35 Ib, 26 IIa, 122 IIb, 10 IIIa, 57 IIIb, 7 IVa), who underwent external radiotherapy combined with between two and four courses of HDRICB and a minimum of 3 years of follow-up (median 57 months), were analyzed. Treatment consisted of irradiation of the whole pelvis with 44-45 Gy consisting of 22-25 fractions by 5 weeks, with the dose boosted to 54-58 Gy (with central shielding) for patients diagnosed as FIGO stage IIb-IVa bilateral parametrial disease. HDRICB was performed using an Ir-192 remote afterloading technique at 1-week intervals. The standard prescribed dose for each course of HDRICB was 7.2 Gy to point A for three insertions (before July 1995), or 6.0 Gy to point A for four insertions (after July 1995). Total prescribed point A doses (external beam radiotherapy+HDRICB) ranged from 58 to 71.6 Gy (median, 65.6 Gy) for stage IB-IIA, while analogous dosage for larger lesions (stage IIb-IVa) ranged from 59 to 75.6 Gy (median, 65.6 Gy). Kaplan-Meier and multivariate analyses were used to test the effect of treatment time on pelvic control rate (PCR) and cause-specific survival (CSS) at 5 years. RESULTS: Median treatment time was 63 days. For all stages of disease, the 5-year CSS and PCR were significantly different comparing treatment times of less than and greater than or equal to 63 days [83% and 65% (P=0.004], 93% and 83% (P=0.02), respectively]. These associations were also significant for stage Ib/IIa [97% and 79% (P=0.01), and 100% and 87% (P=0.02), respectively), but not for stage IIb [75% and 72% (P=0.79), and 93% and 87% (P=0.83), respectively] or stage III [66% and 49% (P=0.2), and 83% and 72% (P=0.21), respectively]. Multivariate analysis identified three prognostic factors for CSS, stage (P<0.001), tumor response to external RT (P=0.001), and overall treatment time (OTT; P=0.006). Prognostic factors for pelvic failure were stage (P<0.001), tumor response to external RT (P=0.001), and OTT (P=0.03). Prolongation of treatment time resulted in a daily decrease in pelvic control rate of 0.67% overall, and 0.43% for stage Ib-IIa, 0.57% for stage IIb, and 0.73% for stage III patients. CONCLUSION: Analysis of the data from the current study demonstrates that the adverse effect of treatment prolongation was observed later in the treatment course for the high-dose rate (HDR) series compared to the LDR analog, however, treatment-time prolongation still negatively influenced the cause-specific survival and pelvic control rate for both dosage groups.     

后程三维适形放疗结合化疗治疗67例中晚期宫颈癌的临床观察

目的:探讨不作腔内后装治疗的中晚期宫颈癌采用后程三维适形放疗结合化疗的疗效。方法:67例宫颈癌随机分为三维适形放疗加化疗组31例（适形组）与常规放疗加化疗组36例（常规组）,适形组患者均不作腔内后装治疗,先采用6MvX 线全盆腔放疗DT40Gy后采用三维适形放疗针对盆腔淋巴区及宫颈原发灶继续照射19Gy,最后再缩野针对宫颈原发灶推量,使宫颈原发灶总量达70～75Gy。常规组则采用全盆腔放疗40Gy后改为盆腔四野照射20Gy,腔内后装治疗A 点剂量30Gy/5 次,使宫颈原发灶A 点达70Gy。两组均作同期化疗,方案为:顺铂30mgd 1～3,5-FU 500mg/m2,d1～5,静脉滴注,第1 周、第5 周各一次。结果:适形组和常规组1、2 年生存率分别为93.5％、90.3％和83.3％、72.2％（P=0.198 和P=0.062）,无显著统计学意义。3 年生存率分别为87.1％和61.1％（P=0.017）,两组有显著的统计学意义。两组毒副作用比较,适形组Ⅰ～Ⅱ级放射性直肠炎及盆腔纤维化发生率低于常规组（P=0.000 和P=0.015）,其他的毒性相似。结论:后程三维适形放疗合并化疗治疗中晚期宫颈癌是一种有效、肯定的治疗方法,能提高患者近期生存率,晚期并发症较常规放疗低。3DCRT在宫颈癌放疗中的作用仍需大宗病例和长期随访来验证其优越性。      

Conservative treatment for lower gynecological tract malignancies in children and adolescents: the Institut Gustave-Roussy experience

Between 1972 and 1986, 37 patients with lower genital tract malignancies were treated with intracavitary or interstitial brachytherapy. Thirteen patients presented with clear cell adenocarcinoma, 14 patients with embryonal rhabdomyosarcoma, 6 patients with endodermal sinus tumor, 3 patients with sarcoma, and 1 patient with an undifferentiated tumor. FIGO classification was: Stage I, 16%; Stage II, 47%; and Stage III, 37%. Treatment policy included initial exploratory laparotomy with lymph node biopsy and ovarian transposition, chemotherapy (except in clear cell adenocarcinoma) and/or external radiotherapy prior to interstitial brachytherapy. Chemotherapy consisted of a combination of VAC-Ad (V = vincristine, A = D actinomycin, C = cyclophosphamide, Ad = adriamycin) in rhabdomyosarcoma and sarcomas, and MAC-Ad (M = methotrexate) in endodermal sinus tumor. External radiotherapy was used in seven patients: in one to reduce a bulky clear cell adenocarcinoma (20 Gy) and in six for pelvic nodal involvement (45 Gy). Brachytherapy techniques depended on tumor site and extent, and on the anatomy of the patients. Vulvar tumors were implanted with iridium-192 wires by an afterloading plastic tube technique. Cervical and vaginal tumors were treated with individually tailored moulded vaginal applicators loaded with either cesium-137 or iridium-192, with or without interstitial implants by plastic tube or guide gutter technique. Computerized dosimetry allowed calculation of treatment volumes and doses delivered on the tumor and adjacent critical organs. The prescribed dose (including external radiotherapy) was 60-75 Gy with 1-3 brachytherapy applications of a low dose rate (0.2 Gy/hr). Six patients are dead: one from chemotherapy complication, three of metastases (two sarcomas, one endodermal sinus tumor) and two of pelvic failures and metastases (two clear cell adenocarcinoma). The overall disease free 5-year survival is 72%. Actuarial 5-year local control is 84%, but including salvage is 94%: three (two rhabdomyosarcoma, one clear cell adenocarcinoma) of the five local failures were salvaged by surgery, chemotherapy and/or brachytherapy. Metastases occurred in six patients, one (sarcoma) salvaged by chemotherapy and external radiotherapy. Complications requiring surgery occurred in five patients: two hydronephroses, one urethral stricture, one ileo-cecal obstruction, and one vesicovaginal fistula. Twelve of the 17 patients (71%) over 12 years of age are normally menstruating. Two patients have produced three normal children. This multidisciplinary management of lower gynecological tract tumors including brachytherapy is both conservative and effective.     

252锎中子腔内照射加外照射治疗宫颈癌110例临床分析

目的 探讨252锎中子腔内照射加外照射治疗宫颈癌的疗效和并发症.方法 2002年11月至2007年11月间,252锎中子腔内照射加外照射治疗宫颈癌110例.全盆照射总剂量为20～30Gy后,中间挡铅4 cm,加量至45～54 Gy,每周4～5次,每次1.8 Gy.252锎中子腔内后装治疗采用SL(n)中子腔内治疗程序,每周1次腔内治疗,共6～10次,每次总剂量为6～8 Gy,A点总剂量为30～51 Gy,中位总剂量为42 Gy.结果 全组110例患者中位随访30个月,全组患者的3年总生存率为79.2%,其中Ⅰ期、Ⅱ期、Ⅲ期和Ⅳ期患者的3年生存率分别为50.0%、84.3%、53.7%和33.3%,Ⅱ 期和Ⅲ期患者间的差异有统计学意义(P＜0.05).全组患者的3年无病生存率为76.2%,其中Ⅱ期和Ⅲ期患者的3年无病生存率分别为80.4%和53.7%.全组患者的3年局部控制率为90.0%.治疗前血红蛋白水平正常者的3年生存率为78.2%,贫血者为42.4%,两组间差异有统计学意义(P＜0.05).病理类型为鳞癌和腺癌患者的3年生存率分别为78.5%和76.9%,肿瘤直径＜4 cm和≥4 cm患者的3年生存率分别为71.2%和68.1%,行介入治疗和未行介入治疗者的3年生存率分别为53.3%和74.5%,差异均无统计学意义(均P＞0.05).全组晚期放射性肠炎的发生率为11.8%,放射性膀胱炎的发生率为2.7%.结论 252锎是一种较好的腔内治疗的放射源,对于宫颈腺癌、直径≥4 cm的宫颈肿瘤以及受中子影响较大区域病变的治疗具有优势.     

Early results of pulsed-dose-rate interstitial brachytherapy for head and neck malignancies after limited surgery

PURPOSE: The aim of this study was to evaluate the relative incidence of toxicity and local control in patients with head and neck malignancies who underwent interstitial pulsed-dose-rate (PDR) brachytherapy (iBT). PATIENTS AND METHODS: From October 1997 to December 1998, 61 patients underwent interstitial PDR brachytherapy procedures in our department; 47 were patients with head and neck cancer. Forty patients received brachytherapy as part of their curative treatment regimen, and 7 patients were implanted for palliative purposes and excluded from the analysis of therapy efficacy. Twenty-four patients had interstitial brachytherapy procedures alone with D(REF) = 50 Gy; in 23 patients, iBT procedures were performed with D(REF) = 24 Gy in combination with external radiation. A dose per pulse (dp) of 0.5 Gy was prescribed for 38/47 patients, and a dp = 0.7 Gy for 9/47 patients. The pulses were delivered 24 h a day, with a time interval of 1 h between two pulses, resulting in an effective dose rate of 0.5 Gy/h or 0.7 Gy/h. A follow-up of the patients was done to analyze acute and delayed toxicity, local control, and survival. The analysis was performed after median follow-up of 12 months (5-18 months). RESULTS: After a median follow-up of 12 months, soft tissue necrosis was seen in one patient and bone necrosis in another. No other serious side effects were observed. Permanent locoregional tumor control was achieved in 37 of 40 patients. No distant metastases were observed. CONCLUSIONS: PDR interstitial brachytherapy with 0.5-0.7 Gy/h is a safe therapy. These preliminary results suggest that PDR interstitial brachytherapy of head and neck cancer is comparable with low-dose-rate (LDR) brachytherapy.     

鼻咽癌外照射加腔内近距离超分割推量照射的远期疗效分析

背景与目的:鼻咽癌的后装治疗一般采用鼻咽腔内治疗的方法进行推量照射,适用于局部早期鼻咽癌.福建省肿瘤医院率先开展鼻咽旁插植技术,无颅底破坏的局部晚期鼻咽癌采用后装治疗推量照射.本文分析腔内后装推量照射的远期疗效,探讨常规外照射的合适剂量配合后程超分割后装推量照射的临床价值.方法:1998年1月～2002年12月体外照射加腔内后装超分割推量放射治疗鼻咽癌患者352例,体外常规放射治疗50～70 Gy后进行腔内近距离超分割推量照射,外照射后咽旁间隙肿瘤残留者配合咽旁区插植放疗.采用个体化鼻咽腔内施源器,超分割照射每次2.5～3.0 Gy,2次/天,间隔6 h,总剂量5～32 Gy,中位剂量17 Gy.结果:本组l、2、3、5年生存率分别为97.0%、91.3%、87.6%、84.7%.总体5年生存率Ⅰ、Ⅱ期88.2%,Ⅲ、Ⅳ期79.2%(log-rank检验,P=0.016);总体局控率Ⅰ、Ⅱ期94.1%,Ⅲ、Ⅳ期91.7%(log-rank检验,P＞0.05).后组颅神经损伤32例(9.4%).结论:鼻咽腔内后装联合咽旁间隙捅植近距离放射治疗鼻咽癌取得良好的局控率和生存率,局部晚期鼻咽癌取得与早期鼻咽癌类似的局控率,咽旁间隙受累者咽旁插植增加颈动脉鞘区照射剂量,后组颅神经损伤发生率较高.     

Comparison of low and high dose rate brachytherapy in the treatment of uterine cervix cancer. Retrospective analysis of two sequential series

PURPOSE: This retrospective analysis aims to report on the comparative outcome of cervical cancer patients treated with low dose rate (LDR) and high dose rate (HDR) brachytherapy. METHODS AND MATERIALS: From 1989 to 1995, 190 patients were treated with low dose rate (LDR) brachytherapy (LDR group) and from 1994 to 2001, 118 patients were treated with high dose rate (HDR) brachytherapy (HDR group). FIGO stage distribution for the LDR group was Stage I: 6.3%; Stage II: 57.4%; and Stage III: 36.3% and for the HDR group Stage I: 9.3%; Stage II: 43.2%; and Stage III: 47.4%. All patients were treated with telecobalt external-beam radiotherapy (EBR). Median doses of LDR brachytherapy at Point A were 40 Gy and 50 Gy for patients treated with 1 and 2 implants, respectively. All patients from the HDR group were treated with 24 Gy in 4 fractions of 6 Gy to Point A. Survival, disease-free survival, local control, and late complications at 5 years, were endpoints compared for both groups. RESULTS: Median follow-up time for LDR and HDR groups was 70 months (range, 8-127 months) and 33 months (range, 4-117 months), respectively. For all stages combined, overall survival, disease-free survival, and local control at 5 years were better in the LDR group (69% vs. 55%, p = 0.007; 73% vs. 56%, p = 0.002; and 74% vs. 65%; p = 0.04, respectively). For clinical Stages I and II, no differences was seen in overall survival, disease-free survival, and local control at 5 years between the two groups. For clinical Stage III, overall survival and disease-free survival at 5 years were better in the LDR group than in the HDR group (46% vs. 36%, p = 0.04 and 49% vs. 37%, p = 0.03, respectively), and local control was marginally higher in the LDR group than in the HDR group (58% vs. 50%, p = 0.19). The 5-year probability of rectal complications was higher in the LDR group than in the HDR group (16% vs. 8%, p = 0.03) and 5-year probability of small bowel and urinary complications was not statistically different between the the LDR group and the HDR group (4.6% vs. 8.9%, p = 0.17 and 6% vs. 3%, p = 0.13, respectively). CONCLUSIONS: This comparative series suggests similar outcome for Stages I and II patients treated with either HDR or LDR brachytherapy. Lower overall and disease-free survival and marginally lower local control were observed for Stage III patients treated with HDR brachytherapy. Less late rectal complications were observed in the HDR group patients. These findings were probably the result of the relatively low HDR brachytherapy dose delivered at Point A.     

High-dose-rate intracavitary brachytherapy: results of analyses of late rectal complications

: To examine the incidence of radiation-induced late rectal complications by analyzing the data of measured rectal doses in patients with cancer of the uterine cervix treated with high-dose-rate intracavitary brachytherapy.

: We measured doses to the rectum in 105 patients with cancer of the cervix during high-dose-rate intracavitary brachytherapy with a semiconductor dosimeter that can measure five points in the rectum simultaneously. On the basis of these measurements, equivalent doses, to which the biologically equivalent doses were converted as if given as fractionated irradiation at 2 Gy/fraction, were calculated as components of the cumulative dose at five rectal points in intracavitary brachytherapy combined with the external whole pelvic dose.

: The calculated values of equivalent doses for late effects at the rectum ranged from 15 to 100 Gy (median 60 Gy for patients who did not develop complications and 76 Gy for patients who subsequently developed Grade II or III complications). When converted to a graph of absolute rectal complication probability, the data could be fitted to a sigmoid curve. The data showed a very definite dose-response relationship, with a threshold for complications at approximately 50 Gy and the curve starting to rise more steeply at approximately 60 Gy. The steepest part of the curve had a slope equivalent to approximately 4% incidence/1 Gy increase in equivalent doses.

: The radiation tolerance dose, 5% and 50% complication probability, was about 64 and 79 Gy, respectively. Our data almost agree with the prescribed dose for the rectum for the radiation tolerance doses on the basis of the recorded human and animal data. The probability of rectal complications increased drastically after the maximal rectal dose was >60 Gy.     

The impact of gap duration on local control in anal canal carcinoma treated by split-course radiotherapy and concomitant chemotherapy

PURPOSE: To investigate the potential benefit of reducing the intersequence gap in patients with anal cancer treated with split-course chemoradiotherapy. METHODS: The study group consisted of 90 patients with anal squamous carcinoma treated between 1981 and 1998, using concomitant chemotherapy (CT) and radiation (RT). Median age was 65 years (range 41-87). RT was delivered in a split course, with a median gap of 37.5 days (range 4-97) between sequences. First (pelvic) sequence delivered a median dose of 40 Gy (range 36-50.4), using AP/PA megavoltage photon beams. Boost treatment (median dose 20 Gy, range 13-26) consisted of either Iridium-192 implantation (49 patients) or external beam RT (41 patients). CT consisted of 1-2 cycles of a 5-day continuous infusion of 5-fluorouracil and bolus mitomycin C, usually administered during the first week of each RT course. Median follow-up was 76.2 months. Univariate and multivariate analyses were performed to determine the factors associated with locoregional control (LRC). RESULTS: Five-year actuarial LRC was 72.5%. Factors associated with poorer LRC (univariate) were: age < or = 65, male gender, and gap > 37.5 days. Number of CT cycles (1 vs. 2 or more), boost technique (brachytherapy vs. external), and T-stage were not significantly associated with LRC. In multivariate analysis, only age (p = 0.01), and gap (p = 0.02) retained their significance. In patients older than 65 years, LRC was 92.3% and 75% for shorter and longer gaps, respectively. In younger patients, the corresponding values for LRC were 73.7% and 50%. CONCLUSION: In anal cancers, split-course RT with > 50 Gy dose delivery is difficult to avoid because of acute toxicity. The present analysis suggests that shortening the gap contributes to optimizing LRC. Gaps longer than 5 weeks correlated with poorer LRC, with especially unsatisfactory results observed in younger patients.     

Two fractions of high-dose-rate brachytherapy in the management of cervix cancer: clinical experience with and without chemotherapy

PURPOSE: In recent years, high-dose-rate brachytherapy has become popular in the management of carcinoma of the uterine cervix, because it eliminates many of the problems associated with low-dose-rate brachytherapy. However, the optimum time-dose-fractionation remains controversial. Two fractions of high-dose-rate brachytherapy are convenient for patients, but most radiation oncologists in the United States do not use them, because of fear that they could lead to excessive rectal or bladder toxicity. Here we present our experience, which suggests that a two-fraction regimen is indeed safe and effective. METHODS: We treated 49 patients with Stages I-III biopsy-proven carcinoma of the uterine cervix by external beam radiation therapy (EBRT), plus two fractions of high-dose-rate brachytherapy. The histology was squamous cell carcinoma in 43 patients (88%) and nonsquamous in 6 (12%). The median size of the primary tumor was 6 cm (range: 3-10 cm). Each patient received EBRT to the pelvis to a median dose of 45 Gy (range: 41.4-50.4 Gy), followed by a parametrial boost when indicated. Thirty patients (61%) also received irradiation to the para-aortic lymph nodes to a dose of 45 Gy. After EBRT, each patient underwent two applications of high-dose-rate brachytherapy, 1 week apart. The dose delivered to point A was 9 Gy per application for 49 applications (50%) and 9.4 Gy for 43 applications (44%), and it varied from 7 to 11 Gy for the rest (6%). The total dose to the rectum from both high-dose-rate brachytherapy applications ranged from 4.7 to 11.7 Gy (median: 7.1 Gy), and the total dose to the bladder from 3.8 to 15.5 Gy (median: 10.5 Gy). Twenty-five of the 49 patients (51%) received concomitant chemotherapy (cisplatin 20 mg/m(2)/day for 5 days) during the first and fourth weeks of EBRT and once after the second high-dose-rate brachytherapy application. Chemotherapy was not assigned in a randomized fashion. The use of chemotherapy increased during the time period spanned by this study as increasing evidence supporting the use of chemotherapy began to appear. RESULTS: The observed survival rates after 2, 3, and 5 years were 83%, 78%, and 78%, respectively. The surviving patients have been followed up for a median of 3 years (range: 2-6 years). Eight of the 49 patients suffered local failures. Among patients treated without chemotherapy, the 3-year local control rate was 77%; it was 88% among those receiving chemotherapy. There have been no regional failures. Four patients developed distant metastases. At 3 years, 91% of the patients in each group were free of distant metastases. Ten of the 49 patients (20%) suffered Grade 3 acute toxicity; 11 (22%) had Grade 4. Among the 24 patients treated without chemotherapy, only 1 (4%) suffered Grade 3 toxicity. Among the 25 patients receiving chemotherapy, in contrast, 8 (32%) suffered Grade 3 and 12 (48%) Grade 4 acute toxicity. Only 2 patients suffered late toxicity: One suffered Grade 2 and the other Grade 3 late toxicity. The actuarial risk of Grade 2 or worse late toxicity was 5%, with or without chemotherapy. CONCLUSIONS: Our experience suggests that two fractions of high-dose-rate brachytherapy are safe and effective in the management of cervix cancer, even in conjunction with concomitant cisplatin. The fears that the use of two fractions would lead to excessive rectal or bladder toxicity proved unfounded. Guidelines for ensuring a low complication rate are discussed.     

Tolerance of pelvic normal tissues to hyperfractionated radiation therapy: results of Protocol 83-08 of the Radiation Therapy Oncology Group

A prospective, centrally randomized Phase I/II trial of hyperfractionation in definitive radiation therapy for locally advanced squamous and transitional cell carcinoma of the bladder was conducted by the Radiation Therapy Oncology Group (RTOG) from April 1983 through June 1986. Patients with T3-4 and T2 N+ (AJC) histologically-confirmed cancer of the bladder received twice daily radiation therapy with 1.2 Gy per fraction and a minimum of 4 hr between fractions. All patients received a whole pelvic total dose of 50.4 Gy: Total doses to reduced volumes were 60.0 Gy, 64.8 Gy, or 69.6 Gy. Of 54 patients entered, 50 were eligible. An unbalanced treatment assignment was used: Nine patients received 60.0 Gy, 15 patients received 64.8 Gy and 26 received 69.6 Gy. Performance status (Karnofsky) was 90-100 in 72% of patients and 92% had transitional carcinoma. Eighty percent of tumors were T3 or T4. Observation of at least 18 months was available for 26 patients. Grade 3 acute reactions (within 90 days) were reported in eight patients (one at 60.0 Gy, three at 64.8 Gy and four at 69.6 Gy). Five patients experienced a total of seven major late effects--four Grade 3 and three Grade 4. The cumulative probability of Grade 3 and 4 late complications of treatment for the 46 patients at risk for late complications was 5% +/- 3% at 6 months, 7% +/- 4% at 12 months, and 10% +/- 5% at 18 and 24 months. The cumulative probability of Grade 3 or 4 late complications for patients who received a total dose of 69.6 Gy was 5% +/- 4% at 6 and 12 months and 11% +/- 8% at 18 and 24 months. Only one patient who experienced major late effects was also reported to have major acute reactions. Comparisons of survival of patients treated in the current study with those who received 60 Gy in 30 fractions in 6 weeks in RTOG Protocol 71-04, did not suggest any deleterious effects from hyperfractionated radiation therapy to the pelvis. The normal pelvic tissues tolerated hyperfractionated radiation therapy sufficiently well to justify exploring it, alone and with brachytherapy, in other pelvic tumors.     

Adenocarcinoma of the endometrium treated with combined irradiation and surgery: study of 437 patients

PURPOSE: To identify prognostic factors and treatment toxicity in a series of operable endometrial adenocarcinomas. METHODS AND MATERIALS: Between November 1971 and October 1992, 437 patients (pts) with endometrial carcinoma, staged according to the 1988 FIGO staging system (225 Stage IB, 107 Stage IC, 4 Stage IIA, 35 Stage IIB, 30 Stage IIIA, 6 Stage IIIB, and 30 Stage IIIC), underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy without (n = 140) or with (n = 297) pelvic lymph node dissection. The chronology of adjuvant RT was not randomized and depended on the usual practices of the surgical teams. Seventy-nine pts (Group I) received preoperative low-dose-rate uterovaginal brachytherapy (mean dose [MD]: 57 Gy). Three hundred fifty-eight pts (Group II) received postoperative RT. One hundred ninety-six pts received low-dose-rate vaginal brachytherapy alone (MD: 50 Gy). One hundred fifty-eight pts had external beam pelvic RT (MD: 46 Gy) followed by low-dose-rate vaginal brachytherapy (MD: 17 Gy). Four pts had external beam pelvic RT alone (MD: 47 Gy). The mean follow-up from the beginning of treatment was 128 months. RESULTS: The 10-year disease-free survival rate was 86%. From 57 recurrences, only 12 were isolated locoregional recurrences. The independent factors decreasing the probability of disease-free survival were as follows: histologic type (clear-cell carcinoma, p = 0.038), largest histologic tumor diameter >3 cm (p = 0.015), histologic grade (p = 0.008), myometrial invasion > 1/2 (p = 0.005), and 1988 FIGO staging system (p = 9.10(-8)). In Group II, the addition of external beam pelvic RT did not seem to independently improve vaginal or pelvic control. The postoperative complication rate was 7%. The independent factors increasing the risk of postoperative complications were stage FIGO (p = 0.02) and pelvic lymph node dissection (p = 0.011). The 10-year rate for Grade 3 and 4 late radiation complications according to the LENT-SOMA scoring system was 3.1%. External beam pelvic RT independently increased the rate for Grade 3 and 4 late complication (RR: 5.6, p = 0.0096). CONCLUSION: Postoperative external beam pelvic RT increases the risk of late radiation complications. After surgical and histopathologic staging with pelvic lymph node dissection, in subgroup of "intermediate-risk" patients (Stage IA Grade 3, IB-C and II), postoperative vaginal brachytherapy alone is probably sufficient to obtain a good therapeutic index. Results for patients with Stage III tumor are not satisfactory.     

Chemo-reirradiation in persistent/recurrent head and neck cancers

BACKGROUND: This retrospective study was carried out to evaluate the feasibility and safety of chemo-reirradiation as a salvage treatment in patients with persistent/recurrent head and neck cancers. METHODS: From 1991 to 1999, records of 131 patients with head and neck carcinoma who had loco-regional persistent/recurrent disease following curative therapy were analyzed. Of these, 33 patients had received chemo-reirradiation. Four patients were further excluded as they had been reirradiated by brachytherapy or external radiotherapy alone. The remaining 29 patients received reirradiation along with chemotherapy. They were evaluated for toxicity profile, post-salvage survival and overall survival. RESULTS: The median reirradiation dose was 34 Gy (range, 12-50 Gy) and median cumulative RT dose was 104 Gy (range, 72-124 Gy). The median for chemotherapy cycles was four. Grade 2/3 mucositis, dermatitis, neutropenia were seen in 10%, 7% and 3% of patients, respectively. An overall response rate was seen in 83% of patients with complete response in 31%. All complete responders had received a cumulative RT dose of >/=100 Gy. Those patients who were initially treated by external radiation alone benefited with subsequent chemo-reirradiation with a complete response rate of 54%. The median post-salvage overall survival was 9 months with the 1- and 2-year survival rates being 41% and 12%, respectively. The post-salvage disease free survival (P = 0.01) and overall survival (P = 0.008) were also significantly better in patients who were treated initially by external radiotherapy alone. CONCLUSIONS: Chemo-reirradiation appears feasible and effective in patients treated previously with external radiotherapy but needs proper patient selection. Patients should be given optimum reirradiation dose, with cumulative doses of >/=100 Gy, along with chemotherapy. This study warrants the need for more prospective trials.