Combined modality treatment in unresectable extrahepatic biliary carcinoma

PURPOSE: Cancers of the extrahepatic biliary tract are rare. Surgical resection is considered the standard treatment, but is rarely feasible. Several reports of combined modality therapy, including external beam radiation, often combined with chemotherapy and intraluminal brachytherapy, have been published. The purpose of this study was to evaluate the effect of chemoradiation plus intraluminal brachytherapy on response, local control, survival, and symptom relief in patients with unresectable or residual extrahepatic biliary carcinoma. METHODS AND MATERIALS: From February 1991 to December 1997, 20 patients (14 male, 6 female; mean age 61 +/- 12 years; median follow-up 71 months) with unresectable (16 patients) or residual (4 patients), nonmetastatic extrahepatic bile tumors (common bile duct, 8; gallbladder, 1; Klatskin, 11) received external beam radiation (39.6-50.4 Gy); in 19 patients, 5-fluorouracil (96-h continuous infusion, days 1-4 at 1,000 mg/m(2)/day) was also administered. Twelve patients received a boost by intraluminal brachytherapy using (192)Ir wires of 30-50 Gy, prescribed 1 cm from the source axis. RESULTS: During external beam radiotherapy, 8 patients (40%) developed grade 1-2 gastrointestinal toxicity. Four patients treated with external-beam plus intraluminal brachytherapy had a clinical response (2 partial, 2 complete) after treatment. For the total patient group, the median survival and time to local progression was 21.2 and 33.1 months, respectively. Distant metastasis occurred in 10 (50%) patients. Two patients who received external beam radiation plus intraluminal brachytherapy developed late duodenal ulceration. Two patients with unresectable disease survived more than 5 years. CONCLUSION: Our data suggest that chemoradiation plus intraluminal brachytherapy was relatively well-tolerated, and resulted in reasonable local control and median survival. Further follow-up and additional research is needed to determine the ultimate efficacy of this regimen. New chemoradiation combinations and/or new treatment strategies (neoadjuvant chemoradiation) may contribute, in the future, to improve these results.     

Intraluminal low-dose-rate 192Ir brachytherapy combined with external beam radiotherapy and biliary stenting for unresectable extrahepatic bile duct carcinoma

PURPOSE: To evaluate the results of combined-modality therapy, including external beam radiotherapy, intraluminal (192)Ir, and biliary stenting for extrahepatic bile duct carcinoma. MATERIALS AND METHODS: Between 1988 and 1998, 93 patients with unresectable extrahepatic bile duct carcinoma underwent definitive radiotherapy. The dose of external beam radiotherapy was 50 Gy in 25 fractions. Low-dose-rate (192)Ir was delivered at a dose of 27-50 Gy (mean 39.2) at 0.5 cm from the source. An expandable metallic endoprosthesis was used to establish an internal bile passage. RESULTS: The median survival was 12 months, with a 1-, 3-, and 5-year actuarial survival rate of 50%, 10%, and 4%, respectively. Tumor length, hepatic invasion, and distant metastasis significantly affected survival. Ninety-six percent of patients could successfully remove external drainage catheters. The actuarial biliary patency rate for these patients at 1, 3, and 5 years was 52%, 29%, and 18%, respectively. Tumor length, tumor diameter and T stage were significantly associated with the patency rate. Mild-to-severe gastroduodenal complications were observed in 32 patients and were significantly associated with the active length of (192)Ir and linear source activity. Eight patients had treatment-related biliary fistula. CONCLUSIONS: Our combined-modality therapy provided reasonable local control and improved the quality of life of patients with extrahepatic bile duct carcinoma. Because none of the treatment characteristics had any impact on survival or biliary patency, lower dose levels and/or a localized target volume are recommended to minimize morbidity.     

Chemoradiation and brachytherapy in biliary tract carcinoma: long-term results

PURPOSE: To evaluate long-term effects of chemoradiation and intraluminal brachytherapy in terms of local control, disease-free survival, overall survival, and symptom relief in patients with unresectable or residual extrahepatic biliary carcinoma. METHODS AND MATERIALS: Twenty-two patients with unresectable (17 patients) or residual (5 patients) nonmetastatic extrahepatic bile tumors received external beam radiation therapy (39.6-50.4 Gy) between 1991 and 1997. In 21 patients, 5-fluorouracil (96-h continuous infusion, Days 1-4, 1,000 mg/m2/day) was administered. Twelve patients received a boost of intraluminal brachytherapy with 192Ir wires (30-50 Gy) 1 cm from the source axis. RESULTS: During external beam radiotherapy, 10 patients (45.4%) developed Grade 1 to 2 gastrointestinal toxicity. In patients with unresectable tumor who could be evaluated, the clinical response was 28.6% (4 of 14). Two patients showed complete response. In all 22 patients, median durations of local control, disease-free survival, and overall survival were 44.5 months, 16.3 months, and 23.0 months, respectively. Two patients who received external beam radiation therapy and intraluminal brachytherapy developed late duodenal ulceration. In patients with unresectable tumors, median survival was 13.0 months and 22.0 months in those treated with and without brachytherapy, with 16.7% and no 5-year survival, respectively (p=0.607). Overall 5-year survival was 18.0%: 40% and 11.7% in patients treated with partial resection and in those with unresectable tumor, respectively (p=0.135). CONCLUSION: This study confirmed the role of concurrent chemoradiation in advanced biliary carcinoma; the role of intraluminal brachytherapy boost remains to be further analyzed in larger clinical trials.     

经导管~(192)Ir近距离放射治疗局部晚期肝门部胆管癌

目的：观察局部晚期肝门部胆管癌姑息性引流术后１９２Ｉｒ腔内放疗的疗效。方法：先行手术探查尽可能刮除肿瘤并放置Ｕ型管引流，术后再经导管腔内放疗。参考点距离放射源中心轴１０ｍｍ，总量２４～３０Ｇｙ／３次。３例配合肝动脉区域性灌注化疗，１例配合外照射ＤＴ４５Ｇｙ／４．５周。结果：生存期６～２６个月，中位生存期１１．５月。１５例死亡，１例目前存活８个月。全组１年生存率３７．５％，２年生存率６．０％，结论：局部晚期肝门部胆管癌姑息性引流术后腔内放疗可提高生存期及生活质量     

Ultrasound directed extrahepatic bile duct intraluminal brachytherapy.

Intraluminal brachytherapy with a transcatheter Iridium-192 (Ir-192) wire, as a method to deliver a boost to patients with tumors of the extrahepatic bile ducts, has been well described. A major limitation of current imaging techniques is the inability to accurately define the proximal, distal, and most importantly the lateral extent of the tumor. We have found endoluminal ultrasound, which to this date has been used primarily to measure arterial wall layers, can successfully determine tumor volume in the bile ducts. The small diameter of these ultrasound probes allows easy insertion into a biliary duct drainage tube. Given the uncertainties in the determination of tumor size in the bile ducts, ultrasound is an ideal method by which to obtain the measurements. We present a case of recurrent islet cell carcinoma treated with external beam radiation therapy and an Ir-192 intraluminal brachytherapy boost in which the ultrasound probe was used to determine the tumor volume and response to therapy.     

肝外胆管癌的放射治疗：附12例分析

During the past 8 years, 12 patients with extrahepatic bile duct adenocarcinoma which was contra-indicated to operation or who underwent conservative resection wer treated by radiotherapy in our hospital. Five patients were given post-operative radiation of 60-70 Gy/7-9 weeks, 3 patients received 12 Mev beta beam of one single 30 Gy intra-operative radiotherapy and 4 were treated by intra-operative radiotherapy of 20 Gy plus external irradiation of 40 Gy/5 weeks after the operation. The results indicated that most of the patients died around 1 year and 2 are still alive for over 2 years. The present results are more favorable as compared with those treated before 1980 because biliary drainage had been done before timely high dose radiotherapy after the operation. The author considers that intra-operative radiotherapy or its combination with external irradiation might be helpful to improve the prognosis in extrahepatic bile duct cancer.     

Radiation therapy for primary carcinoma of the extrahepatic biliary system. An analysis of 63 cases

From 1976 to 1988, 63 patients received radiation therapy for primary cancers of the extrahepatic biliary system (eight gallbladder and 55 extrahepatic biliary duct). Twelve patients underwent orthotopic liver transplantation. Chemotherapy was administered to 13 patients. Three patients underwent intraluminal brachytherapy alone (range, 28 to 55 Gy). Sixty patients received megavoltage external-beam radiation therapy (range, 5.4 to 61.6 Gy; median, 45 Gy), of whom nine received additional intraluminal brachytherapy (range, 14 to 45 Gy; median, 30 Gy). The median survival of all patients was 7 months. Sixty patients died, all within 39 months of radiation therapy. One patient is alive 11 months after irradiation without surgical resection, and two are alive 50 months after liver transplantation and irradiation. Symptomatic duodenal ulcers developed after radiation therapy in seven patients but were not significantly related to any clinical variable tested. Extrahepatic biliary duct cancers, the absence of metastases, increasing calendar year of treatment, and liver transplantation with postoperative radiation therapy were factors significantly associated with improved survival.     

腔内放疗与体外放疗结合全身化疗治疗中晚期中央型肺癌的研究

目的探讨全身化疗结合支气管腔内放疗治疗不能手术的中晚期中央型肺癌的安全性、近期疗效、毒副反应和适应证。方法选用铂类为主的全身化疗方案同时经纤维支气管镜置入施源管、模拟定位机定位后用192铱后装治疗机行腔内局部放疗3~5次(1次/周),单次剂量5Gy~7Gy,参考点在0.5cm~1.0cm。化疗每3~4周一周期,3~4个周期为一疗程,一个疗程后评估近期疗效、毒副反应。结果腔内放疗组52例全部有效,完全缓解46例(88.46%)、部分缓解6例(11.54%);阻塞症状和咳嗽在首次腔内放疗后能明显缓解。体外放疗组64例中,有效者59例(92.2%),完全缓解45例(70.3%)、部分缓解14例(21.87%),无变化者5例;32例阻塞症状和咳嗽在体外放疗后2周左右开始减轻,两者近期客观疗效比较无显著性差异。毒副作用白细胞减少腔内放疗组1级、2级、3级白细胞降低为21/52、19/52、3/52;体外放疗组分别为6/64、26/64和32/64;两者比较有显著性差异。放射性肺炎腔内放疗组无放射性肺炎发生,体外放疗组64例中有63例发生(98.4%);放射性食道炎腔内治疗组52例有2例发生;体外治疗组全部出现了放射性食道炎,两者比较有显著性差异。结论全身化疗结合腔内放疗治疗中晚期中央型肺癌安全,近期疗效明显,减少体外放疗所导致的放射性肺炎、放射性食道炎的发生和减低白细胞的下降程度,改善病人生活质量。     

The role of radiotherapy in the treatment of bile duct carcinoma

Forty-two patients with irresectable bile duct carcinoma (n = 31) or with microscopic evidence of tumor rest after aggressive surgery for bile duct carcinoma (n = 11) were given radiotherapy consisting intentionally of external-beam therapy and intraluminal 192Iridium (192Ir) wire application(s) following bile drainage procedures. The treatment was well tolerated; complications were mainly infectious and related to the success of the drainage. A median survival of 10 months was achieved for the group as a whole. Patients treated following microscopically incomplete resection survived longer than patients with an irresectable tumor (15 vs 8 months median survival, p = 0.06). Gross lymph node involvement also proved to be a prognostic factor.     

以顺铂为基础不同化疗方案同期放化疗治疗局部中晚期子宫颈癌临床研究

目的 探讨单药顺铂与TP(紫杉醇+顺铂)方案同步放化疗治疗中晚期子宫颈癌的临床疗效及不良反应比较.方法 随机入组44例局部中晚期子宫颈癌患者随机给予单药顺铂方案或TP方案化疗,两组同期放疗均采用盆腔外照射+高剂量率腔内后装.结果 所有患者均完成治疗,治疗结束3月评价其有效率,TP组为66.7 ％,顺铂组为55.0％.1年生存率分别为88.3％、70.0％,差异无统计学意义(P值＞0.05).毒副反应主要是粒细胞减少、胃肠道反应.同期放化疗期间TP组、单药顺铂组发生Ⅲ～Ⅳ度粒细胞减少和Ⅲ～Ⅳ度胃肠道反应分别为16.7％vs5.0％(P＞O.05),12.5％ vs 5.0％(P＞0.05).结论 TP方案与单药顺铂同期放化疗治疗局部中晚期子宫颈癌患者的疗效比较,前者的近期疗效及1年生存率均较后者有所提高,差异无统计学意义(P＞0.05),但从百分率来看,TP组在近期疗效及1年生存率方面均有升高的趋势.尽管联合化疗方案中出现Ⅲ、Ⅳ度放化疗反应的病例数较单药组有所增加,但可以耐受,不影响治疗的完成.     

Analysis of failure following curative irradiation of gallbladder and extrahepatic bile duct carcinoma

Twenty patients with carcinoma of the gallbladder (GB-4 patients) or extrahepatic bile ducts (EHBD-16 patients) received radiation therapy with curative intent between January, 1980 and December, 1982. All 20 received 4500–5000 rad in 180–200 rad fractions to the tumor and regional lymph nodes. A 1000 to 1500 rad external beam boost was delivered in 180–200 rad fractions in 10 patients who received external beam alone or concomitant 5-Fluorouracil (5-FU). Three of the four GB and 5 of the 16 EHBD patients received a transcatheter boost with 192-Iridium (¹⁹²Ir) to a dose of 2000–2500 rad calculated at a 0.5-0.1 cm radius. An additional 2 patients with EHBD lesions received an intraoperative electron (IORT) boost of 1500–2000 rad in one fraction calculated to the 90% isodose. Survival and patterns of failure were analyzed by site and treatment method. All four patients with GB carcinoma are dead of disease at 5$\text{1}\text{2}$, 6, 9 and 10 months from the date of diagnosis respectively. Three of the four developed diffuse peritoneal carcinomatosis. Five of the 16 patients with EHBD carcinoma are alive with a median follow-up of 18 months (range 6–23 months). Four of the 5 patients received a transcatheter ¹⁹²Ir or IORT boost and all are without evidence of disease. Four of 9 patients who had a subtotal resection with transection of tumor, dilatation of the bile ducts with probes or curettement of the bile ducts developed either diffuse peritoneal carcinomatosis (3 patients) or a recurrence in the surgical scar (2 patients). Local failure was documented in 3 of the nine patients treated with external beam alone ±5-FU, and has been documented in one of the seven patients who received an IORT or transcatheter ¹⁹²Ir boost. Further experience is necessary to determine whether this aggressive treatment will result in long-term disease-free survival in these patients.     

Advanced hepatocellular carcinoma--feasibility and clinical impact of high-dose-rate brachytherapy on the treatment of lesions growing into biliary trees, portal veins and the vena cava]

This study was performed to evaluate the feasibility and clinical impact of intraluminal and endovascular high-dose-rate iridium-192 brachytherapy on the treatment of HCC lesions growing into biliary trees, portal veins and the inferior vena cava. HCCs involving biliary trees in 2 patients, the main and/or first-order portal veins in 3 patients, and the inferior vena cava in 2 patients. Brachytherapy was percutaneously performed with a 5F applicator, which was placed adjacent to the lesions. A mean total dose of 23 Gy (range, 5-7 Gy/fr) was irradiated (at a 5 mm radius) to the biliary or the portal venous tumors. A total dose of 10 Gy (5 Gy/fr) was given to the caval tumors. External-beam radiotherapy was combined in 2 patients with caval lesions, stent placement in 2 patients with biliary lesions and hepatic arterial infusion chemotherapy in 5 patients. There was no major complication except hemobilia, which ceased after placing a PTCD tube in the bile duct in one patient. All tumors were significantly reduced in size and remained controlled during the period of patients' survival. Complete tumor necrosis was histologically proved in 2 autopsy cases having biliary lesions. The median survival was 13 months. Intraluminal and endovascular high-dose-rate brachytherapy appears to be a feasible, and effective procedure to treat advanced HCCs invading biliary trees, portal veins and the vena cava.     

Intraluminal brachytherapy boost following external beam radiotherapy with concurrent chemotherapy of oesophagus carcinoma: Results of a prospective observational study

Purpose

The main objective of our study is to evaluate response and toxicity profile in patients receiving external beam radiotherapy with concurrent chemotherapy followed by intraluminal brachytherapy boost for a carcinoma of the oesophagus.

外放射结合腔内照射治疗气管癌和支气管肺癌的疗效观察

目的 探讨气管癌、支气管肺癌腔内放射治疗的价值。方法 4例原发气管癌和22例原发支气管肺癌及14例(18处病变)支气管肺癌术后复发者，外放射采用6MV X射线，剂量为DT30～77Gy(平均52Gy)；腔内照射采用低剂量率^192Ir小线源(1．48BGq)，支气管黏膜参考点剂量为4～6Gy／次，总剂量10～53Gy(中位值28Gy)。结果 37例肿瘤完全消退(CR)，2例部分消退(PR)，1例轻微变化(MR)，3、5年局部控制率分别为75％和65％。23例生存时间≥3年，3年生存率为57．5％。并发症较少见。结论 外放射结合腔内照射治疗对于早期支气管肺癌、局限性气管癌和支气管肺癌术后复发者是有效的治疗手段．长期生存是可能的。     

肝外胆管癌的介入治疗现状与展望

肝外胆管癌是指源于肝外胆管包括肝门区至胆总管下端胆管的恶性肿瘤.在美国癌症联合会(American Joint Committee on Cancer,AJCC)第8版指南中,肝外胆管癌被分类分为肝门胆管癌和远端胆管癌两部分.近年来,肝外胆管癌的发病率逐渐升高,且预后较差,手术切除在治疗中的局限性逐渐体现.在胆管癌的诊...     

腔内近距离放疗结合体外放疗及同步化疗治疗中央型肺癌

目的 探讨腔内近距离放疗配合体外放疗和同步化疗治疗中央型肺癌的疗效.方法 42例中央型肺癌患者随机分为治疗组和对照组.采用腔内近距离放疗配合体外放疗和同步化疗治疗累及气管、支气管的中央型肺癌21例.结果 治疗组和对照组总有效率分别为85.7%和57.1%,差异有统计学意义(P＜0.05).主要不良反应为刺激性剧烈咳嗽和骨髓抑制.结论 腔内近距离放疗中央型肺癌能迅速改善由气道阻塞引起的临床症状,与体外放疗和同步化疗联合应用能达到较好的治疗效果.     

High-dose-rate intraluminal brachytherapy for bile duct carcinoma after surgery.

Five patients with recurrent or residual bile duct carcinoma after surgery were treated with high-dose-rate intraluminal brachytherapy (HDRIBT) using a remote afterloader. External radiotherapy was also given in three cases. HDRIBT is considered to be an effective mode of radiotherapy for residual or recurrent bile duct tumors.     

Clinical study on radiotherapy combined with surgical treatment of 162 patients with cervical cancer

Objective: To compare the 5-year survival rates and complications of internal and external irradiation therapy combined with operation in patients with Ⅱ-Ⅲ period of cervical cancer.Methods: 162 cervical cancer patients after the whole palace resection pelvic lymphadenectomy were divided into three groups, and then accepted radiotherapy.The first group with 91 cases was accepted internal and external irradiation therapy before operation; the second group with 37 cases was given internal irradiation therapy before operation; the third group with 34 cases was given routine postoperative radiotherapy.External irradiation used 60Co irradiation or a linear accelerator, to the whole basin, and the irradiation dose of "B" point in preoperative radiotherapy was 26-30 Gy, in postoperative radiotherapy was 46-50 Gy; intraluminal brachytherapy used 192lr,the dose of "A" point was 5-15 Gy.Results: The 5-year survival rate of preoperative combined radiotherapy group was 78.0%(71/91), preoperative intracavitary radiotherapy group 64.9% (24/37), and postoperative radiotherapy group 35.3% (12/34).Comparing the 5-year survival rates of the preoperative combined and postoperative irradiation groups, there was significant difference (P＜0.05).The major complications were radioactive proctitis and cystitis, the complication incidences of three groups were 35.2% (32/91), 32.4% (12/37), 38.2% (13/34), respectively, and the differences were not statistically significant (P＞0.05).Conclusion: The intraluminal brachytherapy plus external irradiation can significantly increase the 5-year survival rate of patients with Ⅱa-Ⅲa stages, and the incidence of complications was not significant difference.     

Brachytherapy of glioblastoma recurring in previously irradiated territory: predictive value of tumor volume

PURPOSE: To evaluate the impact of tumor volume on survival of patients reirradiated with (192)Ir for recurrent glioblastoma. METHODS AND MATERIALS: Between 1993 and 1997, 42 patients with recurrent glioblastomas (29 males and 13 females, age 18-69 years, median age 49) were treated with (192)Ir implantation. Previous treatments included surgery, external beam radiotherapy, and chemotherapy. Maximum diameter of the recurrent tumor was 1.2-10.1 cm (median: 5.7 cm) and tumor volume was 1.6-122 cm(3) (median: 23 cm(3)). Karnofsky performance status score was 50-100 (median: 80). Brachytherapy dose was 40-60 Gy. RESULTS: Probability of overall survival was 80% at 6 months, 48% at 1 year, and 11% at 2 years. Median survival was 50 weeks. Univariate analysis showed that both tumor volume (T < or T > or = 30 cm(3)) and Karnofsky performance status score were significant predictors of survival. Multivariate analysis showed that smaller tumor volumes were associated with a higher probability of survival (p < 0.001). CONCLUSION: Tumor volume less than 30 cm(3) was associated with a higher probability of, and quality of, survival than larger lesions for patients reirradiated by brachytherapy for recurrent glioblastoma.     

Descriptive study of gallbladder,extrahepatic bile duct,and ampullary cancers in the United States, 1997–2002

OBJECTIVE: Few investigations of biliary tract (gallbladder, extrahepatic bile duct, ampulla of Vater) cancers have been conducted because of the relative rarity of these malignancies. The objective of this analysis was to compare the demographic, pathological, and clinical features of biliary tract cancers among men and women. METHODS: Biliary tract cancers among 11,261 men and 15,722 women were identified through 33 US population-based registries during the period 1997-2002. These registries were estimated to represent 61% of the US population. Age-adjusted incidence rates (AAIR) were calculated per 100,000 population using counts derived from the 2000 US census. RESULTS: The AAIR for gallbladder cancer among men (0.82 per 100,000) was significantly lower than the AAIR among women (1.45 per 100,000). By contrast, rates for extrahepatic bile duct and ampullary cancers were significantly higher among men (0.93 per 100,000 and 0.70 per 100,000, respectively) than among women (0.61 per 100,000 and 0.45 per 100,000, respectively). White men and women had significantly lower AAIRs for gallbladder cancer compared with other racial-ethnic groups, with the highest rates among Hispanics, American Indian-Alaska Natives, and Asian-Pacific Islanders. Asian-Pacific Islanders and Hispanics of both sexes had the highest AAIRs for extrahepatic bile duct and ampullary cancers. Ampullary tumors were more likely to be diagnosed at a localized or regional stage than were cancers of the gallbladder and extrahepatic bile duct. Asian-Pacific Islander men and women tended to have more unstaged cancers than other groups. CONCLUSIONS: This population-based study suggests distinct etiologies of anatomic subsites of biliary tract cancer and caution against analytic investigations of all biliary tract cancers combined.