Perioperative hyperfractionated high-dose rate brachytherapy combined with external beam radiotherapy in the treatment of soft tissue sarcomas

AIMS AND BACKGROUND: Low-dose rate brachytherapy alone or in combination with external beam radiotherapy represents a well-established adjuvant treatment in soft tissue sarcomas following surgical resection. The experience with high-dose radiotherapy in this indication is limited. The purpose of our study was an evaluation of the viability of perioperative hyperfractionated high-dose rate brachytherapy in combination with external beam radiotherapy for primary and recurrent soft tissue sarcomas. PATIENTS AND METHODS: From February 1998 through June 2002, 10 adult patients with soft tissue sarcomas were treated by interstitial perioperative high-dose rate brachytherapy and external beam radiotherapy. TNM classification was pT2bpN0pM0 in 9 patients and pT1bpN0pM0 in 1 patient. Grade of differentiation was G1 (2 patients), G2 (n = 1), G3 (n = 5), G4 (n = 2). Surgical margins were negative in 7 cases, close in 2 cases and positive in 1 case. The tumor was localized in an extremity in all cases. Hyperfractionation 3 Gy twice daily at 10 mm from the plane of sources was used for brachytherapy, with total doses 18-30 Gy. The patients received external beam radiotherapy with doses 40-50 Gy after brachytherapy. Follow-up periods were between 24-71 months (median, 46). RESULTS: Local control of the disease was achieved in all 10 patients. Distant metastases occurred in 2 cases. One patient was disease free after salvage surgery and chemotherapy, and one patient died of lung disease progression 14 months after brachytherapy. In one case, subcutaneous fistula occurred after radiotherapy and was cured by an excision. Six patients experienced grade 1 or 2 fibrosis and 1 case a mild peripheral neuropathy was recorded. CONCLUSIONS: Our study on a small number of patients suggests that perioperative hyperfractionated high-dose rate brachytherapy with doses 8 x 3 Gy in combination with external beam radiotherapy 40-50 Gy is a promising method to achieve high biological doses in the postoperative radiotherapy of soft tissue sarcomas without severe late morbidity and warrants further research.     

Neoadjuvant chemotherapy and combined conservative treatment of soft tissue sarcoma in the adult]

Between 1980 and 1990, 64 adults with a locally advanced soft tissue sarcoma, but without metastasis, were treated with neoadjuvant chemotherapy before conservative local treatment. Tumour localizations were limbs in 26 patients (40.6%) and other parts of the body in 38 patients (59.4%). Moreover, 27 patients had bone and/or vasculo-nervous axis involvement. Response to chemotherapy was > or = 50% for 23 patients (37.7%) with 3 complete remissions, < 50% for 36 patients and only 2 tumours progressed during chemotherapy. Conservative surgery was thus carried out for 51 patients (79.7%), 11 received external radiotherapy only. At the end of treatment, 49 patients (76.5%) were in complete remission. With a median follow-up of 76 months (range: 25 to 147), 25 patients are alive with no evolutive disease. For the whole population, the actuarial 5-year overall survival is 33.8%. Among the patients who were in complete remission at the end of therapy, 15 developed local recurrences (with metastasis for 7 patients) and 10 became metastatic. Actuarial 5-year overall survival for this subset of patients is 44.8%.     

术中置管近距离放疗在骨与软组织肉瘤治疗中的应用

目的分析术中置管近距离放疗在骨与软组织肉瘤综合治疗中应用的疗效和毒性。方法163例骨与软组织肉瘤的病例，其中59例采用手术＋化疗＋外照射，另外104例采用手术＋化疗＋近距离放疗＋夕h照射的综合治疗方法。结果采用近距离放疗的一组患者有较好的疗效和较低的毒性。结论术中置管近距离放疗在骨与软组织肉瘤的综合治疗中有较好临床应用价值．．     

Soft tissue sarcoma. Integration of brachytherapy, resection, and external irradiation

Between December 1981 and August 1988, 63 patients with clinically localized nonretroperitoneal soft tissue sarcomas underwent 65 brachytherapy procedures in conjunction with conservative resection with (61 tumors) or without (four tumors) external beam irradiation. Implant doses of 1500 to 2000 cGy were combined with 4500 to 5000 cGy of external irradiation. External irradiation was given preoperatively for larger lesions near bone or neurovascular structures, whereas it was used postoperatively for smaller, more resectable lesions or those that had previously been inadequately excised. There were 47 high-grade tumors, 34 tumors greater than 5 cm, and nine patients with recurrent lesions (five with previous irradiation). With mean follow-up of 20 months, conclusions on local control are tentative, but only two of 56 tumors (4%) with brachytherapy as part of initial management had recurred locally and three of nine recurrent tumors had re-recurred locally. Only one of five local recurrences was within the implanted volume. Only two of 40 implantations (5%) performed at initial resection followed by postoperative external irradiation led to wound complications, whereas four of 16 implantations (25%) performed at resection after preoperative external irradiation were associated with wound problems. This technique does not increase local morbidity and may enhance local tumor control in comparison with either external radiation or brachytherapy alone as an adjuvant to conservative resection.     

异环磷酰胺联合表阿霉素治疗晚期软组织肉瘤27例疗效分析

目的观察异环磷酰胺（IFO）联合表阿霉素（EPI）方案治疗晚期软组织肉瘤（ASTS）的疗效与安全性。方法采用IFO＋EPI方案治疗ASTS 27例。IFO 6g/m^2,分d1～3静脉滴入或96 h持续静脉点滴;EPI 90 mg/m^2,分d1～3（或96 h持续静脉点滴）,21 d为1个周期。本组中位化疗周期数为3个（2～5个）。结果CR 0例,PR 5例,SD 13例,PD 9例,全组总有效率18.5%,临床获益率为66.7%,1年生存率为37.0%,2年生存率为11.1%。其中5例PR患者均为一线治疗,一线治疗有效率为23.8%（5/21）。主要毒性反应为骨髓抑制及胃肠道反应。结论EPI联合IFO治疗ASTS,使用方便、疗效确切、毒性反应较轻,该方案是ASTS有效解救治疗方案。     

Limb salvage surgery in combination with brachytherapy and external beam radiation for high-grade soft tissue sarcomas

While combined treatment of high-grade soft tissue sarcoma with resection and radiotherapy has become an accepted standard, outlines of treatment algorithms remain a matter of debate. Our institutional practice foresees wide surgical resection with adjuvant brachytherapy and external beam radiation. It was the purpose of this study to determine long-term outcome, prognostic factors for local and systemic recurrence and morbidity in patients with high-grade soft tissue sarcomas of the extremities, who were subjected to this regimen.     

Current results of brachytherapy for soft tissue sarcoma

Perioperative brachytherapy results in a better local control rate than surgery alone for extremity soft tissue sarcoma. Brachytherapy enables the delivery of a high radiation dose to a limited volume of tissue, allows the reduction of radiation treatment time, enables direct visualization of the tumor bed and surrounding critical structures, and costs less than external beam radiotherapy. The literature seems to regard the effectiveness of brachytherapy as comparable to that of external beam radiotherapy, and the side effect profile is acceptable. Traditional low-dose-rate brachytherapy methods require extended periods of patient isolation, but recent technologic advances may obviate this necessity. Newer high-dose-rate (HDR) brachytherapy delivery methods allow for the fractionation of radiation delivery and outpatient treatment in some cases. Furthermore, with HDR brachytherapy, the radiation dose distribution can be tailored around critical anatomic structures. Although the application of HDR brachytherapy to soft tissue sarcoma is relatively new, it seems to result in a satisfactory local control rate and may replace traditional low-dose-rate techniques.     

Local recurrence of soft tissue sarcoma following brachytherapy

Twenty-five patients with soft tissue sarcomas were treated with Ir192 implants following wide local excision at our institution between 1982 and 1987. External beam radiotherapy was given in addition to the implant in a majority of patients. The median follow-up in these 25 patients is 36 months (12 to 75 months). Twenty patients have had no evidence of local recurrence following their primary treatment (FFR = 80%). A multivariate analysis using stepwise logistic regression was used to predict failure in 3 years or less. Potential predictors examined included age, sex, tumor location, primary versus recurrent disease, grade, histology, surgical margins, implant only versus implant plus external beam, and a ratio of the volume of tissue which received 65 Gy (TV65) to the tumor volume (TV), that is (TV65/TV). The single variable which was significantly associated with local failure by 3 years was a TV65/TV of less than one. Once this variable was entered into the analysis, no other factor proved statistically significant. Our data suggest that when attempting local control of soft tissue sarcomas with brachytherapy, the volume of tissue receiving 65 Gy (TV65) from both implant and external beam must exceed the volume of the excised lesion (TV). Since the volume of a tumor can be readily determined prior to surgical excision either by CT or MRI scanning, pre-planning of the implant volume could potentially reduce the rate of local failure.     

Perioperative irradiation in extremity soft tissue sarcoma

Adjuvant radiotherapy constitutes an important component of the treatment of soft tissue sarcomas. Extremity soft tissue sarcomas constitute a large proportion of this rare mesenchymal tumor. Questions regarding timing, techniques and toxicity come into play about optimizing adjuvant radiotherapy. This article will discuss recent trends and outcomes of perioperative, that is, preoperative and postoperative, irradiation.     

3D conformal HDR brachytherapy and external beam irradiation combined with temporary androgen deprivation in the treatment of localized prostate cancer.

PURPOSE: To evaluate treatment outcome of 3D conformal high dose rate (HDR) brachytherapy and external beam irradiation (EBRT) combined with temporary androgen deprivation for patients with localized prostate cancer. PATIENTS AND METHODS: Between January 1997 and September 1999 we treated 102 patients with stage T1-3 N0 M0 prostate cancer. Stage T1-2 was found in 71, T3 in 31 patients. Median pretreatment PSA level was 15.3 ng/ml. After ultrasound-guided transrectal implantation of four afterloading needles, CT based 3D brachytherapy planning was performed. All patients received four HDR implants using a reference dose per implant of 5 or 7Gy. Time between each implant was 14 days. After brachytherapy EBRT followed up to 39.6 or 45.0 Gy. All patients received temporary androgen deprivation, starting 2-19 months before brachytherapy, ending 3 months after EBRT. RESULTS: Median follow-up was 2.6 years (range 2.0-4.1 years). Actuarial biochemical control rate was 87% at 2 years and 82% at 3 years. In 14 patients we noted biochemical failure, in five patients clinical failure. Overall survival was 90%, disease specific survival 98.0% at 3 years. Acute grade 3 toxicity occurred in 4%, late grade 3 toxicity in 5%. One patient developed a prostatourethral-rectal fistula as late grade 4 toxicity. The conformal quality of 300 HDR implants was analyzed using dose volume histograms. CONCLUSIONS: 3D conformal HDR brachytherapy and EBRT combined with temporary androgen deprivation is an effective treatment modality for prostate cancer with minimal associated toxicity and encouraging biochemical control rates after a median follow-up of 2.6 years.     

手术切除联合术中放疗治疗四肢复发性软组织肉瘤的安全性及近期疗效

目的:探讨手术切除联合术中放疗治疗四肢复发性软组织肉瘤的安全性及近期疗效。方法:收集2012年1月至2018年6月于我院诊断为四肢复发性软组织肉瘤并行手术切除的患者,共93例,根据患者放疗方案分为术中放疗组（38例）和体外放疗组（55例）。采用Log-rank单因素和Cox比例风险模型分析患者局部无复发生存期和总生存期的独立危险因素,并对两组术后并发症、急慢性放射性损伤、肢体功能等指标进行对比。结果:复发性软组织肉瘤局部无复发生存时间和总体生存时间与AJCC分期（P=0.030和P=0.012）和 FNCLCC分级（P=0.024和P=0.008）有关,术中放疗组与体外放疗组局部无复发生存期和总体生存时间没有明显统计学差异（P=0.663和P=0.691）。FNCLCC分级显著影响局部无复发生存期（HR=2.461,95%CI 1.094~5.537,P=0.029）和总生存期（HR=2.731,95%CI 1.249~5.971,P=0.012）。两组术后Clavien-Dindo并发症分级（P=0.048）、急性放射性损伤（P=0.043）、慢性放射性损伤（P＜0.001）以及肢体功能评分（P＜0.001）差异均有统计学意义。结论:手术切除联合术中放疗治疗四肢复发性软组织肉瘤具有较好的近期疗效及安全性。     

Long-term results of intraoperative electron beam radiotherapy for primary and recurrent retroperitoneal soft tissue sarcoma

PURPOSE: This study assesses the long-term outcome of patients with retroperitoneal sarcoma treated by preoperative external beam radiotherapy, resection, and intraoperative electron beam radiation (IOERT). METHODS AND MATERIALS: From 1980 to 1996, 37 patients were treated with curative intent for primary or recurrent retroperitoneal soft tissue sarcoma. All patients underwent external beam radiotherapy with a median dose of 45 Gy. This was followed by laparotomy, resection, and IOERT, if feasible. Twenty patients received 10-20 Gy of IOERT with 9-15 MeV electrons. These patients were compared to a group of 17 patients receiving preoperative irradiation without IOERT. RESULTS: The 5-yr actuarial overall survival (OS), disease-free survival, local control (LC), and freedom from distant disease of all 37 patients was 50%, 38%, 59%, and 54%, respectively. After preoperative irradiation, 29 patients (78%) underwent gross total resection. For 16 patients undergoing gross total resection and IOERT, OS and LC were 74% and 83%, respectively. In contrast, these results were less satisfactory for 13 patients undergoing gross total resection without IOERT. For these patients, OS and LC were 30% and 61%, respectively. Four patients experienced treatment-related morbidity. CONCLUSIONS: In selected patients, IOERT results in excellent local control and disease-free survival with acceptable morbidity.     

Endobronchial brachytherapy in combination with external beam irradiation in obstructing malignant bronchial tumors

Endobronchial brachytherapy is commonly used in the palliative management of malignant airway obstructions. In the present study, we describe the results of brachytherapy (mean dose of 18 Gy), used in combination with external beam irradiation (mean dose of 50 Gy) in 30 patients who had primary bronchogenic carcinoma of the lung. The extent of airway obstruction was determined according to symptoms and by bronchoscopy. We found symptoms improved in nearly 37% of patients and 21 of 30 patients (70%), evaluated with bronchoscopy, showed a response when evaluated 3 to 6 months after brachytherapy. This endobronchial technique appeared to be a well-tolerated procedure with a low rate of acute toxicity. The immediate complication rate was 13%, during the follow-up 3 deaths were related to treatment, of which 2 were fatal haemoptysis (12 and 18 months after irradiation). We conclude that the combination of endobronchial brachytherapy with external beam irradiation may be useful and needs further comparisons with other irradiation procedures.     

Preoperative, intraoperative, and postoperative radiation in the treatment of primary soft tissue sarcoma

The rationale for combining radiation with conservative surgery in the treatment of sarcoma of soft tissue is discussed, as well as the advantages for performing the radiation preoperatively on the one hand and postoperatively on the other. The results of treatment of soft tissue sarcoma by radical resectional surgery or amputation in 464 patients at four centers and by conservative surgery, and postoperative radiation in 416 patients at three centers, have been reviewed. The local failure rates were 18.1% and 18.3%, respectively. The results obtained by radiation administered postoperatively (110 patients) or preoperatively (60 patients) at the Massachusetts General Hospital during the period September 1971 to August 1982 are analyzed and discussed with reference to 5-year actuarial local control and survival results as well as causes of failure with respect to AJC stage, histologic type, anatomic site, and size of tumor. The results which have been obtained by the preoperative approach are judged to be superior, particularly for the larger lesions and higher grades that predominated in that group. Of a total of 170 patients, there were 19 local failures; 13 of these were diagnosed at the time when metastatic disease was not evident. Of those 13, 12 have been subjected to salvage surgery and 7 remain with no evidence of disease at 1 to 3.5 years after the salvage procedure. A major problem in the management of these patients remains the occult metastatic disease.     

Flap reconstruction and interstitial brachytherapy in nonextremity soft tissue sarcoma

Radiotherapy is an integral component of management of high-grade soft tissue sarcomas. Interstitial brachytherapy is used to deliver a boost or radical dose with several advantages over external beam radiotherapy. There has always been a concern to use brachytherapy with flap reconstruction of skin defects after wide excision. We preset our initial experience with interstitial brachytherapy in two patients of recurrent high-grade non-extremity sarcomas treated with surgical excision and soft tissue reconstruction of surgical defect.     

外照射结合锎-252中子腔内照射治疗食管癌的临床观察

观察锎252(252cf)中子腔内照射结合外照射治疗食管癌的疗效,对70例食管癌患者每周予以252cf中子4Gy腔内照射1次,共4次。中子治疗后第2天予以60Co外照射,食管靶区每次剂量2Gy,4次/周,总剂量50～56Gy。近期疗效CR61例,PR8例,NR1例;1、3和5年生存率分别为75.7%、28.9%和22.5%。并发症发生率放射性食管炎48.6%、食管溃疡7.1%、食管狭窄25.7%和食管瘘2.9%。初步研究结果提示,外照射加252cf中子腔内照射治疗食管癌的疗效较理想,有一定的应用前景。     

Low-dose intraoperative brachytherapy in soft tissue sarcomas involving neurovascular structure.

BACKGROUND AND PURPOSE: To evaluate intraoperative brachytherapy in the management of soft tissue sarcomas involving neurovascular structures, its impact on local control and complications. PATIENTS AND METHODS: Between 01/1989 and 12/2002, 98 patients received an intraoperative implant in conjunction with conservative surgery. Brachytherapy was part of the initial treatment (79 cases) or performed in recurrent disease (19 cases). We studied primary sarcomas involving neurovascular structures treated with conservative surgery and intraoperative brachytherapy (n = 6) or intraoperative brachytherapy and external irradiation (n = 73). Conservative surgery was performed as first treatment (51 cases), after chemotherapy (21 cases) and after primary external radiation (seven cases). Brachytherapy was performed according to Paris system rules. Patients were loaded with Iridium 192 (64 cases) or connected to a Microselectron PDR (15 cases). Mean dose given by brachytherapy was 20 Gy. Mean dose given of external radiotherapy was 46 Gy. RESULTS: With a median follow-up of 58 months, 5-year actuarial survival was 69% and local free disease at 5 years was 90%. Acute side-effects occurred in 22/79 requiring surgical repair in 10 patients. Late side-effects occurred in 35/79. No patient required amputation for complications. Prognostic factors were studied for the occurrence of acute and late side-effects and local control. CONCLUSIONS: Intraoperative brachytherapy is efficient with excellent local control rates in soft tissue sarcomas presenting with neurovascular involvement and offers an acceptable conservative option.     

软组织肉瘤手术加术中放疗的临床研究

目的：探讨软组织肉瘤术中放疗的意义。方法：对39例软组织肉瘤患者行根治或姑息性手术，术中放疗在术中放疗手术室进行，术中根据肿瘤大小，选择不同术中放疗限光筒及6～12MeV电子线1次照射15～25Gy，姑息手术者剂量加大至36Gy。术后辅以外照射治疗，常规设野，5／周，2Gy／次，总量40～50Gy。初发病灶10例，术后复发29例。结果：39例患者随访12～64个月，3、5年局控率分别为71．8％和64．1％。3年生存率为82．0％。结论：术中放疗具有较高的局控率，比之其他治疗具有许多优点，将获得较高的生存率。