Intraoperative electron boost radiation followed by moderate doses of external beam radiotherapy in limb-sparing treatment of patients with extremity soft-tissue sarcoma

PURPOSE: To analyze long-term prognosis and morbidity after limb-sparing treatment of patients with extremity soft-tissue sarcoma, with intraoperative electron boost radiotherapy (IOERT) followed by a moderate dose of external beam radiotherapy (EBRT). METHODS AND MATERIALS: A total of 153 patients who were treated in a single center from 1991 to 2004 were evaluated. Median IOERT dose was 15 Gy, mean EBRT dose 43 Gy (range, 40-50.4 Gy) in conventional fractionation (1.8-2 Gy). Median duration of follow-up was 33 months. Acute toxicity was assessed with Common Toxicity Criteria; late toxic effects were scored according to European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group criteria. RESULTS: Five-year overall survival and 5-year local control rates were 77% and 78%, respectively. Whereas tumor size, patient age, and EBRT dose did not significantly affect outcome, resection status and grading were significant for survival; resection status and IOERT dose were significant for local control. Extremity salvage until death or time of follow-up was achieved in 90% of our patients, 86% of whom showed excellent limb function without impairment in activities of daily life. Acute toxicity Grade 2-4 was observed in 23% and late toxicity Grade 2-4 in 17% of patients. CONCLUSIONS: Treatment with IOERT combined with moderate doses of external beam irradiation yields high local control and extremity preservation rates in resected extremity soft-tissue sarcoma.     

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.     

Patterns of failure and local control after intraoperative electron boost radiotherapy to the presacral space in combination with total mesorectal excision in patients with locally advanced rectal cancer

PURPOSE: To evaluate local control and patterns of failure in patients treated with intraoperative electron beam radiotherapy (IOERT) after total mesorectal excision (TME), to appraise the effectiveness of intraoperative target definition. METHODS AND MATERIALS: We analyzed the outcome of 243 patients with rectal cancer treated with IOERT (median dose, 10 Gy) after TME. Eighty-eight patients received neoadjuvant and 122 patients adjuvant external beam radiotherapy (EBRT) (median dose, 41.4 Gy), and in 88% simultaneous chemotherapy was applied. Median follow-up was 59 months. Results: Local failure was observed in 17 patients (7%), resulting in a 5-year local control rate of 92%. Only complete resection and absence of nodal involvement correlated positively with local control. Considering IOERT fields, seven infield recurrences were seen in the presacral space, resulting in a 5-year local control rate of 97%. The remaining local relapses were located as follows: retrovesical/retroprostatic (5), anastomotic site (2), promontorium (1), ileocecal (1), and perineal (1). CONCLUSION: Intraoperative electron beam radiotherapy as part of a multimodal treatment approach including TME is a highly effective regimen to prevent local failure. The presacral space remains the site of highest risk for local failure, but IOERT can decrease the percentage of relapses in this area.     

Intraoperative electron beam radiotherapy for previously irradiated advanced head and neck malignancies

Purpose: This is a retrospective review to evaluate the role of surgery and intraoperative electron beam radiotherapy (IOERT) in the treatment of patients with previously irradiated advanced head and neck cancers.

Methods and Materials: Between January 1992 and March 1997, 38 patients (31 males, 7 females; median age of 62 years) with recurrent head and neck cancer were treated with maximal resection and IOERT at the Ohio State University (OSU). All had been previously treated with full-course radiotherapy (median 65.1 Gy, range 50–74.4 Gy). Twenty-nine patients (76%) had previously undergone one or more surgical procedures. After maximal surgery the tumor bed was treated with IOERT (single field in 36 patients and 2 fields in 2 patients), most commonly with 6 MeV electrons (87%). The dose administered (at 90% isodose line) was 15 Gy for close or microscopically positive margins in 34 patients and 20 Gy for gross disease in 1 patient. Further external beam radiation therapy (EBRT) was not given.

Results: After a median follow-up of 30 months (range 8–39 months), 24 of the 38 patients (66%) recurred within the IOERT field. Median time to IOERT failure was 6 months (95% CI: 4.3–7.7). The 6-month, 1-, and 2-year control rates within the IOERT volume were 41%, 19%, and 13 %, respectively. Thirty of the 38 patients (79%) recurred in locoregional areas. Median time to locoregional failure was 4 months (95% CI: 3.3–4.7). The 6-month, 1-, and 2-year locoregional control rates were 33%, 11%, and 4%, respectively. Distant metastases ocurred in 7 patients, 5 in association with IOERT failure and 2 with locoregional failure. Median overall survival was 7 months (95% CI: 4.7–9.3). The 6-month, 1-, 2-, and 3-year actuarial survival rates were 51%, 21%, 21%, and 8%, respectively. Major treatment-related complications occurred in 6 patients (16%).

Conclusion: IOERT alone, at the dose used, is not sufficient for control of recurrent, previously irradiated head and neck cancers. Since higher IOERT doses are associated with high morbidity, we are currently evaluating the addition of limited EBRT dose and/or brachytherapy to improve the local control of these poor prognostic recurrent tumors, with acceptable morbidity.     

Outcomes in a series of 103 retroperitoneal sarcomas

AIMS: To report the effect on outcome of selection in patients receiving intra-operative electron beam radiation (IOERT) and external beam radiation therapy (EBRT). METHODS: One hundred and three patients treated for primary RS were studied. Median follow-up was 27 months. Clinical presentation, tumor characteristics, and treatment methods were analyzed to determine impact on survival and recurrence and if selection was occurring. RESULTS: Mean age was 55+/-17 years. Mean tumor size was 15+/-6cm and 88 were high-grade. Complete gross tumor resection (CR) occurred in 62 patients and improved survival vs. both debulking (p=0.0005) and biopsy (p<0.0001). The 5- and 10-year survival rates were 62% and 52% for those with CR vs. 29% and 20% after incomplete resection. Among the 62 CR patients, there was selection to receive additional EBRT+/-IOERT in patients with high-grade tumors (p=0.005) and/or microscopically positive margins (p=0.011). In these high-risk patients there was a trend for IOERT to further augment survival vs. EBRT alone and to increase the time to both local and distant recurrences (p=0.036). CONCLUSIONS: Complete gross resection is the primary form of curative treatment for retroperitoneal sarcomas. Selection led to patients with high-risk tumors receiving additional radiation therapy. There appears to be a beneficial effect of IOERT plus EBRT in these high-risk patients after complete tumor resection.     

Use of intraoperative electron beam radiotherapy in the management of retroperitoneal soft tissue sarcomas

PURPOSE: To evaluate the disease control, survival results, and tolerance of intraoperative electron beam radiotherapy (IOERT) as a component of treatment for retroperitoneal soft tissue sarcomas. METHODS AND MATERIALS: Between March 1981 and September 1995, 87 patients with primary (n = 43) or recurrent (n = 44) retroperitoneal or intrapelvic sarcomas received IOERT as a component of treatment at the Mayo Clinic. The tumors were high grade in 54 patients (62%) and low grade in 33 (38%). The median tumor size was 10 cm (range 2-36). All patients underwent maximal surgical resection with IOERT; in 72 patients, only microscopic or no residual tumor remained. The IOERT doses ranged from 8.75 to 30 Gy (median 15). All primary tumors received external beam irradiation (EBRT) with a median dose of 48.6 Gy. Thirty-four of the 44 recurrent tumors received EBRT to a median dose of 45 Gy. All patients were followed prospectively for outcome and toxicity evaluation. RESULTS: The median follow-up, based on 46 patients (53%) currently alive, was 3.5 years. The overall estimated 5-year survival was 47%. For patients with tumors > or = 10 cm, the 5-year overall survival was significantly poorer (28%) than for those with smaller lesions (60%) (p = 0.01). Neither primary vs. recurrent status nor tumor grade had a significant impact on survival. Patients with gross residual tumor had a marginally significantly poorer survival compared with patients with microscopic or no residual tumor, with a 5-year survival rate of 37% and 52%, respectively (p = 0.08). A total of 49 patients (56%) experienced failure, including 20 local recurrences (23%). The median time to failure was 2.3 years. Four recurrences were within the IOERT field, 3 within the IOERT and EBRT field, and 13 within the EBRT field alone. The 3- and 5-year estimated local control rate was 77% and 59%, respectively. Local control was marginally significantly affected by the amount of residual tumor, with a 5-year local control rate of 41% for those with gross residual tumor, 60% for those with microscopic residual tumor, and 100% for those with no residual tumor (p = 0.09). Gastrointestinal complications were recorded in 12 incidences (Grade 3 or higher toxicity). These complications were believed to be secondary to surgery and/or EBRT in 10 of the 12 cases. Seven patients had fistula formation, and 3 experienced severe proctitis. Grade 3 peripheral neurologic toxicities occurred in 9 patients (10%), but none had pain as a component of their neuropathy. CONCLUSION: Retroperitoneal soft tissue sarcomas can be treated with an aggressive combined approach of EBRT, surgery, and IOERT, with acceptable toxicity. Local control in primary disease appears to be improved in this retrospective series with this approach. Distant disease control and options for recurrent disease needs further definition.     

Intraoperative electron beam radiotherapy in recurrent colorectal carcinoma.

BACKGROUND AND OBJECTIVES: The installation of a dedicated linear accelerator in a shielded operating room in 1992 allowed us to start a feasibility study of intraoperative electron beam radiation therapy (IOERT) in colorectal carcinoma. METHODS: From March 1992 to February 1996, 28 patients with recurrent colorectal carcinoma were treated with maximal surgical resection and IOERT to the pelvis (n = 20) or paraortics (n = 8). IOERT dose ranged from 10 to 20 Gy with electron energies of 6-15 MeV. Postoperative external beam radiation therapy (EBRT) of 45-50 Gy was planned for the previously unirradiated patients. RESULTS: IOERT was well tolerated, but 10 (70%) of 13 patients in the previously unirradiated group did not complete the EBRT per protocol. Eight patients (29%) had some morbidity including surgically related fistula distal from IOERT sites. Two patients developed pelvic pain, which can be attributed to IOERT. Three-year local control at sites treated with IOERT was 40% (53% for previously irradiated patients and 27% for previously unirradiated patients). The 3-year actuarial overall survival was 12% (17% for previously irradiated patients and 8% for previously unirradiated patients). CONCLUSIONS: Our initial experience showed that it was feasible to treat poor prognostic colorectal cancer patients with IOERT. The morbidity observed was mainly related to extensive surgery in high-risk patients. Poor local control was obtained in patients treated with low-dose IOERT alone. Hence, previously unirradiated patients are encouraged to complete the planned EBRT or, alternatively, are considered for EBRT preoperatively or are given a higher IOERT dose (up to 20 Gy) if EBRT will not be given. Since IORT doses >20 Gy are associated with nerve toxicity, we currently add limited dose EBRT in the previously irradiated group. Patients with disease located in multiple abdominal sites are no longer considered candidates for IOERT.     

Long-term normal tissue effects of intraoperative electron radiation therapy (IOERT): late sequelae, tumor recurrence, and second malignancies

PURPOSE: To evaluate long-term survivors treated with intraoperative electron radiation therapy (IOERT) as a component, with particular emphasis on analyzing late normal tissue toxicity, second malignancies, and patterns of delayed tumor recurrence. METHODS AND MATERIALS: From September 1984 to December 1991, 739 patients were treated with IOERT. One hundred ninety-five patients were alive at least 5 years after IOERT (26%). Patient information regarding late complications related symptoms, incidence of second tumors, and delayed relapses were analyzed. Normal tissue changes were categorized by a modified LENT/SOMA scale (Grade 0-1, Grade 2, and Grade 3-4). Risk of late toxicity was grouped by type and number of cancer treatment modalities employed in each patient: surgery + IOERT alone (17 patients, 9%); IOERT + external radiotherapy +/- chemosensibilization (90 patients, 46%); IOERT +/- external radiotherapy +/- neoadjuvant chemotherapy (+/- previous radiotherapy) (88 patients, 45%). Biologic effective doses (BED) were calculated for alpha/beta = 3.5 for late fibrosis. RESULTS: With a mean follow-up time of the surviving patients of 94 months (range: 55-162 months), 99 patients (51%) had Grade 0-1 toxicity, 52 (27%) had Grade 2, and 44 patients (23%) presented Grade 3-4 late normal tissue complications. Risk groups by treatment intensity did correlate with severity of observed toxicity (p < 0.001). BED estimations did not correlate with late normal tissue damage. The tumor type with higher toxicity scores was bone sarcoma (28/46, 60%), in which the estimated BED = 100.5 Gy. Peripheral neuropathy was the dominant IOERT-specific toxicity present in 24 patients (12%). Second malignancies were identified in 8 patients (4%), none inside the IOERT field (3 questionable to be marginal to the external beam radiotherapy volume). In 36 patients (18%), recurrence of the originally treated tumor was detected, including 11 (7%) local relapses. CONCLUSIONS: The incidence of late normal tissue complications (50%) and severity (23%) is significant in a cohort of patients surviving more the 5 years after IOERT. The understanding of the contribution of IOERT to late tissue damage requires specific analysis. Peripheral neuropathy is a characteristic finding in IOERT trials. Second malignancies inside the IOERT field were not identified during the study period. The risk of recurrences, including local failures, requires an intensive follow-up of long-term survivors from IOERT trials.     

Intra-operative electron radiotherapy as a conservative treatment for infiltrating bladder cancer

The intent of this feasibility study was to evaluate the use of intra-operative electron radiotherapy (IOERT), after transurethral resection (TUR), combined with external beam radiation with concurrent chemotherapy for the conservative treatment of infiltrating bladder cancer. From November 1988 to June 1998, 27 patients with histologically proven non-metastatic infiltrating bladder cancer were included in this protocol. The treatment consisted of: TUR, external beam irradiation (x18 MV:48 Grays (Gy)/24 fractions/5 weeks), with concurrent chemotherapy (cisplatin 30 mg/day for 3 days-two cycles during irradiation), followed by control cystoscopy and cystotomy with IOERT (e 9 MeV:15 Gy). 14 patients received two cycles of neoadjuvant methotrexate, vinblastine and cisplatin (MVC) and folinic acid chemotherapy. Patients were evaluated for toxicity, local control and survival. The 5-year overall and cystectomy-free survival rates were 53.3% +/-11.1% and 48.1%+/-11.4%, respectively. 4 patients developed infiltrating intravesicular recurrence (3 were treated by salvage cystectomy), and an additional patient developed a superficial recurrence. 2 patients subsequently developed regional recurrence in pelvic nodes and 10 patients were found to have distant metastases. The protocol was found to be feasible and associated with acceptable toxicity. Early and late toxicities consisted of 3 cases of bladder mucosal necrosis or ureteral stenosis which resolved with medical management. These preliminary results indicate that IOERT combined with TUR and neoadjuvant external beam radiation with concurrent chemotherapy is feasible. It could be considered as an alternative therapy for infiltrating carcinoma of the bladder, especially in patients unfit for radical surgery, and is well adapted to treat lesions of the fixed portion of the bladder.     

Influence of site on the therapeutic ratio of adjuvant radiotherapy in soft-tissue sarcoma of the extremity

PURPOSE: The ultimate goal of adjuvant radiotherapy (RT) in soft-tissue sarcoma of the extremity is to improve the therapeutic ratio by increasing local control while minimizing morbidity. Most efforts in trying to improve this ratio have focused on the sequencing of RT and surgery, with little attention to the potential influence of the tumor site. The purpose of this study was to determine the influence of tumor site on local control and complications in a group of patients with primary high-grade soft-tissue sarcoma of the extremity treated at a single institution with postoperative RT. METHODS AND MATERIALS: Between July 1982 and December 2000, 369 adult patients with primary high-grade soft-tissue sarcoma of the extremity were treated with limb-sparing surgery and postoperative RT. Patients who underwent surgery or RT outside our institution were excluded. The tumor site was the upper extremity (UE) in 103 (28%) and the lower extremity (LE) in 266 (72%). The tumor was < or = 5 cm in 98 patients (27%), and the microscopic margins were positive in 44 (12%). Of the 369 patients, 104 (28%) underwent postoperative external beam RT (EBRT), 233 (63%) postoperative brachytherapy (BRT), and 32 underwent a combination (9%); 325 (88%) received a "conventional" radiation dose, defined as 60-70 Gy for EBRT, 45 Gy for BRT, and 45-50 Gy plus 15-20 Gy for EBRT plus BRT. Complications were assessed in terms of wound complications requiring repeat surgery, fracture, joint stiffness, edema, and Grade 3 or worse peripheral nerve damage. RESULTS: The UE and LE groups were balanced with regard to age, depth, margin status, and type of RT (EBRT vs. BRT +/- EBRT). However, more patients in the UE group had tumors < or = 5 cm and more received a conventional radiation dose (p = 0.01 and P = 0.03, respectively). With a median follow-up of 50 months, the 5-year actuarial rate of local control, distant relapse-free survival, and overall survival for the whole population was 82% (95% confidence interval [CI], 77-86%), 61% (95% CI, 56-66%), and 71% (95% CI, 66-76%), respectively. The 5-year local control rate in patients with UE STS was 70% (95% CI, 60-80%) compared with 86% (95% CI, 81-91%) for LE STS (p = 0.0004). On multivariate analysis, an UE site (p = 0.001; relative risk [RR], 3; 95% CI, 2-5) and positive resection margins (p = 0.02; RR, 2; 95% CI, 1-4) were significant predictors of poor local control. The RT type or radiation dose, age, tumor depth, and size were not significant predictors of local control. The 5-year wound reoperation rate was 1% (95% CI, 0-3) in the UE compared with 11% (95% CI, 7-15) in the LE (p = 0.002). On multivariate analysis, the UE site retained its significance as a predictor of low wound complications (p = 0.001; RR, 0.08; 95% CI, 0.01-0.7). The site did not significantly influence the incidence of fracture (p = 0.7), joint stiffness (p = 0.2), edema (p = 0.5), or Grade 3 or worse peripheral nerve damage (p = 0.3). CONCLUSION: The UE site is associated with a greater rate of local recurrence compared with the LE. This difference was independent of other variables and could not be accounted for by an imbalance between the two groups. With a lower wound complication rate associated with an UE site, it would be of interest to determine whether preoperative RT and/or intensity-modulated RT can increase the local control in UE sarcomas, thus improving the therapeutic ratio.     

Adjuvant radiation for stage II-B soft tissue sarcoma of the extremity.

PURPOSE: Adjuvant radiation therapy (RT) has been shown to improve local control in patients with high-grade soft tissue sarcoma (STS) of the extremity. This study sought to define the optimal management in patients with stage II-B (high-grade, size < or = 5 cm) tumors. PATIENTS AND METHODS: Between July 1982 and December 1998, 204 adult patients with primary stage II-B STS underwent limb-sparing surgery with negative microscopic margins. Eighty-eight patients (43%) received RT; 116 (57%) did not. The RT and no-RT groups were balanced with regard to age, site (upper v lower extremity), whether patients had prior unplanned excision, and location (central, i.e., shoulder/groin v non-central). The RT group had more deep tumors (P =.03). Adjuvant RT was delivered with brachytherapy in 60% and external-beam radiation in 40% of patients. RESULTS: With a median follow-up of 67 months, the 5-year local control, distant relapse-free survival, and disease-specific survival rates were 82%, 80%, and 88%, respectively. There was no significant difference in local control between the RT and no-RT groups (84% v 80%, respectively, P =.3). Tumor depth, site, and prior unplanned excision did not correlate with local control. The only independent predictors of poor local control were central tumor location (relative risk [RR] = 3; 95% confidence interval [CI], 2 to 7; P =.005) and age more than 50 years (RR = 6; 95% CI, 2 to 13; P =.001). CONCLUSION: In this retrospective study, adjuvant RT did not significantly improve local control in patients with stage II-B STS of the extremity. The outcome of patients with central tumor location was poor, and efforts to identify the optimal local treatment approach for such patients are warranted.     

Intraoperative electron-beam radiotherapy and ureteral obstruction

PURPOSE: To quantify the risk of ureteral obstruction (UO) after intraoperative electron-beam radiotherapy (IOERT). METHODS AND MATERIALS: One hundred forty-six patients received IOERT of 7.5 to 30 Gy to 168 ureters; 132 patients received external radiotherapy. RESULTS: Follow-up ranged from 0.01 to 19.1 years (median, 2.1 years). The rates of clinically apparent type 1 UO (UO from any cause) after IOERT at 2, 5, and 10 years were 47%, 63%, and 79%, respectively. The rates of clinically apparent type 2 UO (UO occurring at least 1 month after IOERT, excluding UO caused by tumor or abscess and patients with stents) at 2, 5, and 10 years were 27%, 47%, and 70%, respectively. Multivariate analysis revealed that the presence of UO before IOERT (p < 0.001) was associated with an increased risk of clinically apparent type 1 UO. Increasing IOERT dose (p < 0.04) was associated with an increased risk of clinically apparent type 2 UO. UO rates in ureters not receiving IOERT at 2, 5, and 10 years were 19%, 19%, and 51%, respectively. CONCLUSIONS: Risk of UO after IOERT increases with dose. However, UO risk for ureters not receiving IOERT was also high, which suggests an underlying risk of ureteral injury from other causes.     

Neural stem cell-preserving external-beam radiotherapy of central nervous system malignancies

PURPOSE: Recent discoveries have implicated neural stem cells (NSC) as the source of plasticity and repair in the mature mammalian brain. Treatment-induced NSC dysfunction may lead to observed toxicity. This study evaluates the feasibility of NSC-preserving external beam radiotherapy. METHODS AND MATERIALS: A single computed tomography (CT) dataset depicting a right periventricular lesion was used in this study as this location reflects the most problematic geometric arrangement with respect to NSC preservation. Conventional and NSC preserving radiotherapy (RT) plans were generated for the same lesion using two clinical scenarios: cerebral metastatic disease and primary high-grade glioma. Disease-specific target volumes were used. Metastatic disease was conventionally treated with whole-brain radiotherapy (WBRT) to 3,750 cGy (15 fractions) followed by a single stereotactic radiosurgery (SRS) boost of 1,800 cGy to gross disease only. High-grade glioma was treated with conventional opposed lateral and anterior superior oblique beams to 4,600 cGy (23 fractions) followed by a 1,400 cGy (7 fractions) boost. NSC preservation was achieved in both scenarios with inverse-planned intensity modulated radiotherapy (IMRT). RESULTS: Cumulative dose reductions of 65% (metastatic disease) and 25% (high-grade glioma) to the total volume of the intracranial NSC compartments were achieved with NSC-preserving IMRT plans. The reduction of entry and exit dose to NSC niches located contralateral to the target contributed most to NSC preservation. CONCLUSIONS: Neural stem cells preservation with current external beam radiotherapy techniques is achievable in context of both metastatic brain disease and high-grade glioma, even when the target is located adjacent to a stem cell compartment. Further investigation with clinical trials is warranted to evaluate whether NSC preservation will result in reduced toxicity.     

肢体软组织肉瘤术后放疗缩小放疗野的临床观察

目的 探讨肢体软组织肉瘤术后缩小放疗野放疗的效果,重点观察局部控制率和不良反应发生情况。方法 回顾性分析2017年10月至2021年3月清华大学第一附属医院收治的49例肢体软组织肉瘤患者,所有患者术后均接受调强放疗。采用定位CT和术后MRI图像融合的方法进行靶区勾画,定义瘤床（GTV_tb）在纵轴方向外扩3 cm,横轴方向外扩1.5 cm形成临床靶区（CTV,解剖屏障可适当修回,且需包全肿瘤周围水肿区）。GTV_tb和CTV分别外扩0.5 cm形成计划靶区1（PTV1）和PTV2,放疗处方剂量：PTV1_95%为63~66 Gy,PTV2_95%为50~56 Gy,单次1.8~2.0 Gy。若术后镜下切缘阳性,瘤床区域推量至70 Gy。结果 随访7.9~45.6个月,中位随访时间32.1个月。3年无局部失败生存率、总生存率和无远处转移生存率分别为91.7%、77.6%、71.5%。单因素分析结果显示,术后镜下切缘阳性的患者更容易出现局部复发,P<0.05。2级及以上伤口并发症、关节僵硬、骨折、水肿、皮肤纤维化的发生率分别为2%、4.1%、2%、8.2%、26.5%。结论 术后放疗缩小放射野治疗肢体软组织肉瘤得到了较好的局部控制率,且晚期不良反应发生率较低。     

肢体软组织肉瘤术后放疗缩小放疗野的临床观察

目的 探讨肢体软组织肉瘤术后缩小放疗野放疗的效果,重点观察局部控制率和不良反应发生情况。方法 回顾性分析2017年10月至2021年3月清华大学第一附属医院收治的49例肢体软组织肉瘤患者,所有患者术后均接受调强放疗。采用定位CT和术后MRI图像融合的方法进行靶区勾画,定义瘤床（GTV_tb）在纵轴方向外扩3 cm,横轴方向外扩1.5 cm形成临床靶区（CTV,解剖屏障可适当修回,且需包全肿瘤周围水肿区）。GTV_tb和CTV分别外扩0.5 cm形成计划靶区1（PTV1）和PTV2,放疗处方剂量：PTV1_95%为63~66 Gy,PTV2_95%为50~56 Gy,单次1.8~2.0 Gy。若术后镜下切缘阳性,瘤床区域推量至70 Gy。结果 随访7.9~45.6个月,中位随访时间32.1个月。3年无局部失败生存率、总生存率和无远处转移生存率分别为91.7%、77.6%、71.5%。单因素分析结果显示,术后镜下切缘阳性的患者更容易出现局部复发,P<0.05。2级及以上伤口并发症、关节僵硬、骨折、水肿、皮肤纤维化的发生率分别为2%、4.1%、2%、8.2%、26.5%。结论 术后放疗缩小放射野治疗肢体软组织肉瘤得到了较好的局部控制率,且晚期不良反应发生率较低。     

Long-term outcomes after function-sparing surgery without radiotherapy for soft tissue sarcoma of the extremities and trunk.

PURPOSE: To define the rate of local recurrence (LR) and identify prognostic factors for LR for patients with soft tissue sarcoma (STS) treated with function-sparing surgery (FSS) without radiotherapy (RT). PATIENTS AND METHODS: Between 1970 and 1994, 242 patients with STS of the trunk and extremity presented with primary localized disease, 74 of whom were treated with FSS without RT (31%). The median tumor size was 4 cm (range, 0.5 to 31 cm). There were 40 patients with grade 1 tumors and 34 with grade 2 and 3 tumors. Median follow-up was 126 months. RESULTS: The 10-year actuarial local control rate was 93% +/- 4%. Resection margin status was a significant predictor for LR. Patients with closest histologic resection margins of less than 1 cm had a 10-year local control rate of 87% +/- 6% compared with 100% for patients with closest histologic resection margins of >/= 1 cm (P =.04). There was no significant association between LR and tumor grade, size, site (truncal v extremity), or depth (superficial v deep). For all patients, the 10-year actuarial survival rate was 73% +/- 6%. CONCLUSION: The 7% LR rate after treatment of STS with FSS without RT reported herein is comparable to published rates following treatment where adjuvant RT is used. These results suggest there may be a select subset of patients with STS in whom carefully performed FSS may serve as definitive therapy and in whom adjuvant RT may not be necessary. However, further study is needed to carefully define this subset of patients and to identify the optimal surgical approach and technique for patients treated without RT.     

Clinical significance of margin status in postoperative radiotherapy for extremity and truncal soft-tissue sarcoma

PURPOSE: To evaluate whether adjuvant radiotherapy (RT) in extremity and truncal soft-tissue sarcoma (STS) patients with microscopically positive or close margins after excision can achieve comparable local control to that of excision with negative margin plus RT. METHODS AND MATERIALS: A total of 150 patients (111 extremity and 39 trunk cases) treated with conserving surgery and adjuvant RT was analyzed. All surgical margins were classified as being a negative margin or a positive or close margin based on pathologic margin width. RT was delivered with a shrinking-field technique in 150 patients (median, 63 Gy). RESULTS: All patients were divided into two groups: (A) excision with negative margins plus RT (n = 56) and (B) excision with positive or close margins plus RT (n = 94). Overall, the 5-year local failure-free survival in all patients was 72.9%, and no significant differences were found between the two groups (Group A, 74.7%; Group B, 71.6%). High tumor grade was found to be a significant predictor of local failure. However, Group A was superior to Group B in distant metastasis-free survival (p = 0.02). No significant differences were shown in overall survival between the two groups. CONCLUSIONS: In our series, margin status did not predict for LF when adjuvant RT was used. We believe that when adjuvant RT is used, re-resection may not be necessary for selected patients with positive or close pathologic margins in the management of extremity and truncal STS patients.     

Combination of external-beam radiotherapy with intraoperative electron-beam therapy is effective in incompletely resected pediatric malignancies

PURPOSE: Intraoperative electron-beam radiotherapy (IOERT) has been applied for local dose escalation in over 1,400 patients in Heidelberg since 1991. Among these were 30 children, in 18 of whom IOERT was employed in radiation treatment with external-beam radiotherapy (EBRT) on account of incomplete resection. We address the question whether IOERT is able to compensate for microscopic or macroscopic tumor residue if employed in the overall radiation regimen. METHODS AND MATERIALS: The data of the aforementioned 18 children were analyzed with regard to local recurrence, overall survival, and complication rates. All children suffered from either sarcomas or neuroblastomas. In all children, IOERT was employed for local dose escalation after or before EBRT. RESULTS: After a median follow-up of 60.5 months, 15 of the treated children are alive. One local failure has been observed. Six children show clinically significant late morbidity, including the loss of a treated limb (Radiation Therapy Oncology Group Grade 4 [RTOG 4]), a severe nerve lesion (RTOG 3), an orthopedic complication (RTOG 2), a ureteral stenosis (not clinically significant), and a kidney hypotrophy (not clinically significant). In 1 child a fracture due to radionecrosis (RTOG 4) was diagnosed; however, in the follow-up, local tumor relapse was diagnosed as another possible reason for the fracture. CONCLUSIONS: Regarding the low incidence of local failure, IOERT seems to be able to compensate incomplete tumor resection in childhood sarcoma and neuroblastoma patients. The incidence of late morbidity is low enough to justify the employment of IOERT as part of the radiation treatment regimen for pediatric patients.     

Long-term outcome of patients with American Joint Committee on Cancer stage IIB extremity soft tissue sarcomas.

PURPOSE: It has been suggested that patients with small (< 5 cm), high-grade extremity soft tissue sarcomas (STS) have an excellent overall prognosis and, consequently, may not require adjuvant therapies. PATIENTS AND METHODS: A comprehensive review of all patients with extremity STS treated at a tertiary care cancer hospital over a 9-year period (January 1984 to December 1992) was performed. Prognostic factors, treatment data, and long-term outcome were evaluated in the subset of 111 patients with American Joint Committee on Cancer stage IIB (G3/4, T1a/b) disease. RESULTS: The median tumor size was 3.0 cm (range, 0.6 to 4.9 cm), and 55 tumors (50%) were deep in location. All patients underwent surgical resection; 68 (61%) received pre- or postoperative radiotherapy, and 32 (29%) received doxorubicin-based chemotherapy. The median follow-up was 76 months. Forty patients (36%) experienced 59 recurrences. First recurrences occurred at local, regional, and distant sites in 21, five, and 14 patients, respectively. The 5-year actuarial local recurrence-free, distant recurrence-free, disease-free, and overall survival rates were 82%, 83%, 68%, and 83%, respectively. The presence of a microscopically positive surgical margin was an independent adverse prognostic factor for both local recurrence (relative risk [RR] = 3.75; 95% confidence interval [CI], 1.25 to 11.25; P =.02) and disease-free survival (RR = 2.57; 95% CI, 1.33 to 4.98; P =.005). CONCLUSION: Event-free outcome for this subset of patients with high-grade STS does not seem as favorable as previously reported by other investigators. Patients who undergo maximal surgical resection with microscopically positive margins represent a subset of T1 STS patients who warrant consideration for adjuvant therapies.     

Local control comparison of adjuvant brachytherapy to intensity-modulated radiotherapy in primary high-grade sarcoma of the extremity

BACKGROUND:

Based on results of a prospective randomized trial, brachytherapy (BRT) had been the preferred form of adjuvant radiotherapy for patients with high‐grade extremity soft tissue sarcoma (STS) at our institution. In recent years, intensity‐modulated radiotherapy IMRT had been increasingly used. This study compared local control by IMRT versus by BRT in primary‐extremity STS.

METHODS:

Between January 1995 and December 2006, 134 adult patients with high‐grade primary nonmetastatic STS of the extremity were treated at this institution with limb‐sparing surgery and adjuvant radiotherapy (RT). Low‐dose‐rate BRT was given to 71 patients between January 1995 and November 2003 to a median dose of 45 Gray (Gy). IMRT was given between February 2002 and December 2006: preoperatively to 10 (50 Gy) and postoperatively to 53 (median, 63 Gy). Median follow‐up was 46 months.

RESULTS:

Treatment groups were comparable in terms of gender, age, site, depth, histology (malignant fibrous histiocytoma vs other), and use of adjuvant chemotherapy. More IMRT patients had positive/close margins (<1 mm), large tumors (>10 cm), and bone or nerve stripping/resection (P = 0.006, 0.005, 0.02, and 0.002, respectively). Median follow‐up was 46 months for IMRT and 47 months for BRT. Five‐year local control was 92% (95% confidence interval [CI], 85‐100) for IMRT versus 81% (95% CI, 71‐90) for BRT, P = 0.04. On multivariate analysis, IMRT was the only predictor of improved local control, P = 0.04.

CONCLUSIONS:

Local control with IMRT was significantly better than BRT despite higher rates of adverse features for IMRT in this nonrandomized comparison. IMRT should be further examined as the treatment of choice for primary high‐grade extremity sarcoma. Cancer 2011. © 2011 American Cancer Society.