Intraoperative Electron Beam Radiotherapy Research Articles

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

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. 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. 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. 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.

Intraoperative electron-beam radiotherapy and ureteral obstruction

To quantify the risk of ureteral obstruction (UO) after intraoperative electron-beam radiotherapy (IOERT). One hundred forty-six patients received IOERT of 7.5 to 30 Gy to 168 ureters; 132 patients received external radiotherapy. 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. 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.

Intraoperative electron beam radiotherapy (ELIOT) to the breast: A need for a quality assurance programme

Intraoperative radiotherapy (IORT) is a technique in which a high, single-fraction radiation dose is delivered directly to the tumour bed during a surgical intervention, after the removal of a neoplastic mass. IORT has been recently used in early stage cancer as an exclusive radiation modality, rather than as a boost, especially for breast tumours, in particular at the European Institute of Oncology in Milan, where the technique has been called electron intraoperative therapy (ELIOT). Our studies on more than 1000 patients have demonstrated the feasibility of the technique and it is expected that its application will become more widespread in the immediate future. It is important to emphasise that ELIOT relies not only on new technological developments, but also on a multidisciplinary team with clear roles and responsibilities, the establishment of a programme of quality assurance with appropriate guidelines and a comprehensive staff development programme.

1190 ORAL Intraoperative electron beam radiotherapy combined with dose-reduced external beam radiotherapy is highly effective in limb-sparing treatment of extremity soft tissue sarcomas

1190 ORAL Intraoperative electron beam radiotherapy combined with dose-reduced external beam radiotherapy is highly effective in limb-sparing treatment of extremity soft tissue sarcomas

Intraoperative Electron Beam Radiotherapy Combined with Dose-Reduced External Beam Radiotherapy is Highly Effective in Limb-Sparing Treatment of Extremity Soft Tissue Sarcomas

Purpose/Objective: Management of extremity soft tissue sarcomas has changed dramatically during the past 25 years towards a multimodal approach combining limb-sparing surgery with adjuvant radiotherapy. However, severe side effects resulting in clinically significant limb-function impairment are observed in up to 36% of patients after adequately dosed conventional radiotherapy. We review the results of a treatment strategy combining dose-reduced external beam radiotherapy (EBRT) with intraoperative electron beam radiotherapy (IEORT), which has been implemented in Heidelberg 10 years ago, focusing on local control and the incidence of side-effects.

Outcome of phase II study of intraoperative radiation therapy and external-beam radiation therapy plus gemcitabine in patients with locally advanced pancreatic cancer

4197 Background: Chemoradiation therapy including gemcitabine has a significant impact on the survival and quality of life in patients with locally advanced pancreatic cancer. Twice-weekly gemcitabine administration has reported to result in an enhanced radiation sensitizing effect. Our aim was to examine the feasibility and effectiveness of electron-beam intraoperative radiation therapy (IORT) and concurrent external beam radiation therapy (EBRT) with twice-weekly gemcitabine administration as a radiosensitizer. Methods: In twenty patients with registration, five patients with stage III disease (UICC) and 12 patients with stage IV disease have completed the treatment from October 2001 to December 2004. Gemcitabine treatment (600 mg/m2) by 30-minute intravenous infusion was performed 24 hours prior to IORT. IOR was administered at a dose of 24–28 Gy, and directed to the pancreatic tumor and regional lymph nodes. Eight to ten days after IORT, patients were treated with 27 Gy EBRT (1.8 Gy/fraction x 15 frac...

Intraoperative electrons

Intraoperative radiotherapy (IORT) has been used for many years for treating patients with various locally-advanced malignancies, usually combined with external-beam radiation therapy (EBRT). Long-term results confirm that IORT improves local control, which is generally associated with increased survival. Recently, electron-beam IORT has been used as the sole treatment for patients with earlier-stage cancers, especially for breast tumors, with extremely promising results. Most of this work has been done at the European Institute of Oncology in Milan. We report the rationale and techniques of the use of electron intraoperative treatment (ELIOT) and the results of our different clinical studies. In our opinion, ELIOT may be an excellent alternative to EBRT for the treatment of patients with early-stage breast cancer. However, intensive long-term follow-up is needed to fully evaluate local control and possible side effects.

Long-term Results of Intraoperative Electron Beam Irradiation (IOERT) for Patients With Unresectable Pancreatic Cancer

To analyze the effects of a treatment program of intraoperative electron beam radiation therapy (IOERT) and external beam radiation therapy and chemotherapy on the outcome of patients with unresectable or locally advanced pancreatic cancer. From 1978 to 2001, 150 patients with unresectable and nonmetastatic pancreatic cancer received IOERT combined with external beam radiation therapy and 5-fluorouracil-based chemotherapy for definitive treatment. The 1-, 2-, and 3-year actuarial survival rates of all 150 patients were 54%, 15%, and 7%, respectively. Median and mean survival rates were 13 and 17 months, respectively. Long-term survival has been observed in 8 patients. Five patients have survived beyond 5 years and 3 more between 3 and 4 years. There was a statistically significant correlation of survival to the diameter of treatment applicator (a surrogate for tumor size) used during IOERT. For 26 patients treated with a small-diameter applicator (5 cm or 6 cm), the 2- and 3-year actuarial survival rates were 27% and 17%, respectively. In contrast, none of the 11 patients treated with a 9-cm-diameter applicator survived beyond 18 months. Intermediate survival rates were seen for patients treated with a 7- or 8-cm-diameter applicator. Operative mortality was 0.6%, and postoperative and late complications were 20% and 15%, respectively. A treatment strategy employing IOERT has resulted in long-term survival in 8 of 150 patients with unresectable pancreatic cancer. Survival benefit was limited to patients with small tumors. Enrollment of selected patients with small tumors into innovative protocols employing this treatment approach is appropriate.

Preoperative chemoradiation with oral tegafur within a multidisciplinary therapeutic approach in patients with T3-4 rectal cancer

The aim of this study was to evaluate the activity in terms of downstaging histologic patterns of residual tumor and clinical tolerance of a neoadjuvant chemoradiation program with oral tegafur for rectal cancer. From May 1998 to May 2001, 62 consecutive patients with cT(3-4) or cN(+) rectal cancer, or both, were treated with 45-50 Gy (1.8 Gy/day; 25 fractions) and oral tegafur 1200 mg/day. Surgery was performed 6 weeks after the completion of chemoradiation. All patients received a boost with intraoperative electron beam radiotherapy (IOERT) over the presacral space. Grade 3-4 hematologic toxicity consisted on Grade 3 anemia in 1 patient. Nonhematologic toxicity was mild. Fifteen patients (23%) had Grade 3 dermatitis, 16 (25%) had Grade 3, and 2 (3%) had Grade 4 proctitis. The median dose of radiotherapy was 50.4 Gy. Surgery consisted on anterior resection in 38 patients (61%) and abdominoperineal amputation in 24 (39%). Five complete pathologic responses were observed (8%), and 29 patients (47%) had a minimal microscopic residual tumor (mic category). The total downstaging rate was 68%. With a median follow-up of 46 months, the pelvic control rate was 95%, disease-free survival 74.1%, and overall survival 76.5%. Neoadjuvant chemoradiation with oral tegafur is feasible, well tolerated, and active, with the additional advantage of offering the convenience of oral chemotherapy.

Intraoperative single fraction high-dose-rate brachytherapy for head and neck cancers

Purpose To report on the use of single fraction high-dose-rate brachytherapy in delivering localized intraoperative radiation therapy to sites in the head and neck region inaccessible to intraoperative electron beam radiotherapy (IOERT). Methods and materials After maximal surgical resection, 7.5–20 Gy intraoperative high-dose-rate brachytherapy (IOHDR) was delivered to 65 patients using custom-made surface applicators. Results The 1-, 3-, and 5-year local control rates for the entire group were 77%, 69%, and 59%, respectively. The 1-, 3-, and 5-year overall survival rates were 83%, 63%, and 42%, respectively, with a median overall survival of 50 months. There were no major intraoperative or postoperative complications. Conclusions IOHDR can be used to treat selected locally advanced head and neck tumors arising at sites inaccessible to IOERT or at institutions not using IOERT. A prospective multi-institutional study with a larger number of patients treated with IOHDR is needed to firmly establish the efficacy of IOHDR in this population group.

Predictive Factors of Tumor Shrinkage and Histological Regression in Patients who Received Preoperative Radiotherapy for Rectal Cancer

In order to determine the reliable predictors of response to radiotherapy for rectal cancer, we assessed apoptosis, p53 and p21 in biopsy specimens collected before treatment, and investigated the relationships to the histological effect of irradiation and the degree of tumor shrinkage. Ninety-three patients with advanced rectal adenocarcinoma were treated with preoperative irradiation of 20 Gy in 10 fractions in combination with intraoperative electron beam irradiation of 15 Gy. We evaluated tumor grade, pathological tumor regression, biological markers associated with apoptosis and proliferation [apoptotic index (AI), p53, p21 and Ki67], and the degree of tumor shrinkage. Considering positivity of p21 and of apoptosis and negativity of p53 as favorable factors in tumor shrinkage, we compared the degree of shrinkage among the patients using the number of favorable factors as the score. The degree of shrinkage was 41.5 +/- 8.5% in patients with three favorable factors, 31.4 +/- 9.7% in patients with two favorable factors and 26.5 +/- 11.2% in patients with one favorable factor. However, there was no significant difference in the proportion of marked regression according to the number of favorable factors. Histological examination of apoptosis, p21 and p53 in biopsy specimens and scoring were considered to be useful predictive methods for assessing the efficacy of radiotherapy for rectal cancer.

Intraoperative electron beam radiotherapy and human ureteral obstruction

Intraoperative electron beam radiotherapy and human ureteral obstruction

Intraoperative electron beam radiotherapy and human ureteral obstruction

To better quantify the risk of ureteral injury following intraoperative electron beam radiotherapy (IOERT), a review of patients receiving IOERT to the ureter in the course of treatment for locally advanced and/or inoperable pelvic and abdominal malignancies at Mayo Clinic Rochester was performed. Between April 1981 and February 2003, 146 patients with locally advanced malignancies deemed initially unresectable for cure underwent treatment with external beam radiotherapy (EBRT), surgery, and IOERT in which a portion of one or both ureters (164 ureters) were within the IOERT field. Five patients were excluded from analysis because of preexisting hydronephrosis and kidney atrophy. Ninety-two of 141 patients had colorectal/anal malignancies, 26 of 141 had gynecological malignancies, 21 of 141 had retroperitoneal sarcomas, and 2 patients had miscellaneous tumors. IOERT energy ranged from 6 to 20 MeV (median, 12 MeV). IOERT dose ranged from 7.5 to 30.0 Gy (median, 15 Gy). 132 of 141 patients received EBRT either before or after their IOERT procedure at doses of 19.8 to 68.9 Gy (median, 50.0 Gy). 32 (23%) patients had evidence of ureteral obstruction prior to treatment. Follow-up was available in 138 of 141 patients (range: 0.0 to 19.3 years, median 2.1 years). Rates of ureteral obstruction were analyzed for: Type 1.) any cause of obstruction after IOERT; Type 2.) treatment related obstruction secondary to surgery, EBRT, and/or IOERT (excludes patients with documented tumor progression and/or abscess formation obstructing the ureter); Type 3.) delayed obstruction occurring at least one month after surgery and IOERT, (excludes patients with clear tumor progression, abscess formation or patients with stents placed at the time of surgery that were never removed.) See table below. Univariate and multivariate analysis revealed that IOERT dose (P < 0.015) and the presence of ureteral obstruction prior to IOERT (P < 0.001) were associated with an increased risk for ureteral obstruction related to any cause (Type 1.). Prior ureteral obstruction (P < 0.0001) was the only variable associated with an increased risk of ureteral obstruction related to treatment (Type 2.). However, IOERT dose and prior obstruction were not associated with an increased risk of delayed ureteral obstruction (Type 3.) External beam radiotherapy dose, histology, tumor site, size of the IOERT field, and number of IOERT fields had no correlation with an increased risk of ureteral obstruction. The risk of ureteral obstruction following IOERT treatment of the ureter is significant and continues to increase with time, but this risk appears to be less than previously estimated. Patients with previous ureteral involvement are at higher risk for obstruction in the period immediately following resection, IOERT, and EBRT, but they appear to not be at higher risk for late development of ureteral obstruction unrelated to tumor growth or abscess formation. The presence of IOERT dose as a risk factor in this analysis for obstruction related to any cause, including tumor progression, but not to delayed obstruction secondary to chronic radiation effect may reflect that patients with incompletely resected tumors with a higher risk for progression and obstruction of the ureter received higher IOERT doses. In contrast to previous reports from our institution (Shaw, Rad and Onc 18:247–55, 1990), the risk of ureteral obstruction is relatively constant within the range of IOERT doses conventionally employed (10 to 20 Gy).

Application of real-time tumor-tracking and gated radiotherapy system for unresectable pancreatic cancer.

Herein is reported our experience of radiation therapy using a real-time tumor-tracking and gated radiotherapy (RTRT) system for inoperable pancreatic cancer. Three unresectable pancreatic cancer patients were treated with intraoperative electron beam radiation therapy, at the time of open biopsy, and postoperative external beam radiation therapy using an RTRT system with a 2.0 mm diameter gold ball implanted into the pancreas. The total BED'salpha/beta=10 was intended to be equivalent to that of delivering 60 Gy by 2.0 Gy/fraction, while the actual dose schedules were individualized. The movement of the pancreas was analyzed based on the 3-dimensional marker positions during the RTRT. The side effects and tumor responses were evaluated. During the RTRT course, the average movement of markers in the x (left to right), y (cranial to caudal) and z (dorsal to ventral) directions were 3.0 mm (1.7- 5.2 mm), 5.2 mm (3.5 - 6.8 mm) and 3.5 mm (2.7 - 5.1 mm), respectively. During and after the course of postoperative radiation therapy, no acute side effects of RTOG grade II or higher were detected. The objective tumor responses, as evaluated by CT scans 3 months after the treatment, were 2 partial responses and no response in one patient. Using the RTRT technique the margin of treatment planning and the possible errors in target localization were reduced, and the 3-dimensional movement of the internal marker implanted in the pancreas was able to be analyzed.

In vivo dosimetry using radiochromic films during intraoperative electron beam radiation therapy in early-stage breast cancer

Background and purpose: To check the dose delivered to patients during intraoperative electron beam radiation therapy (IOERT) for early breast cancer and also to define appropriate action levels. Patients and methods: Between December 2000 and June 2001, 54 patients affected by early-stage breast cancer underwent exclusive IOERT to the tumour bed using a Novac7 mobile linac, after quadrantectomy. Electron beams (5, 7, 9 MeV) at high dose per pulse values (0.02–0.09 Gy/pulse) were used. The prescribed single dose was 21 Gy at the depth of 90% isodose (14–22 mm). In 35 cases, in vivo dosimetry was performed. The entrance dose was derived from the surface dose measured with thin and calibrated MD-55-2 radiochromic films, wrapped in sterile envelopes. Films were analysed 24–72 h after the irradiation using a charge-coupled-device imaging system. Field disturbance caused by the film envelope was negligible. Results: The mean deviation between measured and expected doses was 1.8%, with one SD equal to 4.7%. Deviations larger than 7% were found in 23% of cases, never consecutively, not correlated with beam energy or field size and with no evidence of linac daily output variation or serious malfunctioning or human mistake. The estimated overall uncertainty of dose measurement was about 4%. In vivo dosimetry appeared both reliable and feasible. Two action levels, for unexplained observed deviations larger than 7 and 10%, were preliminary defined. Conclusions: Satisfactory agreement between measured and expected doses was found. The implementation of in vivo dosimetry in IOERT is suggested, particularly for patients enrolled in a clinical trial.

Surgical management of retroperitoneal sarcomas associated with external and intraoperative electron beam radiotherapy

Aims: To report outcomes of adults with retroperitoneal sarcoma (RS) treated by surgery, external beam radiotherapy (EBRT) and intraoperative electron beam radiotherapy (IORT). Methods: From July 1988 to February 2001; 24 patients with primary and recurrent RS were diagnosed and treated. The median dose and energy of IORT delivered was 15 Gy/9 meV. EBRT dose varies between 45–50 Gy. Results: There were five primary and 19 recurrent tumours. One primary and five recurrent tumours underwent R0 resection. There were 12 liposarcomas and 19 grade I tumours; 13 patients developed local recurrence and three developed distant metastases. Twenty-two patients received IORT associated with EBRT: 11 developed recurrences. Six patients developed Neurotoxicity (4 grade II and 2 grade III). Disease free survival and overall survival at 5 years was 28 and 56% respectively. Conclusions: EBRT with IORT treatment is a promising technique for local control. Lower recurrence rates are associated with radical (R0) surgical procedures.

Long-term results of intraoperative electron beam irradiation for patients with unresectable pancreatic cancer

Long-term results of intraoperative electron beam irradiation for patients with unresectable pancreatic cancer

Phase I Trial of Preoperative Concurrent Doxorubicin and Radiation Therapy, Surgical Resection, and Intraoperative Electron-Beam Radiation Therapy for Patients With Localized Retroperitoneal Sarcoma

The primary objective of this phase I trial was to define the maximum-tolerated dose of external-beam radiation with concurrent fixed-dose continuous-infusion doxorubicin followed by surgical resection and electron-beam intraoperative radiation therapy (EB-IORT) for patients with localized, potentially resectable retroperitoneal sarcomas (RPS). Thirty-five patients with radiographically resectable primary or recurrent intermediate- or high-grade RPS were treated. Doxorubicin was administered each week for 4 or 5 weeks as an initial bolus (4 mg/m2) followed by a 4-day continuous infusion (4 mg/m2/d). Concurrent radiation therapy was administered in escalating doses of 18.0, 30.6, 36.0, 41.4, 46.8, or 50.4 Gy in 1.8-Gy fractions. Radiographic restaging was performed 4 to 8 weeks after chemoradiation, and patients with localized disease underwent surgical resection with EB-IORT (15 Gy). Chemoradiation was completed as outpatient therapy in 31 patients (89%); four patients required hospital admission during chemoradiation or in the postchemoradiation preoperative period. At the highest radiation dose of 50.4 Gy, two (18%) of 11 patients had grade 3 or 4 nausea. Twenty-nine patients (83%) underwent laparotomy; six patients had interval disease progression and did not undergo surgery. Grossly complete resection (R0 or R1) was performed in 26 (90%) of 29 patients who had surgery. EB-IORT was feasible and successfully administered to 22 patients who had R0 or R1 resections. Preoperative chemoradiation, surgical resection, and EB-IORT are feasible for patients with RPS. Preoperative external-beam radiation can be administered to a total dose of 50.4 Gy with continuous-infusion doxorubicin.

Intraoperative radiotherapy electron boost followed by moderate doses of external beam radiotherapy in resected soft-tissue sarcoma of the extremities.

To analyze the patterns of failure and the toxicity profile of intraoperative electron beam radiotherapy (IOERT) after resection of soft tissue sarcomas of the extremities (STS). Forty-five patients with extremity STS were treated with IOERT and moderate-dose postoperative radiotherapy (45-50 Gy). Twenty-six patients were treated for primary disease (PD) and 19 patients for an isolated recurrence (ILR). Tumor size was >5 cm (maximum diameter) in 36 patients (80%), and high-grade histology in PD patients was present in 14 patients (54%). In nine patients, IOERT was used alone, due to previous irradiation or patient refusal. Chemotherapy (neoadjuvant and/or adjuvant) was mainly given to high-grade tumors. Nine patients relapsed in the extremity (20%), and 12 patients in distant sites (28%). Actuarial local control at 5 years was 88% for patients with negative/close margins and 57% for patients presenting positive margins (P=0.04). Five patients (11%) developed neuropathy associated with the treatment. Extremity preservation was achieved in 40 patients (88%). With a median follow-up of 93 months (range: 27-143 months) for the patients at risk, 25 patients remain alive (a 7-year actuarial survival rate of 75% for PD and 47% for ILR; P=0.01). IOERT combined with moderate doses of external beam irradiation yields high local control and extremity preservation rates in resected extremity STS. Peripheral nerves in the IOERT field are dose-limiting structures requiring a dose compromise in the IOERT component to avoid severe neurological damage.

Intraoperative electron beam treatment for pediatric malignancies: The Ohio State University experience.

To report the result of intraoperative electron beam radiation therapy (IOERT) in patients with extensive pediatric tumors. From October 1989 through June 2000, 13 children were treated with chemotherapy, maximal surgery, and 10-15 Gy IOERT at a total of 18 sites. IOERT was used for palliative purposes in 5 children with metastatic disease and in 3 others who were previously treated with external beam radiation (EBRT). The remaining five patients received definitive IOERT. Postoperative EBRT of 35.4-45 Gy was given in 5 patients. After a median follow-up of 42 months (range = 18-63 months), 4 patients were alive and without evidence of disease. Overall and 3 year actuarial survival rates were 31% (4/13) and 26%, respectively. Local control was achieved at 13/18 sites (72%). Poor prognostic factors included metastatic disease, recurrent disease, and the absence of adjuvant EBRT. Two children with Wilms tumors had 100% local control, disease-free survival, and overall survival without the addition of EBRT. A boost dose of IOERT allows for reduction in the dose of EBRT, thereby limiting growth-related morbidity without compromising local control or disease-free survival. Except for Wilms tumors, which achieved 100% local control and disease-free survival, adjuvant EBRT is necessary for successful local control and survival in children with soft tissue sarcomas. Based on this study and others, intraoperative irradiation should be considered for inclusion in prospective, multi-institutional trials designed to treat localized malignancies in young children.