Intraoperative Electron Radiotherapy Research Articles

Neoadjuvant chemoradiation and intraoperative electron irradiation for locally unresectable/borderline resectable pancreas adenocarcinoma.

327 Background: The use of preoperative therapy for pancreatic cancer remains controversial. This study reviews our experience using neoadjuvant chemotherapy and chemoradiation (CRT) followed by surgery with intraoperative electron irradiation (IOERT) for patients with borderline resectable (BR) or unresectable (UR) tumors. Methods: A retrospective review identified 48 patients (pts) with primary BR/UR pancreas adenocarcinoma treated with preop CRT with intent to proceed to curative surgery with IOERT. Seventeen patients did not undergo attempted resection and are excluded (disease progression, 12; medically inoperable, 3; declined surgery, 2). Thirty-one patients proceeded to resection attempt and are the subject of this analysis. Kaplan-Meier survival analysis was performed using log rank test for significance. Median follow up was 19 months (mo). Results: Complete resection (R0) was achieved in 11 pts, R1 in 5, and R2 or not resected (IOERT alone) in 15 patients. Twenty-six pts died (23 of disease, 2 unrelated causes, 1 uncertain). Median overall survival (OS) was 19 mo for all pts. Local progression was detected in only 5 patients (16%) while distant disease developed in 24 (77%). Resection status significantly correlated with OS; R0/R1 patients had a median survival of 23 mo vs. 10 mo for R2/unresected tumors (p = 0.002). Three-year OS was 35% vs. 0%, respectively. Survival was not influenced by tumor location, CA19-9 baseline or response, tumor size, or initial judgment of resectability (BR vs. UR). BR tumors were resectable after neoadjuvant therapy in 9 of 11 patients (R0, 8; R1, 1) while 8 of 20 initially UR tumors underwent resection (R0, 3; R1, 4; R2, 1). Conclusions: Neoadjuvant therapy combined with IOERT has the possibility to improve patient selection for surgical resection and to optimize local therapy. Although the prognosis for locally advanced pancreatic cancer remains poor, survival was superior among patients for whom R0 or R1 resection was achieved. Distant metastasis remained the dominant pattern of failure, and novel systemic agents are needed. Prospective evaluation of the impact of neoadjuvant chemotherapy, CRT, and IOERT is warranted.

Adjuvant chemoradiotherapy with or without intraoperative radiotherapy for the treatment of resectable locally advanced gastric adenocarcinoma

PurposeTo document the long-term efficacy of intraoperative electron radiotherapy (IOERT) followed by concurrent chemotherapy and external-beam radiotherapy (EBRT) in the management of locally advanced gastric cancer. Materials and methodsA total of 97 consecutive patients with T3/4 or N+ gastric adenocarcinoma were enrolled. Fifty-one patients received adjuvant chemoradiotherapy (EBRT group) and 46 received IOERT (dose range, 12–15Gy) followed by chemoradiotherapy (EBRT+IOERT group). ResultsThe 5-year locoregional control rates were 50% and 35% in the two groups with or without IOERT, respectively (p=0.04). Two patients had recurrence within the IOERT field in the EBRT+IOERT group and 14 patients recurred in the same area in the EBRT group (p=0.02). Multivariate analyses revealed that adjuvant IOERT was an independent prognosticator for both local–regional control (p=0.02) and disease-free survival (p=0.05). G3/4 late toxicity was observed in 5 patients in the EBRT+IOERT group, but none in the EBRT group (p=0.02). ConclusionsHigher radiation dose may contribute to the improvement of local control, especially in the field encompassed by IOERT. The addition of IOERT to surgery and adjuvant chemoradiation deserves further investigation in a randomized trial.

Five-year Outcome of a Prospective Study Evaluating Hypofractionated Whole Breast External Beam Irradiation and Tumor Bed Boost with Intra-operative Electron Irradiation (IOERT) For T1/T2 N0 Breast Cancer

Five-year Outcome of a Prospective Study Evaluating Hypofractionated Whole Breast External Beam Irradiation and Tumor Bed Boost with Intra-operative Electron Irradiation (IOERT) For T1/T2 N0 Breast Cancer

Utilization of Interventional Radiology in the Postoperative Management of Patients after Surgery for Locally Advanced and Recurrent Rectal Cancer

The surgical management of locally advanced primary rectal cancer and locally recurrent rectal cancer requires complex operations frequently resulting in complicated postoperative courses. We sought to evaluate the utilization of interventional radiologic (IR) procedures in the management of postoperative complications. Under Institutional Review Board approval, a prospective database of colorectal cancer patients undergoing resection from July 1999 to January 2010 was analyzed. Data collected included demographics, operative procedure, complications, length of stay, and IR utilization. Fisher's exact tests and logistic regression explored associations with necessitating an IR procedure during the postoperative period. Continuous variables were analyzed using Wilcoxon rank sum tests. One hundred and one patients underwent surgery and 66 received intraoperative electron radiotherapy (IOERT). Primary procedures included pelvic exenteration (n = 35), abdominoperineal resection (n = 25), low anterior resection (n = 23), paraaortic node dissection (n = 7), resection of isolated pelvic/retroperitoneal tumor (n = 7), and colectomy (n = 4). Sixty-two patients required multivisceral resection including partial/total cystectomy (n = 30), small bowel resection (n = 25), oophorectomy (n = 15), vaginectomy (n = 12), hysterectomy (n = 12), hepatectomy (n = 3), and nephrectomy (n = 3). Seventeen partial sacral resections and 47 pelvic sidewall resections were also required. One hundred and thirty-eight complications were identified in 72 patients, 30 of which required a procedural intervention. Twenty-seven IR procedures were performed including drainage of fluid collections (n = 14), nephrostomy tube placement (n = 8), arterial embolization (n = 2), inferior vena cava filter placement (n = 2), and pleural drainage (n = 1). Only three reoperations were required, none related to failure of IR procedures. There were no deaths. Estimated blood loss > 2000 mL (P = 0.002), IOERT (P = 0.03), and incomplete resection (P = 0.02) were found to be associated with postoperative IR utilization. Surgery for locally advanced primary rectal cancer and locally recurrent rectal cancer is associated with significant morbidity but low mortality. IR procedures play a significant role in the postoperative management of these patients and may decrease the need for reoperation.

Excellent Local Control and Survival After Intraoperative and External Beam Radiotherapy for Pediatric Solid Tumors

Use of external beam radiotherapy (EBRT) for pediatric solid malignancies is generally limited by the tolerance of normal tissue in developing organs. Intraoperative electron radiotherapy (IOERT) allows a more focal delivery of radiation dose because vital organs can be displaced and avoided during treatment. From February 1983 to July 2003, 20 children underwent IOERT for treatment of locally advanced or recurrent malignancies of the extremity or abdominopelvic area. All patients underwent EBRT and received IOERT doses of 7.5 to 25 Gy with 6-MeV to 15-MeV electrons. At a median follow-up of 11.6 years (range, 2.1 to 25.5 y), 13 patients (65%) were alive and without evidence of disease. Patients who underwent gross total resection had better local control (88% vs. 67%) and survival (71% vs. 33%) than patients for whom the resection was not achieved. Among 7 patients, 11 grade 3 toxicity events were reported. No grade >3 toxicities or second malignancies were observed during follow-up. Use of IOERT in combination with surgery and EBRT in management of pediatric solid malignancies provides excellent local control with reasonable toxicity. IOERT should be considered as an integral part of a multimodality regimen for pediatric solid malignancies, especially for patients with abdominopelvic malignancies.

Long-Term Outcomes After Maximal Surgical Resection and Intraoperative Electron Radiotherapy for Locoregionally Recurrent or Locoregionally Advanced Primary Renal Cell Carcinoma

To report outcomes of a multimodality therapy combining maximal surgical resection and intraoperative electron radiotherapy (IOERT) for patients with locoregionally (LR) recurrent renal cell carcinoma (RCC) after radical nephrectomy or LR advanced primary RCC. From 1989 through 2005, a total of 22 patients with LR recurrent (n = 19) or LR advanced primary (n = 3) RCC were treated with this multimodality approach. The median patient age was 63 years (range 46-78). Twenty-one patients (95%) received perioperative external beam radiotherapy (EBRT) with a median dose of 4,500 cGy (range, 4,140-5,500). Surgical resection was R0 (negative margins) in 5 patients (23%) and R1 (residual microscopic disease) in 17 patients (77%). The median IOERT dose delivered was 1,250 cGy (range, 1,000-2,000). Overall survival (OS) and disease-free survival (DFS) and relapse patterns were estimated using the Kaplan-Meier method. The median follow-up for surviving patients was 9.9 years (range, 3.6-20 years). The OS and DFS at 1, 5, and 10 years were 91%, 40%, and 35% and 64%, 31%, and 31%, respectively. Central recurrence (within the IOERT field), LR relapse (tumor bed or regional lymph nodes), and distant metastases at 5 years were 9%, 27%, and 64%, respectively. Mortality within 30 days of surgery and IOERT was 0%. Five patients (23%) experienced acute or late National Cancer Institute Common Toxicity Criteria (NCI-CTCAE) Version 4 Grade 3 to 5 toxicities. In patients with LR recurrent or LR advanced primary RCC, a multimodality approach of perioperative EBRT, maximal surgical resection, and IOERT yielded encouraging results. This regimen warrants further investigation.

Multimodality therapy including surgical resection (SR) and intraoperative electron radiotherapy (IOERT) for locoregionally recurrent (LRR) or advanced primary malignancies of the urinary bladder (UB) or ureter.

277 Background: For patients (pts) with LRR or advanced primary tumors of the UB or ureter, limited therapeutic options exist. Outcomes of combined SR and IOERT are reported here. Methods: From 1983 to 2009, a total of 17 pts with urothelial (16 pts) or squamous cell carcinoma (1 pt) of the UB (n=13) or ureter (n=4) were treated with SR and IOERT. Pts had LRR after radical cystoprostatectomy or nephroureterectomy (n=15) or advanced primary tumor (n=2). Extent of SR was R0 (microscopic negative margins), R1 (microscopic positive margins), and R2 (gross residual tumor) in 7, 1, and 9 pts, respectively. After maximal SR, IOERT was delivered to the tumor bed. Median IOERT dose and energy delivered were 12.5 Gy (range; 10-20) and 9 MeV (range; 6-18), respectively, with 1 (n=15), 2 (n=1), or 3 (n=1) IOERT fields. Sixteen pts also received perioperative external beam radiotherapy (EBRT) with a median dose of 50.4 Gy (range; 21.6- 60). Five pts received concurrent chemotherapy (CT) with perioperative EBRT. Overall (OS), disease-free survival (DFS) and relapse patterns were estimated from the date of SR and IOERT using the Kaplan-Meier method. Results: The median pt age was 63 years (yrs) (range; 51-76). The median follow-up of surviving pts was 3.6 yrs (range; 1.1-10.0). OS and DFS at 1, 2, and 5 yrs were 53%, 31%, and 16%, and 24%, 18%, and 18%, respectively. Central (within the IOERT field), locoregional (tumor bed or first echelon draining lymphatics), and distant relapse at 2 yrs were 15%, 49%, and 67%, respectively. Seven pts received systemic CT after relapse. Mortality within 30 days of SR and IOERT was 0%. Two pts (12%) experienced grade 4-5 (NCI-CTCAE v. 4) toxicity potentially related to the multimodality therapy. Conclusions: For pts with LRR or advanced primary tumor of the UB or ureter, this multimodality therapy including SR and IOERT resulted in durable OS and DFS in a small but significant number of pts. Both LRR and distant relapse were common, indicating a need for more effective systemic therapy along with more refined locoregional therapy. No significant financial relationships to disclose.

Oncologic outcomes following radical resection with intraoperative electron radiation therapy in patients with recurrent colorectal cancer.

508 Background: Of the 40,000 rectal cancer patients treated annually, up to 15% will experience a local recurrence (LR). Resection only series for LR report 30–60% positive margin rates. For this reason our institution utilizes intra-operative electron radiation therapy (IOERT) in patients undergoing resection of locally advanced rectal cancer recurrences (LA-RRC). The purpose of this study was to evaluate the oncologic outcomes of patients treated for a LA-RRC with resection and IOERT Methods: Under IRB approval a prospective database of patients with LA-RRC undergoing resection and IOERT from April 2001 to January 2010 was analyzed. Demographic, clinical, and pathologic variables were collected. The Kaplan-Meier method estimated 5-year overall survival (OS) and Fisher's Exact test's explored associations for developing a LR. Results: Fifty patients (32 male, mean age 58 ± 11) underwent resection and IOERT (median dose 1500 cGy, energy 9 MeV). Primary procedures included pelvic exenteration (n = 17), APR (n = 10), LAR (n = 7), isolated pelvic/retroperitoneal tumor (n = 7), para-aortic lymphadenectomy (n = 7), and partial colectomy (n = 2). 56% (n = 28) required multi-visceral resections including partial/total cystectomy (n = 14), small bowel resection (n = 10), vaginectomy (n = 6), hysterectomy (n = 3), oophorectomy (n = 3), nephrectomy (n = 2), and other (n = 4). 34 pelvic sidewall resections and 12 partial sacrectomies were required. Margins were R0 in 37 (74%) and R1 in 13 (26%). Median LOS was 10 days and there were no peri-operative deaths. Five-year OS was 32% with a 19-month follow-up of survivors. 32% (n = 16) developed a pelvic LR, of which 2 were isolated and 14 were in the setting of distant metastasis. No difference was noted in OS (p = 0.5) or LR (p = 0.3) in patients with R0 vs. R1 resections. Initial T (p = 0.1), N (p = 0.2), and stage (p = 0.7) were not found to be associated with LR. Conclusions: This study reveals that resection combined with IOERT provides good local control and reasonable long-term survival in patients with LA-RRC. The similar OS and LR following an R0 and R1 resections could be interpreted as a measure of the beneficial effect of IOERT on microscopic disease. No significant financial relationships to disclose.

Abstract P4-10-06: 10-Years Results of Intraoperative Electron Radiotherapy (IOERT) in Boost Modality in Breast Cancer Patients Treated with Breast Conserving Surgery

Abstract Introduction: The aim of this nonrandomized study was to compare the ipsilateral breast tumor recurrence rates in patients with invasive breast cancer, who had been treated with breast conserving surgery and whole breast irradiation and conventional boost or intraoperative electron radiotherapy boost (IOERT). Patients and Methods: 378 patients were included in the study, 188 patients in group 1 (conventional boost) and 190 patients in group 2 (IOERT boost). Patients were comparable with regard to age, menopausal status, tumor size, histological type, grading and axillary lymph node status. Included were patients with invasive breast cancer pT1 and pT2, N0, N1, N2, M0, and breast conserving surgery with clear margins >3mm. Excluded were patients with DCIS only, patients with invasive breast cancers larger than pT2, patients after primary systemic therapy and patients with multicentric disease. All patients (group 1 and group 2) received postoperative whole breast irradiation of 51-56.1 Gy. Group 1 received postoperative electron boost irradiation of 12 Gy after whole breast irradiation and group 2 received one intraoperative electron boost of 9 Gy in a single fraction during surgery before whole breast irradiation. Results: The 10-years actuarial rates of ipsilateral breast tumor recurrence (IBTR), true local recurrence (TLR), distant recurrence (DR) and disease free survival (DFS) were 7.1% (95%CI, 3.2-11.0%), 4.8% (95%CI, 1.5-8.0%), 14,2% (95%CI, 9.1-19.4%) and 82.4% respectively in group1 and 2.7% (95%CI, 0.0-5.9%, P=0.062), 0.7% (95%CI, 0.0-2.0%, P=0.016), 13.6% (95%CI, 5.0-22.2%, P=0.90) and 84.0% (P= 0.76) respectively in group 2. Conclusion: Patients treated with IOERT boost and whole breast irradiation achieve excellent local control rates at 10 years and exhibit statistically significant decreased true local recurrence rates compared to patients treated with whole breast irradiation and conventional electron boost. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-10-06.

Five-year Outcome of a Prospective Study Evaluating Tumor Bed Boost with Intra-operative Electron Irradiation (IOERT) in Breast Conserving Treatment for T1/T2 N0 Breast Cancer

Five-year Outcome of a Prospective Study Evaluating Tumor Bed Boost with Intra-operative Electron Irradiation (IOERT) in Breast Conserving Treatment for T1/T2 N0 Breast Cancer

Long-term Outcomes of the Combined Approach of Maximal Surgical Resection and Intraoperative Electron Radiotherapy for Recurrent or Locally Advanced Renal Malignancies

Long-term Outcomes of the Combined Approach of Maximal Surgical Resection and Intraoperative Electron Radiotherapy for Recurrent or Locally Advanced Renal Malignancies

Safty and acute toxicities of intraoperative electron radiotherapy for patients with abdominal tumors

Objective To investigate the safety and acute toxicities of intraoperative electron radiotherapy for patients with abdominal tumors.Methods From May 2008 to August 2009, 52 patients with abdominal tumors were treated with intraoperative electron radiotherapy,including 14 patients with breast cancer,19 with pancreatic cancer,3 with cervical cancer, 4 with ovarian cancer, 6 with sarcoma, and 6 with other tumors.Fifteen patients were with recurrent tumors.The intraoperative radiotherapy was performed using Mobetron mobile electron accelerator, with total dose of 9 - 18 Gy.In all, 29, 4 and 19 patients received complete resection, palliative resection and surgical exploration, respectively.The complications during the operations and within 6 months after operations were graded according to Common Terminology Criteria for Adverse Events v3.0 (CTC 3.0).Results The median duration of surgery was 190 minutes.Intraoperative complications were observed in 5 patients, including 3 with hemorrhage, 1 with hypotension,and 1 with hypoxemia, all of which were treated conservatively.The median hospitalization time and time to take out stitches was 12 and 13 days, respectively.And the in-hospital mortality was 4% (2/52).Twentyfour patients suffered post-operative adverse events, including 3 postoperative infections.With a median follow-up time of 183 days, 20% of patients sufferred from grade 3 to 5 adverse events, with hematological toxicities being the most common complication, followed by bellyache.Grade 1 and 2 toxicities which were definitely associated with intraoperative radiotherapy was 28% and 4%, respectively.None of grade 3 to 5 complications were proved to be caused by intraoperative radiotherapy.Conclusions Intraoperative electron radiotherapy is well tolerable and could be widely used for patients with abdominal tumors, with a little longer time to take out stitches but without more morbidities and toxicities compared surgery alone. Key words: Abdominal neoplasms/radiotherapy; Radiotherapy, intraoperative electron-ray; Safety; Acute side-response

Long-term outcome of 160 patients with stage IIb cervical carcinoma treated with pre-operative and intra-operative radiotherapy

Objective To investigate the 5-and 10-year survival and complications of patients with stage Ⅱb cervical carcinoma treated by pre-operative photon radiotherapy (POPRT) plus brachytherapy (192Ir) and selective lymphadenectomy hysterectomy (SLH) plus intra-operative electron radiotherapy (IOERT). Methods From February 1997 to May 2007, 160 patients with stage Ⅱb cervical carcinoma were treated by POPRT of 20 Gy in 10 fractions to the whole pelvis, 192Ir brachytherapy of 14 Gy in 2fractions, followed by IOERT of 18 -20 Gy to the whole pelvis during SLH one week after. Results The follow-up rate was 98.1%. The number of patients followed-up for 5 and 10 years was 143 and 135,respectively. The 5-year overall survival rate, disease-free survival rate and local control rate of all patients were 89.4%, 86. 3% and 96. 3%, with the corresponding 10-year rates of 84.4%, 81.0% and 95.0%,respectively. The radiation-induced rectitis and cystitis were 5.0% and 0. 6%, respectivly. The rate of hydronephrosis and lower extremity edema was 6. 3% and 1.3%, respectively. Conclusions Combination of EBRT plus 192Ir brachytherapy and SLH plus IOERT could improve the survival and local control of patiens with cervical carcinoma, with only a few side effects. Key words: Cervical neoplasms/surgery; Cervical neoplasms/radiotherapy; Radiotherapy,intra-operative; Prognosis

SU-GG-T-98: Pencil Beam for Electron Intraoperative Radiotherapy. Early Results from Profile and Percentage Depth Dose Modelling

Purpose: To evaluate the feasibility and the accuracy of pencil beam modelling for electron intraoperative radiotherapy (IORT). Methods and materials: A complete set of dose measurements in water have been performed. They have been made with different source‐to‐applicator‐end distance, bevel angle, applicator size and beam energy. Dose measurements in air have also been made with one applicator size and bevel 0° to obtain initial pencil beam angular spread and fluence intensity profile. An Elekta Precise and a Varian 21 EX linacs have been used. Modelling has been carried out by Tecnicas Radiofisicas (Zaragoza, Spain) adapting a modified Hogstrom's pencil beam implemented in TPS PCRT3D for external Radiotherapy.Results: Different profiles have been obtained according to different machine and applicator design. Lack of accuracy has been kept within 2% or 3% in most of the reference profiles modelled. Nevertheless, it rose to more than 5% for little applicator size, 30° and 45° bevel angle and high energy when modelling Varian beams. Discrepancies for Elekta modelling data have appeared when increasing bevel angle. Additional difficulties have been found when modelling beam edges for little applicators. Besides, percentage depth dose have been modelled for both machines and discrepancies are under investigation. Conclusions: Pencil beam is able to model IORT beams in water for dose delivery calculation. A trade‐off between accuracy and linac time expense should be achieved. Thus, accuracy could be increased if taking extra dedicated data for each combination of energy and applicator size. Then, an improvement of modelling at beam edges should be expected, especially for large bevel angles. The authors expect that further research will lead to calculate absorbed dose in an IORT patient, turning an IORT virtual simulator developed by GMV (Madrid, Spain), Radiance, into a treatment planning system. Supported by grant PSE‐300000‐2009‐5. Ministerio de Ciencia e Innovacion. Spanish Government.

The Italian affair: The employment of parallel‐plate ionization chambers for dose measurements in high dose‐per‐pulse IORT electron beams

At the high dose-per-pulse rates used by some intraoperative radiotherapy (IORT) units, the employment of ionization chambers for dose measurements needs an appropriate correction (k(sat)) for ion recombination. Through a revision of the existing literature, the authors compared different methods for the determination of the recombination correction factor and their impact on clinical dosimetry. A dosimetric characterization of IORT electron beams from a Linac Hitesys Novac7 (Aprilia-Latina, Italy) was performed. Dose-to-water (D(w)) values were measured with dose-per-pulse independent chemical dosimeters (operated by the Italian Primary Standard Dosimetry Laboratory, ENEA) and compared to doses obtained by two different parallel-plate ionization chamber models (Markus and Advanced Markus, PTW, Freiburg, Germany). For dose measurements using ionization chambers, the authors applied two different methods for the determination of the ion recombination correction factor (k(sat)), as suggested in previous articles. The first method is based on the experimental estimation of the free-electron fraction values p; the second one is based on the "nonstandard" two-voltage analysis including the free-electron component. For a Markus type chamber, there is a good agreement between the results on k(sat) and those reported in the literature for both methods, while for the Advanced Markus chamber, no data are available for comparison. Comparing values of D(w) obtained by dose-per-pulse independent dosimeters and by ionization chambers measurements corrected using the two different approaches, the authors can conclude that the k(sat) factor determination is very critical and that only an experimental protocol using ionization chamber intercalibration can be considered reliable.

Mammography findings following electron intraoperative radiotherapy or external radiotherapy for breast cancer treatment

Radiotherapy following breast cancer conserving surgery decreases the risks of local recurrence. Because 85% of breast cancers relapse in or around the surgical bed there has been some debate on the need for irradiating the whole breast. Electron intraoperative radiotherapy (ELIOT) has been used as a viable alternative for conventional external radiotherapy (RT). While the former requires a single dose of 21 Gy in the tumoral bed, the latter requires 5–6 weeks of irradiation with a total dose of 50 Gy and a boost of 10 Gy that irradiates the surgical bed. Herein, we investigated whether any significant differences exist between the mammography findings obtained from patients submitted to one of the two techniques. Two groups of 30 patients each were included in this study. All patients had mammographies taken at 12 and 24 months after finishing treatment. The mammography findings evaluated were: cutaneous thickening (>2 mm), architectural distortion secondary to fibrosis, edema, calcifications (both benign and malignant), and fat necrosis. For all variables studied, there was no statistical difference between the two groups. This indicates that the mammography findings obtained in either 12- or 24-month follow-up periods after breast cancer conserving surgery are similar, regardless of which of the two radiotherapy techniques (ELIOT or RT) is employed as a treatment for breast cancer.

Combined Modality Therapy Including Intraoperative Electron Irradiation for Locally Recurrent Colorectal Cancer

To evaluate survival, relapse patterns, and prognostic factors in patients with colorectal cancer relapse treated with curative-intent therapy, including intraoperative electron radiation therapy (IOERT). From April 1981 through January 2008, 607 patients with recurrent colorectal cancer received IOERT as a component of treatment. IOERT was preceded or followed by external radiation (median dose, 45.5 Gy) in 583 patients (96%). Resection was classified as R0 in 227 (37%), R1 in 224 (37%), and R2 in 156 (26%). The median IOERT dose was 15 Gy (range, 7.5-30 Gy). Median overall survival was 36 months. Five- and 10-year survival rates were 30% and 16%, respectively. Survival estimates at 5 years were 46%, 27%, and 16% for R0, R1, and R2 resection, respectively. Multivariate analysis revealed that R0 resection, no prior chemotherapy, and more recent treatment (in the second half of the series) were associated with improved survival. The 3-year cumulative incidence of central, local, and distant relapse was 12%, 23%, and 49%, respectively. Central and local relapse were more common in previously irradiated patients and in those with subtotal resection. Toxicity Grade 3 or higher partially attributable to IOERT was observed in 66 patients (11%). Neuropathy was observed in 94 patients (15%) and was more common with IOERT doses exceeding 12.5 Gy. Long-term survival and disease control was achievable in patients with locally recurrent colorectal cancer. Continued evaluation of curative-intent, combined-modality therapy that includes IOERT is warranted in this high-risk population.

Proton-Beam, Intensity-Modulated, and/or Intraoperative Electron Radiation Therapy Combined with Aggressive Anterior Surgical Resection for Retroperitoneal Sarcomas

We sought to reduce local recurrence for retroperitoneal sarcomas by using a coordinated strategy of advanced radiation techniques and aggressive en-bloc surgical resection. Proton-beam radiation therapy (PBRT) and/or intensity-modulated radiation therapy (IMRT) were delivered to improve tumor target coverage and spare selected adjacent organs. Surgical resection of tumor and adjacent organs was performed to obtain a disease-free anterior margin. Intraoperative electron radiation therapy (IOERT) was delivered to any close posterior margin. Twenty patients had primary tumors and eight had recurrent tumors. Tumors were large (median size 9.75 cm), primarily liposarcomas and leiomyosarcomas (71%), and were mostly of intermediate or high grade (81%). PBRT and/or IMRT were delivered to all patients, preferably preoperatively (75%), to a median dose of 50 Gy. Surgical resection included up to five adjacent organs, most commonly the colon (n = 7) and kidney (n = 7). Margins were positive for disease, usually posteriorly, in 15 patients (54%). IOERT was delivered to the posterior margin in 12 patients (43%) to a median dose of 11 Gy. Surgical complications occurred in eight patients (28.6%), and radiation-related complications occurred in four patients (14%). After a median follow-up of 33 months, only two patients (10%) with primary disease experienced local recurrence, while three patients (37.5%) with recurrent disease experienced local recurrence. Aggressive resection of retroperitoneal sarcomas can achieve a disease-negative anterior margin. PBRT and/or IMRT with IOERT may possibly deliver sufficient radiation dose to the posterior margin to control microscopic residual disease. This strategy may minimize radiation-related morbidity and reduce local recurrence, especially in patients with primary disease.

Intraoperative Electron Radiotherapy (IOERT) in Patients with Recurrent Rectal Cancer

Intraoperative Electron Radiotherapy (IOERT) in Patients with Recurrent Rectal Cancer

Intraoperative Electron Radiotherapy for the Management of Aggressive Fibromatosis

We analyzed our experience with intraoperative electron radiotherapy (IOERT) followed by moderate doses of external beam radiotherapy (EBRT) after organ-sparing surgery in patients with primary or recurrent aggressive fibromatosis. Indication for IOERT and postoperative EBRT as an individual treatment approach to avoid mutilating surgical procedures was seen when complete surgical removal seemed to be unlikely or impossible. A total of 31 lesions in 30 patients were treated by surgery and IOERT with a median dose of 12 Gy. Median age was 31 years (range, 13-59 years). Resection status was close margin in six lesions, microscopically positive in 13, and macroscopically positive in 12. Median tumor size was 9 cm. In all, 25 patients received additional EBRT, with a median dose of 45 Gy (range, 36-54 Gy). After a median follow-up of 32 months (range, 3-139 months), no disease-related deaths occurred. A total of five local recurrences were seen, resulting in actuarial 3-year local control rates of 82% overall and 91% inside the IOERT areas. Trends to improved local control were seen for older age (>31 years) and negative margins, but none of these factors reached significance. Perioperative complications were found in six patients, in particular as wound healing disturbances in five patients and venous thrombosis in one patient. Late toxicity was seen in five patients. Introduction of IOERT into a multimodal treatment approach in patients with aggressive fibromatosis is feasible with low toxicity and yielded good local control rates even in patients with microscopical or gross residual disease.