High-dose-rate Intraoperative Radiation Therapy Research Articles

Intensification of Local Therapy With High Dose Rate, Intraoperative Radiation Therapy (HDR-IORT) and Extended Resection for Locally Advanced and Recurrent Colorectal Cancer

BackgroundWe report our long-term experience with high dose rate intraoperative radiotherapy (HDR-IORT) in a single, quaternary institution. Patients/MethodsFrom 2004 to 2020, 60 HDR-IORT procedures for locally advanced colorectal cancer (LACC) and 81 for locally recurrent colorectal cancer (LRCC) were done in our institution. Preoperative radiotherapy was done prior to majority of the resections (89%, 125/141). Sixty-nine percent (58/84) of the resections involving pelvic exenterations had >3 en bloc organs resected. HDR-IORT was delivered using a Freiburg applicator. A single 10 Gy fraction was delivered. Margin status was R0 and R1 in 54% (76/141) and 46% (65/141) of the resections, respectively. ResultsWith a median follow-up time of 4 years, 3-, 5-, and 7- year, overall survival (OS) rates were 84%, 58%, and 58% for LACC and 68%, 41%, and 37% for LRCC, respectively. Local progression-free survival (LPFS) rates were 97%, 93%, and 93% for LACC and 80%, 80%, 80% for LRCC, respectively. For the LRCC group, an R1 resection was associated with worse OS, LPFS, and progression-free survival (PFS), preoperative EBRT was associated with improved LPFS and PFS, and ≥2 years disease-free interval was associated with improved PFS. The most common severe adverse events were postoperative abscess (n = 25) and bowel obstruction (n = 11). There were 68 grade 3 to 4 and no grade 5 adverse events. ConclusionsFavorable OS and LPFS can be achieved for LACC and LRCC with intensive local therapy. In patients with risk factors for poorer outcomes, optimization of EBRT and IORT, surgical resection, and systemic therapy are required.

Intensification of local therapy with high-dose rate intraoperative radiation therapy (HDR-IORT) and extended resection for locally advanced and recurrent colorectal cancer.

126 Background: This study reports our long-term experience with high dose rate intraoperative radiotherapy (HDR-IORT) in a single, quaternary institution. Methods: From 2004-2020, 138 consecutive patients with 141 total resections for locally advanced rectal cancer (LARC) (n=60, 43%) defined as T4Nx or T3N+ or locally recurrent rectal cancer (LRRC) (n=81, 57%) were retrospectively reviewed. The median age was 61 years (range 31-83) with 30 patients aged >70 years during surgery. Most patients had preoperative radiotherapy (RT) +/- concurrent chemotherapy (n=125). Thirty-two recurrent cancers received preoperative pelvic reirradiation to a median dose of 36 Gy (range 34.2 – 41.4). HDR-IORT was delivered using isotope iridium-192 in a remote afterloader, and a Freiburg applicator, after macroscopic resection of the tumour. A single 10 Gy fraction was delivered. Fifty-eight of 84 patients who underwent pelvic exenterations had >3 en bloc organs resected, and 96 patients underwent pelvic sidewall dissections. IORT sites included the primary tumour bed (33%), nodal regions (28%) and wider pelvic areas (70%). Resection margin status were R0 in 76 patients (54%) and R1 in 65 (46%). R1 resection was defined as positive (n=53) or close (n=12). R1 resection patients accounted for 61% of pelvic relapses. Results: With a median follow-up time of 4 years, 3-, 5-, and 7- year, overall survival (OS) rates were 75%, 48%, and 45%, respectively (84%,58%, 58% for LARC and 68%,39%, 35% for LRRC). Local progression-free survival (LPFS) of all patients were 88%, 85%, and 85%, respectively (97%, 93%, 93% for LARC and 80%, 80%, 80% for LRRC). On multivariable analysis, an R1 resection was associated with a trend toward poorer OS (p=0.05), while a trend towards worse LPFS (p=0.07) was noted for those without preoperative RT. The most common severe (grade ≥3) adverse events were postoperative abscess (n=25) and bowel obstruction (n=11). Overall, there were 49 (34%) grade 3-4 and no grade 5 adverse events. No intraoperative complications were attributed to IORT. The 30-day mortality rate was 0%. Conclusions: Favorable OS and LPFS can be achieved with intensive local therapy. As R1 resection may be associated with worse survival, optimisation of IORT, surgical resection, and systemic therapy are required. [Table: see text]

Intraoperative radiation therapy for rectal cancer and recurrent intra-abdominal sarcomas

Purpose: The aim of this study was to evaluate the effect of high-dose-rate intraoperative radiation therapy (HDR-IORT) in a multimodality treatment on the local control (LC) and the overall survival (OS) rate in locally advanced rectal cancer (LARC), locally recurrent rectal cancer (LRRC) and recurrent intra-abdominal sarcomas (RS).Materials and methods: A retrospective analysis was performed on 27 patients who were treated with radical resection and HDR-IORT between April 2007 and January 2017. Patient, tumor and surgical characteristics were analyzed and the perioperative (<30 days) and long-term complications (>30 days) were assessed and graded.Results: None of the patients with LARC (n = 4) developed a local recurrence and all patients were still alive at the end of the follow-up. The LC rates of LRRC (n = 17) after one and three years were respectively 48% and 40% and the one, three and five years OS were respectively 93%, 62% and 44%. For RS (n = 6), the LC rates after one and three years were both 33% and the one and three years OS rate were respectively 83% and 46%.Conclusions: The results of our study show that HDR-IORT could be a valuable asset in the multimodality management of LARC, LRRC and RS.

High dose-rate Intra-Operative Radiation Therapy During High Risk Genitourinary Surgery: Initial Observations and a Proposal for its Study in Bladder Cancer.

Background:High dose-rate Intra-Operative Radiation Therapy (HD-IORT) is used to provide effective local control for patients with high-risk locally advanced or recurrent tumors. However, the utility of HD-IORT for patients with bladder cancer has not been studied.Objective:To characterize our institutional experience with HD-IORT in patients with cancer requiring genitourinary surgery, in an effort to identify patients with bladder cancer that may benefit from HD-IORT.Methods:We performed a retrospective review of all patients who have undergone HD-IORT during genitourinary surgery at our institution. Patients were stratified by surgical margin status, and primary outcomes assessed were overall survival, recurrence free survival and 90-day complications. Patients undergoing cystectomy and HD-IORT with sarcomatoid urothelial cancer were compared to a similar cohort undergoing cystectomy alone. A sample case of one such patient is discussed in detail.Results:84 patients at our institution have undergone HD-IORT with genitourinary surgery. Positive surgical margin status was the greatest predictor of both OS (HR = 3.42) and RFS (HR = 2.61). The overall 90-day complication rate was 61%, with wound infections (43%) and GI complications (21%) being most common. 4 of these patients had sarcomatoid urothelial histology, and all are still alive with >2 yrs follow up. This compares to a 52% 1 yr survival in our sarcomatoid urothelial cohort (25 pts) that did not undergo HD-IORT.Conclusions:Our institutional experience with HD-IORT has been promising, particularly among patients with locally advanced disease and sarcomatoid histology. We are currently enrolling patients in a multi-institutional registry to assess the utility of HD-IORT in high risk bladder cancer.

20-Year Experience With Intraoperative High-Dose-Rate Brachytherapy for Pediatric Sarcoma: Outcomes, Toxicity, and Practice Recommendations

To assess outcomes and toxicity of high-dose-rate intraoperative radiation therapy (HDR-IORT) in the management of pediatric sarcoma. Seventy-five pediatric patients underwent HDR-IORT for sarcoma from May 1993 to November 2013. The median age was 9 years old (36 patients were ≤ 6 years old). HDR-IORT was part of initial therapy in 37 patients (49%) and for recurrent disease in 38 patients (51%). Forty-one patients (55%) received HDR-IORT and postoperative external beam RT (PORT), and 22 patients (29%) were previously treated with external beam radiation therapy to the IORT site. Local control (LC), overall survival (OS) and event-free survival (EFS) were estimated using Kaplan-Meier methods. At a median follow-up of 7.8 years for surviving patients, 5-year projected rates of LC, EFS, and OS were 63% (95% confidence interval [CI] 50%-76%), 33% (95% CI 21%-45%), and 43% (95% CI 30%-55%), with a median survival of 3.1 years. The 5-year LC, EFS, and OS rates for patients with recurrent disease were 46% (95% CI, 28%-64%), 30% (95% CI, 13%-46%), and 36% (95% CI, 18%-54%). Acute toxicity ≥ grade 3 occurred in 2 (2.5%) treatments; late toxicity ≥ grade 3 occurred in 4 (5.3%) patients 0.3-9.9 years after HDR-IORT. The incidence of toxicity ≥ grade 3 was not associated with HDR-IORT applicator size, HDR-IORT dose, prior RT or PORT, or prior or postoperative chemotherapy, but all toxicity ≥ grade 3 occurred in patients ≤ 6 years treated with HDR-IORT doses ≥ 12 Gy. HDR-IORT is a well-tolerated component of multimodality therapy for pediatric sarcoma, allowing additional local treatment while reducing external beam exposure. Taking clinical considerations into account, doses between 8-12 Gy are appropriate for HDR-IORT in patients ≤ 6 years of age.

High-dose-rate intraoperative radiation therapy: the nuts and bolts of starting a program

High-dose-rate intraoperative radiation therapy (HDR-IORT) has historically provided effective local control (LC) for patients with unresectable and recurrent tumors. However, IORT is limited to only a few specialized institutions and it can be difficult to initiate an HDR-IORT program. Herein, we provide a brief overview on how to initiate and implement an HDR-IORT program for a selected group of patients with gastrointestinal and pelvic solid tumors using a multidisciplinary approach. Proper administration of HDR-IORT requires institutional support and a joint effort among physics staff, oncologists, surgeons, anesthesiologists, and nurses. In order to determine the true efficacy of IORT for various malignancies, collaboration among institutions with established IORT programs is needed.

High-Dose-Rate Intraoperative Radiation Therapy for Pediatric Sarcoma: Outcomes, Toxicity, and Practice Recommendations

To evaluate outcomes and toxicity of high-dose-rate intraoperative radiation therapy (HDR-IORT) in the management of pediatric sarcoma. Seventy-three consecutive pediatric patients underwent HDR-IORT for sarcoma from May 1993-November 2012. The mean age was 10 years (34 patients ≤6 years). HDR-IORT was a component of the initial therapy in 35 (48.6%) patients and used for recurrent disease in 37 (51.4%). Forty (55.6%) patients received HDR-IORT and postoperative external beam radiation therapy (PORT), and 20 (27.8%) were previously treated with external beam radiation therapy to the IORT site. The median IORT dose was 12 Gy (range, 4-17.5 Gy). When used, the median dose of PORT was 36 Gy (range, 15-53.4 Gy), accounting for HDR-IORT dose to allow for dose reduction. Rates of local control (LC) and overall survival (OS) were estimated using Kaplan-Meier methods; all confidence intervals are 95%. Independent prognostic factors were identified using the Cox stepwise regression analysis. At a median follow-up of 23 months, the 2-year projected rates of LC and OS were 69% (56%-81%) and 60% (47%-72%), with a median survival of 37.4 months. For patients undergoing initial treatment, 2-year projected rates of LC and OS were 95.5% (87%-100%) and 66% (48%-83%); LC and OS for patients with recurrent disease were 50% (32%-67%) and 54% (37%-72%). The addition of PORT was associated with excellent LC for initial therapy (median LC not reached in either case) and improved LC for recurrent disease (median LC 21.9 months vs 16.5 months without PORT), but did not reach significance (p = .132). Improved median OS was also associated with PORT for both initial therapy (median survival 52.9 months vs 7.3 months without PORT) and for recurrent disease (median survival 34 months vs 17.9 months without PORT), p < .001. On multivariate analysis, PORT retained its significance in terms of improved OS (p = .006; HR for death 0.301 (0.13-0.71). Acute ≥ Grade 3 toxicity (< 90 days of HDR-IORT) occurred in 1 (1.3%) patient, consisting of delayed wound healing in an abdominal incision. Late ≥ Grade 3 toxicity (> 90 days of HDR-IORT) occurred in 3 (4.2%) patients, including peripheral neuropathy (1.4%), small bowel infarct (1.4%), and broncho-esophageal fistula (1.4%). The incidence of ≥ Grade 3 toxicity was not associated with HDR-IORT applicator size, HDR-IORT dose, prior RT or PORT, or prior or post-operative chemotherapy, but all ≥ Grade 3 toxicity occurred in patients ≤ 6 years treated with HDR-IORT doses ≥ 12 Gy. HDR-IORT is a well-tolerated component of multimodality therapy for pediatric sarcoma, with the greatest benefits associated with PORT, allowing additional local treatment while reducing external beam exposure. Doses between 8-12 Gy are appropriate for HDR-IORT treatment in pediatric populations’ ≤ 6 years of age.

High-dose-rate Intraoperative Radiation Therapy Combined With Neck Dissection to Salvage Isolated Cervical Nodal Recurrences

Nodal recurrences following treatment for head and neck (H&N) malignancies are difficult to salvage and require complex multidisciplinary expertise. High dose-rate intraoperative radiation therapy (HDR-IORT) allows for immediate targeted treatment while maximally sparing adjacent tissue. Flap reconstruction with unirradiated tissue minimizes complications and provides form and function after maximal resection of disease.

High dose rate intraoperative radiation therapy for recurrent head and neck cancer: The importance of in-field control on survival.

5593 Background: High dose-rate intraoperative radiation therapy (HDR-IORT) offers an opportunity to salvage recurrent patients (pts) and dose-escalate therapy. Methods: From 1/01-2/10, 90 pts with...

Calorimetric approach for 3D dosimetry of high intensity therapeutic electron beams

The technique of High Dose Rate Intra-Operative Radiation Therapy (HDR-IORT) consists in the delivery of irradiation immediately after the removal of a cancerous mass, where the same incision is used to focalize the radiation to the tumour bed. Given its particular characteristics, IORT requires dose measurements that are different from those requested in external radiotherapy treatments. The main reason lies in the fact that in this case a single high dose must be delivered to a target volume whose extension and depth will be determined directly during the operation. Because of this peculiar characteristics, until now there is not a dosimetric system able to detect the electron beam giving at once a realtime response and an extensive spatial measure of the absorbed dose. Within the framework of a research project of the INFN (Italian National Institute of Nuclear Physics), we proposed a new system to overcome the problems, Dosiort. The final set-up is a solid phantom having a density approximately 1 g/cm 3 with sensitive layers of scintillating fibres at fixed positions in a calorimetric configuration for the containment of electrons of energy 4-12 MeV. The prototype will be able to define the physical and geometrical characteristics of the electron beam (energy, isotropy, homogeneity, etc) and to measure the parameters needed to select the energy, the intensity and the Monitor Units (MU) for the exposition: percentage Depth Dose; beam profiles; isodose curves; values of dose per MU. In this work we present the results obtained by using two orthogonal layers of the calorimetric phantom Dosiort, in particular we report the measurement of the dynamic range of the read-out system and the first qualitative study of the results which can be extracted from the measurements taken in a test beam.

High-Dose-Rate Intraoperative Radiation Therapy for Recurrent Head-and-Neck Cancer

To report the use of high-dose-rate intraoperative radiation therapy (HDR-IORT) for recurrent head-and-neck cancer (HNC) at a single institution. Between July 1998 and February 2007, 34 patients with recurrent HNC received 38 HDR-IORT treatments using a Harrison-Anderson-Mick applicator with Iridium-192. A single fraction (median, 15 Gy; range, 10-20 Gy) was delivered intraoperatively after surgical resection to the region considered at risk for close or positive margins. In all patients, the target region was previously treated with external beam radiation therapy (median dose, 63 Gy; range, 24-74 Gy). The 1- and 2-year estimates for in-field local progression-free survival (LPFS), locoregional progression-free survival (LRPFS), distant metastases-free survival (DMFS), and overall survival (OS) were calculated. With a median follow-up for surviving patients of 23 months (range, 6-54 months), 8 patients (24%) are alive and without evidence of disease. The 1- and 2-year LPFS rates are 66% and 56%, respectively, with 13 (34%) in-field recurrences. The 1- and 2-year DMFS rates are 81% and 62%, respectively, with 10 patients (29%) developing distant failure. The 1- and 2-year OS rates are 73% and 55%, respectively, with a median time to OS of 24 months. Severe complications included cellulitis (5 patients), fistula or wound complications (3 patients), osteoradionecrosis (1 patient), and radiation-induced trigeminal neuralgia (1 patient). HDR-IORT has shown encouraging local control outcomes in patients with recurrent HNC with acceptable rates of treatment-related morbidity. Longer follow-up with a larger cohort of patients is needed to fully assess the benefit of this procedure.

Extended pelvic resections for recurrent uterine and cervical cancer: out-of-the-box surgery

Patients with recurrent uterine and cervical cancer have poor prognoses. The objective of this study was to analyze the outcomes of patients with recurrent uterine and cervical cancer who had undergone attempted curative resection of pelvic bone, sidewall muscle, major blood vessels, and/or nerves. We reviewed the records of all 14 patients with recurrent uterine and cervical cancer who had extended pelvic resections at our institution between June 2000 and November 2006. Primary sites of disease were the uterus (11 patients) and cervix (3 patients). Tumor histology was as follows: adenocarcinoma, seven; squamous cell carcinoma, three; leiomyosarcoma, three; and adenosarcoma, one. Previous treatment included hysterectomy, 11; pelvic radiation, 9; chemotherapy, 9; and total pelvic exenteration, 2. Extended pelvic resections included removal of pelvic sidewall muscle, five; bone, five; common and/or external iliac vessel, five; femoral nerve, two; lumbosacral nerve root, one; and obturator nerve, one. Other procedures included total pelvic exenteration, three; posterior exenteration, two; and anterior exenteration, one. Complete resection with negative margins was obtained in 11 (78%) of 14 patients. Seven patients (50%) received high-dose rate intraoperative radiation therapy. Reconstructive procedures included continent or incontinent urinary diversion, four; femoral-femoral arterial bypass, two; myocutaneous flap, two; and urinary ileal interposition, one. Median total operating time was 628 min (range, 345-935 min) and median estimated blood loss was 900 mL (range, 300-16,000 mL). Seven patients (50%) had one or more major complication(s), including pelvic abscess, three; colonic fistula, two; massive intraoperative hemorrhage, one; postoperative bladder perforation, one; thrombosed femoral-femoral graft, one; and disruption of appendicocutaneous urinary anastomosis, one. At a median follow-up of 26 months (range, 5-84 months), ten patients (71%) are alive and four patients (29%) have died of disease at 8, 13, 33, and 42 months postoperatively.

High-Dose-Rate Remote Afterloaders for Intraoperative Radiation Therapy

Intraoperative radiation therapy (IORT) is a treatment option that directly irradiates a surgically exposed tumor or tumor bed while preventing radiation exposure of normal tissues. This article discusses the high-dose-rate intraoperative radiation therapy (HDR-IORT) technique by reviewing the roles of IORT team members, discussing needed equipment and supplies, describing quality assurance processes, explaining the HDR-IORT treatment delivery procedure, and reviewing the post-treatment phase.

High Dose Rate Intraoperative Radiation Therapy for Locally Recurrent Neuroblastoma

High Dose Rate Intraoperative Radiation Therapy for Locally Recurrent Neuroblastoma

TU-D-T-617-06: The Optimization of Dose Delivery for Intraoperative High-Dose-Rate Radiation Therapy Using Curved HAM Applicators

Purpose: To quantify the effect of the curvature of flexible applicators on the dose distribution in high-dose-rate intraoperative radiation therapy (HDR-IORT). Method and Materials: Treatment planning was performed with flat Harrison-Anderson-Mick applicators using as the radioactive source, and dwell times were optimized using dose-point optimization techniques. These optimized dwell times were then used for the curved applicators, and the dose distributions that would actually be delivered to patients were determined. Shallow, moderate, and steep curvatures were considered. The discrepancies in dose distribution resulting from the applicator's curvature were quantified, and the regions receiving significant underdoses or overdoses were identified. Results: The dose directly below the central catheter was strongly dependent on the curvature of the applicator. Steep parabolic curves caused underdoses as large as 19% at the prescribed depth of 1 cm normal to the convex side of the applicator surface. The rate of dose reduction with increasing distance from the applicator surface was also greatly affected by applicator curvature. The local dose distribution was not greatly affected by the number of catheters. On the concave side of the applicator, curvature pushed the isodose curves from the applicator surface, causing overdosing. Data from these experiments could be used to create a simple library of treatment plans for curved geometries to complement existing libraries for flat applicators. Conclusion: The curvature of the applicator profoundly affects dosimetry and can be exploited to optimize coverage of the target during HDR-IORT procedures. To ensure accurate dose delivery, these dose perturbations must be accounted for in the planning process. We recommend maintaining a dosimetry atlas of various applicator sizes and curvatures in addition to one for flat applicators.

A pilot trial of high-dose-rate intraoperative radiation therapy for malignant pleural mesothelioma

Purpose To report results of a phase II trial of high-dose-rate intra-operative radiation therapy (HDR-IORT) for malignant pleural mesothelioma (MPM). Methods and materials Seven patients had extrapleural pneumonectomy with IORT (EPP/IORT) and 6 patients had pleurectomy/decortication with IORT (PD/IORT) between 1994 and 1996. IORT was delivered with 192Ir using a customized applicator with a remote afterloader. A median of 3 sites were treated to a median area of 143 cm 2. A dose of 1500 cGy was prescribed at each site, with 1000 cGy delivered to the mediastinum. Postoperative external beam radiation therapy (EBRT) was given 3–5 weeks later. Median follow-up was 8 months (range, 1–84 months). Results Five patients developed local failure. Two-year local control and survival rates were 35% and 23%, respectively. Mortality was 2/13 (15%), 1 from each surgical group. Serious complications requiring further intervention occurred in 3/6 (50%) of the EPP/IORT group and 1/5 (20%) of the PD/IORT group. Conclusions HDR-IORT after EPP for MPM is prohibitively toxic and has been abandoned, while its use with PD remains in question.

Surgical resection and high dose rate intraoperative radiation therapy for locally recurrent rectal cancer

For intra-pelvic recurrence of rectal cancer, surgical resection is technically difficult and must be aggressive to achieve a high rate of negative resection margins. Resection with clear margins can be curative, particularly for those patients with true anastomotic recurrence. HDR-IORT is a safe, feasible, versatile, logistically sound modality that is highly reliable in delivering radiation to at-risk surgical margins in the pelvis. Despite surgery and IORT, overall local failure rates in this population are 33 to 50 percent. The most important prognostic variable is the state of surgical resection margins. At our institution, in patients with negative and positive resection margins the 2-year actuarial local recurrence rates are 33 percent versus 73 percent and 5-year survival rates are 51 percent versus 16 percent, respectively. On subset analysis, the most favorable outcome was seen in patients with true anastomotic recurrences (78 percent 5-year survival).

Rationale for integrating high-dose rate intraoperative radiation (HDR-IORT) and postoperative external beam radiation with subcutaneous amifostine for the management of stage III/IV head and neck cancer

Locoregional recurrence remains a major obstacle to achieving cure of locally advanced head and neck cancers despite maximal resection and postoperative external beam radiation therapy (EBRT). Locoregional failure occurs in 30% to 40% of high-risk resected head and neck cancer patients after standard postoperative EBRT. In an effort to overcome this problem, a number of strategies have been designed to enhance the effectiveness of radiation including concurrent postoperative chemoradiation, accelerated radiation schedules, incorporation of targeted biologic therapies, and improved radiation delivery techniques such as intensity modulated radiation and high-dose rate (HDR) intraoperative radiation therapy. Intraoperative radiation therapy (IORT) represents an important approach to improve outcome in head and neck cancer patients treated with definitive surgery. High-dose rate IORT is defined as the delivery of a single, large dose of radiation at the time of surgery when the tumor bed is exposed. In conjunction with EBRT, HDR-IORT offers several advantages including: (1) conformal delivery of a large dose of radiation while the tumor bed is precisely defined, minimizing the risk of a geographic miss; (2) potential for subsequent dose reduction of EBRT; (3) shortening overall treatment time; and (4) dose-escalation. Because mucositis represents the dose-limiting acute toxicity and xerostomia ranks as the most common long-term quality-of-life complaint, a reduction of the EBRT dose may provide an important benefit in reducing toxicity, especially when combined with the radioprotectant amifostine (Ethyol, WR-2721; MedImmune, Inc, Gaithersburg, MD). The purpose of this article is to review the rationale for integrating HDR-IORT with a reduced dose of postoperative EBRT combined with amifostine to improve locoregional control and quality of life outcomes in advanced-stage resected head and neck cancer patients.

Recurrent cervical cancer.

There are limited treatment options for patients with recurrent cervical carcinoma. Because of low response rates and a negligible impact on long-term survival, the use of chemotherapy in patients with unresectable recurrent disease should be considered palliative. Generally, radiation therapy in previously irradiated patients is considered palliative. For patients who develop recurrent disease after definitive surgery who have not received prior radiation therapy, salvage radiation therapy is the treatment of choice. Similarly, patients who have received definitive primary radiation therapy are candidates for surgical resection of their recurrence. However, there are specific criteria for surgical resection. Radical hysterectomy may be an option for the very rare patient with a small (<2 cm) centrally located recurrence in the cervix or vaginal fornices. However, for most patients, pelvic exenteration remains the only therapeutic option that offers the possibility of long-term survival. Patients who are candidates for exenteration are those with central local recurrences that have not extended to the pelvic sidewalls. The introduction of high-dose-rate intraoperative radiation therapy (HDR-IORT) combined with radical surgical resection has widened the scope of patients who may be offered surgery. Patients who in the past may not have been surgical candidates may benefit from radical surgical resection combined with HDR-IORT. All patients who are surgically fit and have undergone previous radiation therapy should be considered for surgical resection for centrally located recurrences. Patients whose recurrences extend close to the pelvic sidewalls should be referred to centers where HDR-IORT is available.

High-dose-rate intraoperative radiation therapy (HDR-IORT) for retroperitoneal sarcomas

Purpose: Retroperitoneal sarcomas represent a formidable challenge to the treating oncologist due to their location, large size, and poor prognosis. The purpose of this study was to determine if the addition of high-dose-rate intraoperative radiation therapy (HDR-IORT) to surgery and external beam radiotherapy (EBRT) would improve the outcome in these patients. Methods and Materials: Thirty-two patients with retroperitoneal soft tissue sarcoma were prospectively treated according to a protocol that included maximal tumor resection, HDR-IORT, and postoperative EBRT when feasible. Twelve patients presented with primary and 20 with locally recurrent disease. The tumors were high-grade in 20 patients and low-grade in 12 patients. Complete gross resection was achieved in 30 patients. HDR-IORT was given to a dose of 12–15 Gy. Additional EBRT was given to 78% of patients to a dose of 45–50.4 Gy. The two patients with gross residual disease received an additional I-125 permanent implant to a median peripheral dose of 140–160 Gy. The median follow-up was 33 months (range 1–77 mo). Results: The 5-year actuarial local control rate for the whole group was 62%. For patients with primary disease, the local control rate was 74% compared to 54% in patients with recurrent disease ( p = 0.4). The overall 5-year distant metastasis-free survival rate was 82%. In patients with high-grade tumors the rate was 70% vs. 100% in those with low-grade tumors. This difference was statistically significant, p = 0.05. The 5-year disease-free and overall survival rates were 55% and 45%, respectively. The most common type of post-treatment complication was gastrointestinal obstruction (18%) followed by fistula formation (9%), peripheral neuropathy (6%), hydronephrosis (3%), and wound complication (3%). Conclusions: We are encouraged by the favorable local control rate and the acceptable morbidity with this new technique applied to a challenging patient population.