Intraoperative high-dose-rate brachytherapy: An American Brachytherapy Society consensus report.

PURPOSE: This report presents recommendations from the American Brachytherapy Society for the use of intraoperative high-dose-rate (IOHDR) brachytherapy. METHODS AND MATERIALS: Members of the American Brachytherapy Society with expertise in IOHDR formulated this document based on their clinical experience and a review of the literature. This report covers the use of IOHDR in colorectal cancer, soft tissue sarcoma, gynecologic cancers, head and neck cancers, and pediatric cancers. This report does not cover intraoperative brachytherapy for breast cancer. Details about treatment planning and delivery are emphasized so this document can serve as a guide to practices implementing this technique. RESULTS: IOHDR brachytherapy is generally most beneficial for patients with either close or positive margins and/or recurrent disease in a previous resection bed or previously irradiated area. IOHDR brachytherapy requires a well-coordinated multidisciplinary team. IOHDR brachytherapy is recommended in the treatment of both recurrent and primary locally advanced disease for colorectal and gynecologic malignancies, soft tissue sarcoma, and selected head and neck and pediatric malignancies. Other techniques such as perioperative fractionated brachytherapy are also acceptable in many cases with some advantages and disadvantages compared to IOHDR. CONCLUSIONS: IOHDR brachytherapy is a specialized technique in radiation therapy with unique properties and advantages in cancer control. Special considerations for treatment planning and delivery are outlined herein.

Positive peritoneal cytology is highly predictive of prognosis and relapse patterns in stage III (FIGO 2009) endometrial cancer.

OBJECTIVES: According to the updated FIGO system, positive peritoneal cytology does not affect endometrial cancer stage. This revision may reduce rates of obtaining cytology, with unclear implications in advanced disease. This study evaluates the significance of positive cytology in stage III (FIGO 2009) endometrial cancer. METHODS: Eligible patients received treatment for stage III endometrial cancer at a single institution and had peritoneal cytology performed. RESULTS: Of 196 patients, 58% were ≥ 60 years old, 48% had deep myometrial invasion, 71% lymphovascular invasion, 25% cervical invasion, 37% adnexal involvement, 79% nodal involvement, and 46% aggressive histology. Positive cytology was present in 23% (45/196) and significantly associated with cervical stromal invasion, adnexal involvement, and aggressive histology (P ≤ 0.03). There was no significant difference in rates of lymphadenectomy, chemotherapy, or radiation between negative and positive cytology groups. At a median follow-up of 47 months, the 5-year freedom from relapse was 39% for positive cytology vs. 69% for negative, disease-specific survival 42% vs. 77%, and overall survival 34% vs. 72% (P < 0.001). Positive cytology correlated with higher recurrence rates in the para-aortic nodes and peritoneum (30% vs. 9%, 23% vs. 4%; P ≤ 0.008). When controlling for adverse features including aggressive histology, positive cytology was associated with an increased hazard for relapse (HR 2.3; P = 0.002) and death (HR 2.9; P < 0.001). CONCLUSIONS: In stage III endometrial cancer, positive cytology independently predicts outcome and is associated with distinct relapse patterns. Obtaining peritoneal cytology in stage III endometrial cancer is critical.

Impact of incorporating an algorithm that utilizes sentinel lymph node mapping during minimally invasive procedures on the detection of stage IIIC endometrial cancer.

OBJECTIVE: To determine whether the frequency of cases diagnosed with stage IIIC endometrial cancer is affected by the incorporation of a modified surgical lymph node assessment. METHODS: Since 2008, we have increasingly utilized a modified nodal assessment using an algorithm that incorporates SLN mapping. For this analysis, we identified all cases of newly diagnosed endometrial cancers undergoing a minimally invasive staging procedure not requiring conversion to laparotomy from 1/1/08 to 12/31/10. Procedures were categorized as standard, modified, and hysterectomy only. Differences were based on time period: 2008 (Y1), 2009 (Y2), and 2010 (Y3). Appropriate statistical tests were used. RESULTS: We identified a total of 507 cases. The distribution of cases was 143 (Y1), 190 (Y2), and 174 (Y3). Tumor grade (P=0.05) and high-risk histologies (P=0.8) did not differ during the 3 time periods. A standard staging procedure was performed in the following cases: Y1 (93/143; 65%), Y2 (66/166; 35%), and Y3 (40/164; 23%) (P<0.001). Median operative times were as follows: Y1 (218 min), Y2 (198 min), and Y3 (176.5 min) (P<0.001). The median numbers of total lymph nodes removed among cases with at least 1 node retrieved were: Y1 (20); Y2 (10); Y3 (7) (P<0.001). Cases diagnosed as stage IIIC were as follows: Y1 (10/143; 7%), Y2 (15/166; 7.9%), and Y3 (13/164; 7.5%) (P=1.0). CONCLUSIONS: The incorporation of a modified staging approach utilizing the SLN mapping algorithm reduces the need for standard lymphadenectomy and does not appear to adversely affect the rate of stage IIIC detection.

Extended pelvic resections for recurrent or persistent uterine and cervical malignancies: an update on out of the box surgery.

OBJECTIVE: To update our report on the outcome of patients who underwent extended pelvic resection (EPR) for recurrent or persistent uterine and cervical malignancies. METHODS: We reviewed the records of all patients who underwent EPR between 6/2000 and 07/2011. EPR was defined as an en-bloc resection of a pelvic tumor with sidewall muscle, bone, major nerve, and/or major vascular structure. Complications up to 180 days post surgery were analyzed. Survivals were estimated using the Kaplan-Meier method. RESULTS: We identified 22 patients. Median age at the time of EPR was 58 years (range, 36-74). Median tumor diameter was 5.4 cm (range, 1.5-11.2). Primary tumor sites included: uterus, 13; cervix, 7; synchronous uterus/cervix, 1; and synchronous uterus/ovary, 1. The EPR structures were: muscle, 13; nerve, 10; bone, 8; vessel, 5. Complete gross resection with microscopically negative margins (R0 resection) was achieved in 17 patients (77%). There were no perioperative mortalities. Major postoperative complications occurred in 14 patients (64%). The two most common morbidities were pelvic abscesses and peripheral neuropathies. Median follow-up time was 28 months (range, 6-99). The 5-year overall survival (OS) for the entire cohort was 34% (95% CI, 13-57). For the 17 patients who had an R0 resection, the 5-year OS was 48% (95% CI, 19-73). In patients with positive pathologic margins (n=5), the 5-year OS was 0%. CONCLUSION: EPR was associated with prolonged survival when an R0 resection was achieved. The high rate of postoperative complications remains a hallmark of these procedures and properly selected patients should be extensively counseled preoperatively.

Sentinel lymph node mapping for endometrial cancer improves the detection of metastatic disease to regional lymph nodes.

OBJECTIVE: To compare the incidence of metastatic cancer cells in sentinel lymph nodes (SLN) vs. non-sentinel nodes in patients who had lymphatic mapping for endometrial cancer and to determine the contribution of metastases detected on ultrastaging to the overall nodal metastasis rate. METHODS: All patients who underwent lymphatic mapping for endometrial cancer were reviewed. Cervical injection of blue dye was used in all cases. Sentinel nodes were examined by routine hematoxylin and eosin (H&E), and if negative, by standardized institutional pathology protocol that included additional sections and immunohistochemistry (IHC). RESULTS: Between 09/2005 and 03/2010, 266 patients with endometrial cancer underwent lymphatic mapping. Sentinel node identification was successful in 223 (84%) cases. Positive nodes were diagnosed in 32/266 (12%) patients. Of those, 8/266 patients (3%) had the metastasis detected only by additional section or IHC as part of SLN ultrastaging. Excluding the 8 cases with positive SLN on ultrastaging only, 24/801 (2.99%) SLN and 30/2698 (1.11%) non-SLN were positive for metastatic disease (p=0.0003). CONCLUSION: Using a cervical injection for mapping, metastatic cells from endometrial cancer are three times as likely to be detected in SLN than in the non-sentinel nodes. This finding strongly supports the concept of lymphatic mapping in endometrial cancer to fine tune the nodal dissection topography. By adding SLN mapping to our current surgical staging procedures we may increase the likelihood of detecting metastatic cancer cells in regional lymph nodes. An additional benefit of incorporating pathologic ultrastaging of SLN is the detection of micrometastasis, which may be the only evidence of extrauterine spread.

A nomogram for predicting overall survival of women with endometrial cancer following primary therapy: toward improving individualized cancer care.

OBJECTIVES: Traditionally we have relied mainly on final FIGO stage to estimate overall oncologic outcome in endometrial cancer patients. However, it is well known that other patient factors may play equally important roles in outcome. Our objective was to develop a clinically useful nomogram in the hope of providing a more individualized and accurate estimation of overall survival (OS) following primary therapy. METHODS: Using a prospectively maintained endometrial cancer database, 1735 patients treated between 1993 and 2008 were analyzed. Characteristics known to predict OS were collected. For each patient, points were assigned to each of these 5 variables. A total score was calculated. The association between each predictor and the outcome was assessed by multivariable modeling. The corresponding 3-year OS probabilities were then determined from the nomogram. RESULTS: The median age was 62 years (range, 25-96). Final grade included: G1 (471), G2 (622), G3 (634), and missing (8). Stage included: IA (501), IB (590), IC (141), IIA (36), IIB (75), IIIA (116), IIIB (6), IIIC (135), IVA (7), and IVB (128). Histology included: adenocarcinoma (1376), carcinosarcoma (100), clear cell (62), and serous (197). Median follow-up for survivors was 29.2 months (0-162.2 months). Concordance probability estimator for the nomogram is 0.746+/-0.011. CONCLUSION: We developed a nomogram based on 5 easily available clinical characteristics to predict OS with a high concordance probability. This nomogram incorporates other individualized patient variables beyond FIGO stage to more accurately predict outcome. This new tool may be useful to clinicians in assessing patient risk when deciding on follow-up strategies.

Small cell neuroendocrine carcinoma of the cervix: Analysis of outcome, recurrence pattern and the impact of platinum-based combination chemotherapy.

OBJECTIVES: To analyze progression-free (PFS) and overall survival (OS) in patients with small cell neuroendocrine carcinoma of the cervix (SCNEC), and to determine whether platinum-based combination chemotherapy is beneficial for this population. METHODS: We performed a retrospective analysis of all patients with SCNEC who were treated at our institution between 1/1990 and 2/2007. Patients were excluded if pathologic diagnosis was not confirmed at our institution. Standard statistical methods were utilized. RESULTS: Seventeen patients met inclusion criteria. The estimated 3-year PFS and OS rates for the entire group were 22% and 30%, respectively. Median time to progression was 9.1 months. Extent of disease was the only significant prognostic factor. Median OS for patients with early stage disease (IA1-IB2) was 31.2 months and 6.4 months for patients with advanced stage disease (IIB-IV, P=0.034). In the early-stage disease group, the 3-year distant recurrence-free survival rate was 83% for patients who received chemotherapy and 0% for patients who did not receive chemotherapy as part of their initial treatment (P=0.025). The estimated 3-year OS rate was 83% for patients who received and 20% for patients who did not receive chemotherapy as part of their initial treatment (P=0.36). CONCLUSION: Given the rarity of SCNEC this retrospective analysis is limited by a small number of patients. However, the natural history of this rare disease is akin to small cell lung cancer and the prognosis is poor due to the tumor's propensity for distant spread. The treatment should conform to the treatment of small cell lung cancer.

The incidence of pelvic lymph node metastasis by FIGO staging for patients with adequately surgically staged endometrial adenocarcinoma of endometrioid histology.

The seminal Gynecologic Oncology Group study on surgical pathologic spread patterns of endometrial cancer demonstrated the risk of pelvic lymph node metastasis for clinical stage I endometrial cancer based on tumor grade and thirds of myometrial invasion. However, the FIGO staging system assigns surgical stage by categorizing depth of myometrial invasion in halves. The objective of this study was to determine the incidence of pelvic lymph node metastasis in endometrial cancer based on tumor grade and myometrial invasion as per the current FIGO staging system. We reviewed the records of all patients who underwent primary surgical staging for clinical stage I endometrial cancer at our institution between May 1993 and November 2005. To make the study cohort as homogeneous as possible, we included only cases of endometrioid histology. We also included only patients who had adequate staging, which was defined as a total hysterectomy with removal of at least eight pelvic lymph nodes. During the study period, 1036 patients underwent primary surgery for endometrial cancer. The study cohort was composed of the 349 patients who met study inclusion criteria. Distribution of tumor grade was as follows: grade 1, 80 (23%); grade 2, 182 (52%); and grade 3, 87 (25%). Overall, 30 patients (9%) had pelvic lymph node metastasis. The incidence of pelvic lymph node metastasis in relation to tumor grade and depth of myometrial invasion (none, inner half, and outer half) was as follows: grade 1-0%, 0%, and 0%, respectively; grade 2-4%, 10%, and 17%, respectively; and grade 3-0%, 7%, and 28%, respectively. We determined the incidence of pelvic nodal metastasis in a large cohort of endometrial cancer patients of uniform histologic subtype in relation to tumor grade and a one-half myometrial invasion cutoff. These data are more applicable to current surgical practice than the previously described one-third myometrial invasion cutoff results.

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.

Management of uterine malignancy found incidentally after supracervical hysterectomy or uterine morcellation for presumed benign disease.

Patients who have undergone supracervical hysterectomy or uterine morcellation for presumed benign uterine disease and are found to have malignancy on final pathology represent a management dilemma. Our goal was to analyze our experience and make observations regarding staging, treatment, and outcomes. We performed a retrospective case series of patients referred to our institution with uterine malignancy who previously underwent supracervical hysterectomy or uterine morcellation at the time of original surgery for presumed benign uterine disease. Between January 2000 and March 2006, 17 patients with uterine malignancy were identified. Following initial surgery, 15 (88%) patients had presumed stage I disease and 2 (12%) patients had stage III disease. Two (15%) of 13 patients who underwent completion surgery were upstaged; both had leiomyosarcoma (LMS) originally resected with morcellation. Ten of 11 patients whose stage was confirmed with secondary surgery remain disease free. None of the patients who initially underwent supracervical hysterectomy without morcellation were upstaged by secondary surgery. The median follow-up interval was 30 months (range, 2-90 months). Reoperation for completion surgery and staging is important when uterine malignancy is found incidentally after morcellation or supracervical hysterectomy for presumed benign uterine disease. Approximately 15% of patients will be upstaged by reexploration, particularly those with LMS who underwent morcellation. Patients who undergo completion surgery with restaging and are not upstaged appear to have a good prognosis. Surgical staging is valuable for prognosis and may alter postoperative treatments.

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).

Radical surgical resection and high-dose intraoperative radiation therapy (HDR-IORT) in patients with recurrent gynecologic cancers.

OBJECTIVE: To determine the outcome for patients with recurrent gynecologic tumors treated with radical resection and combined high-dose intraoperative radiation therapy (HDR-IORT). METHODS AND MATERIALS: Between November 1993 and June 1998, 17 patients with recurrent gynecologic malignancies underwent radical surgical resection and high-dose-rate brachytherapy. The mean age of the study group was 49 years (range 28-72 years). The site of the primary tumor was the cervix in 9 (53%) patients, the uterus in 7 (41%) patients, and the vagina in 1 (6%) patient. The treatment for the primary disease was surgery with or without adjuvant radiation in 14 (82%) patients and definitive radiation in 3 (18%) patients. The current surgery consisted of exenterative surgery in 10 (59%) patients and tumor resection in 7 (41%) patients. Complete gross resection was achieved in 13 (76%) patients. The mean HDR-IORT dose was 14 Gy (range 12-15). Additional radiation in the form of permanent Iodine-125 implant was given to 3 of 4 patients with gross residual disease. The median peripheral dose was 140 Gy. RESULTS: With a median follow-up of 20 months (range 3-65 months), the 3-year actuarial local control (LC) rate was 67%. In patients with complete gross resection, the 3-year LC rate was 83%, compared to 25% in patients with gross residual disease, p < 0.01. The 3-year distant metastasis disease-free and overall survival rates were 54% and 54%, respectively. The complications were as follows: gastrointestinal obstruction, 4 (24%); wound complications, 4 (24%); abscesses, 3 (18%); peripheral neuropathy, 3 (18%); rectovaginal fistula, 2 (12%); and ureteral obstruction, 2 (12%). CONCLUSION: Radical surgical resection and combined IORT for patients with recurrent gynecologic tumors seems to provide a reasonable local-control rate in patients who have failed prior surgery and/or definitive radiation. Patient selection is very important, however, as only those patients with complete gross resection at completion of surgery appear to benefit most from this radical approach in the salvage setting.

Adjuvant radiotherapy for margin-positive high-grade soft tissue sarcoma of the extremity.

PURPOSE: Adjuvant radiotherapy (RT) has been shown to improve local control in patients with soft tissue sarcoma of the extremities (STS). The specific impact of adjuvant radiation on patients with positive margins, however, has not been clearly defined. The purpose of this study was to determine if adjuvant RT improves local control in patients with high-grade STS who had positive margins of resection. METHODS AND MATERIALS: Between 8/82 and 2/97, 110 adult patients with primary high-grade STS of an extremity underwent limb sparing surgery and were found to have a histologically positive microscopic surgical margin. Ninety-one (83%) received RT and 19 (17%) had no RT. The two groups were balanced with regard to size, site, location, and tumor depth. Adjuvant RT was delivered with brachytherapy (BRT) alone in 34 patients, external beam radiotherapy (EBRT) alone in 33 patients, or BRT+EBRT in 24 patients. The BRT dose was 45 Gy when used alone and 15-20 Gy when used as a boost. The EBRT dose was 60-70 Gy when used alone and 45-50 Gy when given with BRT. The median follow-up time was 41 months (range, 3-186 months). RESULTS: The overall 5 year local control rate was 71%. This rate was significantly higher in the RT group compared to the no RT group (74% vs. 56%, respectively) (p = 0.01). On univariate analysis, lower extremity site and proximal location were also found to be predictors of improved local control (p = 0.03 and 0.03, respectively). However, only proximal location and the use of RT retained their significance as predictors of improved local control on multivariate analysis (p = 0.003 and 0.01, respectively). The overall 5-year distant relapse-free survival, disease-free survival, and overall survival rates were 54%, 44%, and 53%, respectively. No statistical differences were found in these survival rates between RT and no RT groups. CONCLUSION: Based on this study, adjuvant radiotherapy seems to improve local control in patients with high-grade STS of the extremity with positive margins. However, local recurrence still occurs in a substantial proportion of patients, mandating further need for improvement.

Continent urinary diversion and low-rectal anastomosis in patients undergoing exenterative procedures for recurrent gynecologic malignancies.

OBJECTIVE: The aim of this study was to review the complications associated with continent urinary diversion and associated procedures in patients with gynecologic malignancies. METHODS: We retrospectively reviewed the medical records of all patients who underwent construction of a continent urinary conduit between October 1991 and October 1998 on the Gynecology Service at Memorial Sloan-Kettering Cancer Center. RESULTS: Thirty-three patients were identified, of whom 22 underwent total pelvic exenteration, 8 underwent anterior exenteration, and 3 underwent urinary diversion procedures only. Complications associated with the urinary diversion procedure included ureteral strictures (2), pouch leakage (2), mild hydronephrosis, (6), pyelopnephritis (2), nocturnal incontinence (5), and difficulty with self-catheterization (2). Additional procedures performed concomitantly with continent urinary diversion and exenteration included pelvic reconstruction (18), low-rectal anastomosis (13), and intraoperative radiation therapy (9). The most significant morbidity was seen in patients undergoing concomitant low-rectal anastomosis, in whom the rate of anastomotic leaks was 54% (7 of 13 patients). CONCLUSIONS: Continent urinary diversion can successfully be accomplished at the time of exenteration in patients with recurrent gynecologic malignancies. The rate of major complications related to the urinary diversion is small and most complications can be managed nonsurgically. The greater than 50% rate of anastomotic leaks in patients undergoing concomitant low-rectal anastamosis suggests that such anastomosis should not be undertaken in this group of patients.

High-dose-rate intraoperative brachytherapy for recurrent colorectal cancer.

PURPOSE: Management of locally recurrent colorectal adenocarcinoma represents a significant challenge. Many of these tumors adhere to or invade into vital pelvic structures rendering surgery or external beam radiotherapy (EBRT) as palliative treatment. Therefore, a treatment approach was developed to evaluate the role of high-dose-rate intraoperative brachytherapy (HDR-IORT) and surgery as a component of therapy in the management of locally recurrent colorectal cancer. This is an update of our preliminary report with longer follow-up and larger patient numbers. METHODS AND MATERIALS: Between January 1992 and September 1998, 74 patients with locally recurrent rectal cancer were treated with surgery and HDR-IORT. Additional EBRT was given to 29 patients, and 33 patients received 5-fluorouracil based chemotherapy. All patients underwent complete gross resection, and 21 of 74 had positive microscopic margin. The dose of HDR-IORT ranged from 10 to 18 Gy. RESULTS: With a median follow-up of 22 months, the 5-year local control, distant metastasis disease-free, disease-free, and overall survival rates were 39%, 39%, 23%, and 23%, respectively. The only predictor of improved local control was a negative margin of resection with a 5-year local control rate of 43%, compared to 26% in those with positive margin (p = 0.02). For overall survival, a negative microscopic margin (p = 0.04) and the use of IORT + EBRT (p = 0.04) were significant predictors of improved survival. The incidence of peripheral neuropathy was 16%. CONCLUSION: The results with HDR-IORT in this group of patients are encouraging. Further improvements in local and distant control are still needed.

Morbidity of adjuvant brachytherapy in soft tissue sarcoma of the extremity and superficial trunk.

PURPOSE: We have previously shown that adjuvant brachytherapy (BRT) improves local control in soft tissue sarcoma (STS) of the extremity and superficial trunk. A detailed assessment of the morbidity of this approach has not been examined. The purpose of this study was to evaluate the toxicity associated with adjuvant BRT in terms of wound complications, bone fracture, and peripheral nerve damage. METHODS AND MATERIALS: Between July 1982 and June 1992, 164 adult patients with STS of the extremity or superficial trunk were randomized intraoperatively to receive or not to receive BRT after complete resection. BRT was delivered with (192)Ir to a total dose of 42-45 Gy. The BRT and no-BRT arms were balanced with regard to age, sex, presentation (primary vs. recurrent), site, grade, size, and depth. Morbidity was assessed in terms of significant wound complication, bone fracture, and peripheral nerve damage (grade > or = 3). The significant wound complications were defined as those wound problems requiring operative revision for coverage or threatened limb loss, persistent seroma requiring repeated aspirations and/or drainage, wound separation > 2 cm, hematoma > 25 ml, and/or purulent wound discharge. The median follow-up was 100 months. RESULTS: The significant wound complication rate was 24% in the BRT group and 14% in the no-BRT group, (p = 0.13). The rate of wound reoperation, however, was significantly higher in the BRT arm (10% vs. 0%; p = 0. 006). Examination of other covariables that may have contributed to wound reoperation revealed the width of the excised skin (WES) to be a significant factor [1% (WES < or = 4 cm) vs. 10% (WES > 4 cm), p = 0. 02]. Bone fracture only occurred in patients receiving BRT (n = 3, 4%), although this was not statistically significant (p = 0.2). The rate of peripheral nerve damage, however, was similar in both arms (7% vs. 7%). CONCLUSION: The overall morbidity associated with adjuvant BRT was not significantly higher than that with surgery alone. However, BRT and WES > 4 cm were associated with significantly higher wound reoperation rate. This has significant implications for strategies designed to maximize wound coverage in patients who receive BRT.

Treatment-plan optimization for soft-tissue sarcoma brachytherapy using a genetic algorithm.

PURPOSE: To describe a treatment-plan optimization system for temporary implant of soft-tissue sarcomas using a genetic algorithm, and evaluate its potential advantages over manual planning. METHODS AND MATERIALS: A planning system that optimizes the distribution of radioactive seeds needed for adequate coverage of the target in the treatment of soft-tissue sarcomas has been designed and implemented. The treatment-planning procedures include simulation, film digitization, target-volume definition, optimized planning, and plan evaluation. The input to the optimization program consists of seed coordinates reconstructed from isocentric films, prescription points, and a list of available seed activities. The optimization is performed using a genetic algorithm. RESULTS: Case studies are presented, which compare plans generated by computer optimization or by trial and error (manually). As expected, computer-optimized plans are often (but not always) superior to manual plans. This is particularly evident for situations where (unavoidably) catheters are far apart or irregularly spaced, in which case the advantages of optimized planning in terms of tumor coverage can be quite dramatic. When the target volume is well contained, the optimized plan minimizes the dose to normal tissue. Computer-based optimization has the additional advantage of being much faster than manual planning; this is valuable because it often reduces the total time the patient will spend in the hospital before implantation. CONCLUSION: Optimized planning with a genetic algorithm and seeds of different activities significantly improves planning efficiency and generally results in improved plan quality. The utility of this optimization system is not limited to sarcoma implants.

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.