Measuring Radiation Toxicity Using Circulating Cell-Free DNA in Prostate Cancer Patients.

BACKGROUND: After radiation therapy (RT), circulating plasma cell-free DNA (cfDNA) released in response to RT damage to tissue can be measured within hours. We examined for a correlation between cfDNA measured during the first week of therapy and early and late gastrointestinal (GI) and genitourinary (GU) toxicity. MATERIAL AND METHODS: Patients were eligible for enrollment if they planned to receive proton or photon RT for nonmetastatic prostate cancer in the setting of an intact prostate or after prostatectomy. Blood was collected before treatment and on sequential treatment days for the first full week of therapy. Toxicity assessments were performed at baseline, weekly during RT, and 6 months and 12 months after RT. Data were analyzed to examine correlations among patient-reported GI and GU toxicities. RESULTS: Fifty-four patients were evaluable for this study. Four (7%) and 3 (6%) patients experienced acute and late grade 2 GI toxicity, respectively. Twenty-two (41%) and 18 (35%) patients experienced acute and late grade 2 GU toxicity, respectively. No patients developed grade 3 or higher toxicity. Grade 2 acute GI toxicity, but not grade 2 acute GU toxicity, was significantly correlated with pre-RT cfDNA levels and on all days 1, 2, 3, 4, and 5 of RT (P < .005). Grade 2 late GI toxicity, but not GU toxicity, was significantly correlated with pre-RT cfDNA levels (P = .021). CONCLUSIONS: Based on this preliminary study, cfDNA levels can potentially predict the subset of patients destined to develop GI toxicity during prostate cancer treatment. Given that the toxicity profiles of the various fractionations and modalities are highly similar, the data support the expectation that cfDNA could provide a biological estimate to complement the dose-volume histogram. A test of this hypothesis is under evaluation in a National Cancer Institute-funded multi-institutional study.

Reirradiation in Conservative Salvage of Recurrent Soft-tissue Sarcoma: An Analysis of Treatment Efficacy and Toxicities.

OBJECTIVE: Compared with radical resection alone, perioperative radiation therapy (RT) combined with neurovascular preserving surgery is the standard for the management of virgin soft-tissue sarcomas. Yet, the optimal management of a local recurrence remains unclear. We report outcomes of patients with locally recurrent soft-tissue sarcoma treated with resection and reirradiation at the University of Florida. MATERIALS AND METHODS: We reviewed the records of patients treated with primary conservative surgery and radiation for soft-tissue sarcoma followed by salvage resection and reirradiation for a local recurrence at our institution. RESULTS: We analyzed 23 patients treated between 1976 and 2014 (median follow-up, 46 mo). Tumor sites included: proximal extremity, 11 patients; trunk, 6; distal extremity, 5; and head and neck, 1. All patients had conservative gross total resection of their recurrent tumor, without amputation. For reirradiation, 16 patients received external-beam RT alone, 6 received external-beam RT and brachytherapy, and 1 received brachytherapy alone. Two patients received chemotherapy. After retreatment, the 5-year overall survival, cause-specific survival, local control, and distant control rates were 39%, 42%, 46%, and 60%, respectively. Ten patients experienced local recurrences, 1 experienced regional recurrence, and 9 developed distant metastases. Retreatment-related complications ranged from delayed wound healing to limb amputation; 8 patients required amputation. Only 3 patients remained disease-free at last follow-up. No statistically significant associations were found between treatment factors (eg, RT dose) and local control. CONCLUSIONS: Achieving local control of recurrent soft-tissue sarcoma is challenging. Treatment with reoperation and reirradiation can lead to debilitating complications affecting function and quality of life.

Circulating Cell-Free DNA Correlates with Body Integral Dose and Radiation Modality in Prostate Cancer.

PURPOSE: The RadTox assay measures circulating cell-free DNA released in response to radiotherapy (RT)-induced tissue damage. The primary objectives for this clinical trial were to determine whether cell-free DNA numbers measured by the RadTox assay are (1) correlated with body integral dose, (2) lower with proton RT compared with photon RT, and (3) higher with larger prostate cancer RT fields. PATIENTS AND METHODS: Patients planned to receive proton or photon RT for nonmetastatic prostate cancer in the setting of an intact prostate or postprostatectomy were eligible for the trial. Plasma was collected pre-RT and at 5 additional daily collection points beginning 24 hours after the initiation of RT. Data from 54 evaluable patients were analyzed to examine any correlations among RadTox scores with body-integral dose, RT modality (photon versus proton), and RT field size (prostate or prostate bed versus whole pelvis). RESULTS: Body integral dose was significantly associated with the peak post-RT RadTox score (P = .04). Patients who received photon RT had a significant increase in peak post-RT RadTox score (P = .04), average post-RT RadTox score (P = .04), and day-2 RadTox score (all minus the pre-RT values for each patient) as compared with patients who received proton RT. Field size was not significantly associated with RadTox score. CONCLUSION: RadTox is correlated with body integral dose and correctly predicts which patients receive proton versus photon RT. Data collection remains ongoing for patient-reported RT toxicity outcomes to determine whether RadTox scores are correlated with toxicity.

Radiation Treatment for Ewing Sarcoma Family of Tumors in Adult Patients: A Single Institution's Experience Over 40 Years.

PURPOSE/OBJECTIVES: To report prognostic factors and long-term outcomes in adults with Ewing sarcoma treated with definitive radiotherapy. MATERIALS AND METHODS: We reviewed patients 18 years old and above with nonmetastatic Ewing sarcoma treated with radiotherapy +/- chemotherapy or surgery. Outcomes were stratified by age (30 and above vs. younger than 30 y), soft tissue extension, tumor size (≥8.5 vs. <8.5 cm), tumor location, resection (yes vs. no), and treatment era (1970-1992 vs. 1993-2012). Toxicities were scored using the RTOG criteria. RESULTS: Fifty-five patients (21 women) were treated with radiotherapy. Average age at diagnosis: 26.7 years (38 patients below 30 vs. 17 patients 30 y and above). A total of 43 had soft tissue extension (78%). Median tumor size: 8.5 cm. Most tumors were in the pelvis (40%), followed by the lower (27%) and upper (24%) extremities. All but 1 patient received chemotherapy; 13 underwent resection. Median dose: 55 Gy. Median follow-up: 3.6 years; 17.5 years for living patients. The 5-year overall (OS) and cause-specific survival (CSS) rates were both 46%. OS and CSS rates were unaffected by age (P=0.97), tumor size (P=0.12), or tumor location (P=0.99). Soft tissue extension portended a significantly poorer prognosis for 5-year OS and CSS: 37% vs. 82% (with and without, respectively; P=0.04). Patients who underwent resection had improved 5-year OS and CSS: 77% vs. 37%, respectively (P=0.01). Patients treated after 1993 had improved 5-year OS: 58% vs. 37% (P=0.0264). CONCLUSIONS: Adult patients with Ewing sarcoma experience similar treatment outcomes regardless of age at diagnosis. Soft tissue extension represents a poor prognostic factor. Aggressive trimodality therapy achieved the highest OS and CSS.

Long-term Tumor Control With Radiotherapy for Symptomatic Hemangioma of a Vertebral Body.

STUDY DESIGN: Retrospective outcomes review. OBJECTIVE: To analyze and report long-term outcomes in a cohort of patients treated with radiotherapy (RT) for symptomatic hemangioma of a vertebral body. SUMMARY OF BACKGROUND DATA: Data are scarce on the rate of tumor control with long-term (>5 yr) follow-up after RT for symptomatic hemangioma of a vertebral body. METHODS: We retrospectively reviewed the medical records of patients treated at our institution between 1971 and 2008 for symptomatic hemangioma of a vertebral body, updated their follow-up, analyzed complications, and calculated the tumor control rate. Tumor control by imaging was defined as no increase in tumor size on computed tomography (CT) or magnetic resonance (MR) scan. Clinical tumor control was defined as no symptoms of recurrent tumor. RESULTS: Ten patients were eligible for analysis. All patients had pain from visible hemangioma at the time of radiotherapy for which surgical resection or interventional radiology procedures were likely to result in high morbidity. Tumors were located in the lumbar (40%), thoracic (50%), or cervical (10%) areas of the spine. The mean radiotherapy dose delivered was 47 Gy.Mean imaging follow-up after completion of radiotherapy was 8.1 years; mean clinical follow-up was 21.2 years. The tumor control rate was 90% (9/10). One patient who may have developed a tumor recurrence had radiographic and clinical evidence of tumor progression 30 years after radiotherapy. The actuarial rate of tumor control was 100% at 5, 10, 20, and 25 years. There was no grade more than or equal to three treatment toxicities, no evidence of malignant transformation, and no evidence of second tumors in treatment area (with the possible exception of the one tumor recurrence). CONCLUSION: RT for symptomatic hemangioma of the spine provides long-term tumor control with a low risk of serious complications. Radiotherapy is a good option when surgery or an interventional radiology procedure is high-risk. Our preferred dose is 45 Gy at 1.8 Gy/fraction. LEVEL OF EVIDENCE: 4.

Treatment of Sarcoma Lung Metastases with Stereotactic Body Radiotherapy.

BACKGROUND: The most common site of sarcoma metastasis is the lung. Surgical resection of pulmonary metastases and chemotherapy are treatment options that have been employed, but many patients are poor candidates for these treatments for multiple host or tumor-related reasons. In this group of patients, radiation might provide a less morbid treatment alternative. We sought to evaluate the efficacy of radiotherapy in the treatment of metastatic sarcoma to the lung. METHODS: Stereotactic body radiotherapy (SBRT) was used to treat 117 pulmonary metastases in 44 patients. Patients were followed with serial computed tomography imaging of the chest. The primary endpoint was failure of control of a pulmonary lesion as measured by continued growth. Radiation-associated complications were recorded. RESULTS: The majority of patients (84%) received a total dose of 50 Gy per metastatic nodule utilizing an image-guided SBRT technique. The median interval follow-up was 14.2 months (range 1.6-98.6 months). Overall survival was 82% at two years and 50% at five years. Of 117 metastatic nodules treated, six nodules showed failure of treatment (95% control rate). Twenty patients (27%) developed new metastatic lesions and underwent further SBRT. The side effects of SBRT included transient radiation pneumonitis (n=6), cough (n=2), rib fracture (n=1), chronic pain (n=1), dermatitis (n=1), and dyspnea (n=1). CONCLUSION: Stereotactic body radiotherapy is an effective and safe treatment for the ablation of pulmonary metastasis from sarcoma. Further work is needed to evaluate the optimal role of SBRT relative to surgery or chemotherapy for treatment of metastatic sarcoma.

Radiation Therapy for Aggressive Fibromatosis: The Association Between Local Control and Age.

PURPOSE: Radiation therapy (RT) is often used in the treatment of unresectable or recurrent aggressive fibromatosis (also known as desmoid tumor) typically with excellent local control. Prior reports have suggested that local control in pediatric patients with aggressive fibromatosis is poor. We aimed to report a long-term single-institution experience with the radiotherapeutic treatment of these tumors with a focus on age-dependent outcomes. METHODS AND MATERIALS: A total of 101 patients treated with RT for aggressive fibromatosis between 1975 and 2015 at a single institution were identified. A variety of demographic and treatment-related variables were abstracted from patients' medical records. Kaplan-Meier analyses were performed to investigate the relationship between these variables and local control. RESULTS: Overall survival was excellent (98% and 95% at 5 and 10 years, respectively); local control was likewise excellent (82% and 78% at 5 and 10 years, respectively). Patients aged <20 years at diagnosis had significantly worse 5-year local control than those aged >40 years at diagnosis (72% vs 97%; hazard ratio, 9.0; P = .009). Patients treated with once-daily fractionation had significantly improved 5-year local control compared with those treated with twice-daily fractionation (90% vs 73%; hazard ratio, 0.3; P = .008). Neither the presence of gross versus microscopic residual disease, initial versus recurrent presentation, number of prior surgical procedures, nor tumor size had any effect on 5-year local control. In a total of 36.6% of patients, Common Terminology Criteria for Adverse Events grade 3 or 4 toxicity developed following treatment; the frequency of toxicities was reduced in patients treated during or after 1995 (24.5%) relative to those treated prior to 1995 (51.9%, P = .02). CONCLUSIONS: RT for aggressive fibromatosis offers excellent local control and should remain the standard of care for patients with unresectable or recurrent disease. Younger patients have diminished local control relative to older patients, suggesting possible biological differences contributing to radioresistance in the pediatric and young adult population.

Stereotactic body radiation therapy for the treatment of oligoprogression on androgen receptor targeted therapy in castration-resistant prostate cancer.

Castration-resistant prostate cancer is an incurable disease. To date, six agents-abiraterone, enzalutamide, docetaxel, cabazitaxel, radium-223 and sipuleucel-T- have shown clinical efficacy in phase III clinical trials, leading to their FDA approval. Patients are typically sequenced through most or all of these agents, and then eventually succumb to their disease. Development of new treatments remains an unmet need. We report a case of a patient who progressed on enzalutamide with a single enlarging metastatic lesion, was treated with ablative stereotactic body radiation therapy while maintaining the same systemic treatment, who then had durable complete remission. Our findings have important clinical implications and suggest novel clinical trials for this difficult to treat disease.

Stereotactic body radiation therapy for oligoprogression of metastatic disease from gastrointestinal cancers: A novel approach to extend chemotherapy efficacy.

Chemotherapy and targeted therapies are effective palliative options for numerous unresectable or metastatic cancers. However, treatment resistance inevitably develops leading to mortality. In a subset of patients, systemic therapy appears to control the majority of tumors leaving 5 or less to progress, a phenomenon described as oligoprogression. Reasoning that the majority of lesions remain responsive to ongoing systemic chemotherapy, we hypothesized that local treatment of the progressing lesions would confer a benefit. The present study describes the cases of 5 patients whose metastatic disease was largely controlled by chemotherapy. The oligoprogressive lesions (≤5) were treated with stereotactic body radiotherapy (SBRT), justifying continued use of an effective systemic regimen. A total of 5 patients with metastatic disease on chemotherapy, with ≤5 progressing lesions amenable to SBRT, were treated with ablative intent. Primary tumor site and histology were as follows: 2 with metastatic colon adenocarcinoma, 2 with metastatic rectal adenocarcinoma and 1 with metastatic pancreatic adenocarcinoma. Imaging was performed prior to SBRT and every 3 months after SBRT. In total, 4 out of the 5 patients achieved disease control for >7 months with SBRT, without changing chemotherapy regimen. The median time to chemotherapy change was 9 months, with a median follow-up time of 9 months. The patient who failed to respond developed progressive disease outside of the SBRT field at 3 months. In conclusion, the addition of SBRT to chemotherapy is an option for the overall systemic control of oligoprogressive disease.

Function Preservation After Conservative Resection and Radiotherapy for Soft-tissue Sarcoma of the Distal Extremity: Utility and Application of the Toronto Extremity Salvage Score (TESS).

OBJECTIVE: To evaluate outcomes after conservative resection and radiotherapy (RT) for soft-tissue sarcoma (STS) of the distal extremity, with assessment of functional quality of life using the validated Toronto Extremity Salvage Score (TESS) questionnaire and Common Terminology Criteria for Adverse Events (CTCAE), v4.0. METHODS: Thirty-three patients with STS involving the hand/wrist (N=18) or foot/ankle (N=15) complex received adjuvant RT with conservative resection and were evaluated for local tumor control, survival, toxicities, and preservation of objective functional ability. Eight patients were treated with preoperative RT (median dose, 50.4 Gy) and 25 with postoperative RT (median dose, 61.8 Gy). Median follow-up was 11.5 years. Functional outcomes were measured using TESS; patients with amputations were excluded from the TESS analysis. Adverse events related to gait, limb edema, skin infection, wound complication, and wound dehiscence were assessed using the CTCAE. RESULTS: The 5- and 10-year local control rates were both 90%. The 10-year cause-specific, absolute, and distant metastasis-free survival rates were 97%, 87%, and 84%, respectively. Three patients had an amputation for reasons other than local recurrence or treatment complications and underwent amputation for patient preference. One third of the subjects (11/33 patients) were able to complete the TESS questionnaire; scores ranged from 88 to 100 (mean, 98.2). CTCAEv4 acute adverse events occurred in 2 cases: 1 patient had a grade 3 skin infection and 1 had a grade 2 wound complication of dehiscence. CONCLUSIONS: For management of distal extremity STS, the combination of adjuvant RT and conservative surgery achieves excellent local control and overall survival with few adverse events. In addition, through application of the TESS survey instrument, we have demonstrated that this treatment plan achieves robust functional preservation objectively and quantifiably.

Treatment of Small Cell Carcinoma of the Bladder With Chemotherapy and Radiation after Transurethral Resection of a Bladder Tumor.

OBJECTIVES: Small cell carcinoma of the bladder is a rare, aggressive cancer with a high potential for metastases. We analyzed outcomes of patients with small cell carcinoma of the bladder treated curatively with chemotherapy and radiotherapy with bladder preservation. MATERIALS AND METHODS: We reviewed the medical records of 11 patients treated with radiotherapy at our institution between 1988 and 2010 for biopsy-proven small cell carcinoma of the bladder clinically localized to the true pelvis. Each patient received transurethral resection of the bladder tumor followed by induction chemotherapy and consolidative radiation or concurrent chemoradiation. After completing radiotherapy, cystoscopy was performed to evaluate local response. Overall survival, distant metastasis-free survival, local-regional control, and complete response rates are reported. RESULTS: The median follow-up was 1.1 years for all patients and 10 years for survivors. Nine patients had clinical T3-T4 disease and 3 had node-positive disease. All patients were treated with conventional radiotherapy (median dose, 59 Gy) and cisplatin-based chemotherapy. Eight patients had a cystoscopy after completing chemoradiation, all of whom had a biopsy-proven complete response. The remaining 3 patients developed a distant metastasis before cystoscopy could be performed. The 3-year overall survival rate was 24%; the distant metastasis-free survival rate was 27%; and the local-regional control rate was 78%. All patients who achieved local control maintained functioning bladders. No Common Terminology Criteria for Adverse Events toxicity scale, version 3.0 late grade 3 genitourinary or gastrointestinal toxicities occurred. CONCLUSIONS: Primary chemoradiation provides reasonable local-regional control rates with a functioning bladder, even for patients with locally advanced disease, and is an effective alternative to cystectomy when aiming for bladder conservation.

New primary malignancy masquerading as metastatic prostate adenocarcinoma.

In the management of patients with prostate cancer, the development of new radiographic findings can mimic progression of the disease, thereby triggering changes in treatment. Typically, clinicians evaluate additional parameters, such as symptoms and prostate specific antigen (PSA) levels, for further evidence of disease progression. In the absence of additional findings, for example, elevated PSA, the possibility of an additional malignancy should be considered and evaluated. We present three cases of patients undergoing treatment for prostate adenocarcinoma and discovered on imaging to have findings suggestive of disease progression, but ultimately found to be a new primary malignancy. Our cases suggest that, in patients with prostate cancer, the appearance of new lymphadenopathy or bone lesions cannot be assumed to solely represent progression of the prostate cancer and warrant further investigation, especially in the presence of stable PSA levels.

Multidisciplinary neoadjuvant management for potentially curable pancreatic cancer.

Pancreatic adenocarcinoma remains the fourth leading cause of cancer mortality in the U.S. Despite advances in surgical technique, radiotherapy technologies, and chemotherapeutics, the 5-year survival rate remains approximately 20% for the 15% of patients who are eligible for surgical resection. The majority of this group suffers metastatic recurrence. However, despite advances in therapies for patients with advanced pancreatic cancer, only surgery has consistently proven to improve long-term survival. Various combinations of chemotherapy, biologic-targeted therapy, and radiotherapy have been evaluated in different settings to improve outcomes. In this context, a neoadjuvant (preoperative) treatment strategy offers numerous potential benefits: (1) ensuring delivery of early, systemic therapy, (2) improving selection of patients for surgical therapy with truly localized disease, (3) potential downstaging of the neoplasm facilitating a negative margin resection in patients with locally advanced disease, and (4) providing a superior clinical trial mechanism capable of rapid assessment of the efficacy of novel therapeutics. This article reviews the recent trends in the management of pancreatic adenocarcinoma, with a particular emphasis on a multidisciplinary neoadjuvant approach to treatment.

Multidisciplinary management of soft tissue sarcoma.

Soft tissue sarcoma is a rare malignancy, with approximately 11,000 cases per year encountered in the United States. It is primarily encountered in adults but can affect patients of any age. There are many histologic subtypes and the malignancy can be low or high grade. Appropriate staging work up includes a physical exam, advanced imaging, and a carefully planned biopsy. This information is then used to guide the discussion of definitive treatment of the tumor which typically involves surgical resection with a negative margin in addition to neoadjuvant or adjuvant external beam radiation. Advances in imaging and radiation therapy have made limb salvage surgery the standard of care, with local control rates greater than 90% in most modern series. Currently, the role of chemotherapy is not well defined and this treatment is typically reserved for patients with metastatic or recurrent disease and for certain histologic subtypes. The goal of this paper is to review the current state of the art in multidisciplinary management of soft tissue sarcoma.

Radiotherapy in the management of giant cell tumor of bone.

OBJECTIVES: To evaluate the long-term treatment outcomes for patients with giant cell tumor of bone (GCTB) treated with radiotherapy with or without surgical resection. METHODS: This retrospective review includes 34 patients with GCTB treated with megavoltage radiotherapy between January 1973 and January 2008 at the University of Florida. Patients' ages ranged from 16 to 85 years (median, 29). Tumor sizes ranges from 2.5 to 12 cm (median, 4.8 cm) in the maximum dimension. Twenty-one patients received radiation for gross disease, either de novo (22 patients) or recurrent (12 patients). Thirteen patients were treated with postoperative radiation after gross total resection. The median dose was 45 Gy in both the definitive and adjuvant settings. RESULTS: The median follow-up was 16.8 years. The 5- and 10-year local-control (LC) rates were 85% and 81%, respectively. Six patients developed an isolated local recurrence (2/13 treated postoperatively and 4/21 who were treated for gross disease). All 6 patients who developed a local recurrence were successfully salvaged with surgery; therefore, the ultimate LC rate was 100%. Both the 5- and 10-year freedom from distant metastasis rates were 91%. Three patients developed lung metastases, including 1 patient who experienced GCTB transformation into a high-grade sarcoma. The 5- and 10-year progression-free survival rates were both 78%. CONCLUSIONS: Moderate-dose radiotherapy for GCTB provides a long-term LC >80%, justifying its role as an alternative to morbid surgery.

Radiotherapy for spermatic cord sarcoma.

OBJECTIVES: Spermatic cord sarcomas are rare paratesticular tumors affecting older men. Current management is based on small series, case reports, and literature reviews, with surgery still the mainstay of treatment. Local-regional recurrence is common after definitive surgery (~50%), but patients treated with adjuvant radiotherapy may have improved outcomes. METHODS: We reviewed the outcomes of 15 patients with intermediate-grade to high-grade spermatic cord sarcomas treated with radiation at our institution from 1974 to 2009. Patients were treated to 40 to 60 Gy using conformal opposed anterior-posterior/posterior-anterior ports to the scrotum, inguinal canal, and lower pelvic wall with various beam energies. Some patients were managed with surgical exploration and resection, followed by radiotherapy and/or definitive surgery. More recently treated patients had an initial biopsy, followed by preoperative radiation or planned resection with postoperative radiation therapy. RESULTS: No patient experienced a local recurrence. Two patients had regional nodal recurrences and 1 had distant metastases. All recurrences were in patients who had initial "exploration" with unexpected findings of sarcoma during surgery versus planned, definitive resection with planned adjuvant radiotherapy. At 5 years, overall survival was 53%, but cause-specific survival was 80%. Complications were minimal, with only 4 grade 2 or 3 toxicities and no grade 4 toxicities. CONCLUSIONS: Although most patients die from causes other than disease progression, this sarcoma carries grave morbidity. Optimizing the primary management is of utmost importance. Unplanned treatments complicate definitive therapy and increase the risk of local-regional contamination and recurrence. Proactive management is therefore consistent with sarcomas of other primary sites, ideally with preoperative radiotherapy and definitive resection.

Long-term treatment outcomes for patients with synovial sarcoma: a 40-year experience at the University of Florida.

OBJECTIVES: The objective of the study was to evaluate our long-term outcomes and prognostic factors for patients treated for localized synovial sarcoma. METHODS: We retrospectively reviewed the medical records of 92 patients treated for nonmetastatic synovial sarcoma at the University of Florida from 1967 to 2007. Most patients were treated with limb-sparing surgery and radiation (63%), 27% received surgery alone and 10% received radiation only as definitive treatment. Among patients treated with surgery and radiation, 69% received preoperative radiation and 31% received postoperative radiation. RESULTS: Median follow-up of living patients was 12.5 years. Overall survival rates at 5 and 10 years were 61% and 56%, respectively. Progression-free survival rates were 56% and 53%, respectively. Local control (LC) rates at 5 and 10 years were 90% and 88%, respectively. Freedom from distant metastasis rates were 57% at 5 years and 55% at 10 years. The severe complication (requiring surgery) rate was 13%. Size >5 cm predicted worse overall survival, progression-free survival, and freedom from distant metastasis, but not LC. No other prognostic factor was significant on multivariate analysis. CONCLUSIONS: Selectively adding radiotherapy to surgery results in excellent LC for these patients. However, distant metastasis remains the principal factor limiting survival and seems directly related to primary tumor size at presentation.

Transanal excision with radiation therapy for rectal adenocarcinoma.

OBJECTIVE: To evaluate the efficacy of transanal excision (TAE) combined with radiotherapy for rectal adenocarcinoma, assess the ability of pretreatment endoscopic ultrasound (EUS) to predict failures, and determine the prognostic value of downstaging and complete pathological response. DESIGN: Retrospective outcomes study. SETTING: Radiation oncology clinic. PARTICIPANTS: Thirty-eight patients with rectal adenocarcinoma. METHODS: The medical records of patients treated with radiotherapy from 1998 to 2008 and followed for a median of 5.9 years were reviewed. RESULTS: Kaplan-Meier estimates of freedom from selected endpoints at 5 years after treatment were: overall survival, 79%; cause-specific survival, 91%; local control, 90%; and freedom from distant metastasis, 76%. Seven patients (21%) had eventual abdominoperineal resection or lower anterior resection, four patients had local recurrence, and three patients had incomplete treatment or poor margins. T3 lesions clinically staged by EUS were a predictor of local failure (P=0.0110), but not distant metastasis (P=0.35). Patients with either a pathological or clinical T3 lesion did not have a significantly greater rate of metastasis (P=0.096). Patients who were downstaged did not have a significantly different rate of local recurrence or metastasis. Patients who experienced a complete pathological response did not have a significantly different rate of local control or distant metastasis. CONCLUSION: Patients with early-stage rectal lesions who undergo preoperative or postoperative radiation and TAE have similar outcomes to those who undergo abdominoperineal resection; local recurrence was higher for patients with T3 lesions when both were compared. Abdominal surgery should be considered for these patients. TAE is reasonable when patients are unwilling or unable to tolerate the morbidity of traditional transabdominal surgery.

Long-term results following postoperative radiotherapy for soft tissue sarcomas of the extremity.

PURPOSE: To review long-term outcomes following postoperative radiotherapy (RT) for extremity soft tissue sarcoma (STS) and identify variables affecting the therapeutic ratio. METHODS AND MATERIALS: Between 1970 and 2008, 173 patients with localized extremity STS were treated with postoperative radiation. No patients received prior irradiation. Sixteen percent of tumors had recurred after initial surgery alone; 89% of tumors were high grade. The median patient age was 57 years (range, 18-86 years). Sixty-one percent underwent >1 surgery before RT in an attempt to achieve wide negative margins. Final margin status was negative in 70% and marginal or microscopically positive in 30%. The median time between final surgery and start of RT was 40 days. The median RT dose was 65 Gy (range, 49-74 Gy). The median follow-up for all patients was 10.4 years and 13.2 years among survivors. RESULTS: At 10 years, local control (LC), cause-specific survival (CSS), and overall survival (OS) rates were 87%, 80%, and 70%, respectively, with 89% of local failures occurring within 3 years after treatment. On multivariate analysis, age >55 years (82% vs 93%, P<.05) and recurrent presentation (67% vs 91%, P<.05) were associated with inferior 10-year LC. The LC according to final margin status was 90% for wide negative margins vs 79% for marginal/microscopically positive margins (P=.08). Age>55 years and local recurrence were associated with inferior CSS and OS on multivariate analysis. Twelve percent of patients experienced grade 3+ toxicity; 12 of these occurred in patients with tumors of the proximal lower extremity, with the most common toxicity of pathologic fracture occurring in 6.3%. CONCLUSIONS: This large single-institution series confirms that postoperative RT for STS of the extremities provides good long-term disease control with acceptable toxicity. Our experience supports recurrent presentation and older age as adverse prognostic factors for LC.