Stage I and II Endometrial Adenocarcinoma: Analysis of 2009 FIGO Staging Revision and Impact on Survival by Adjuvant Therapy.

BACKGROUND: In 2009, the International Federation of Gynecology and Obstetrics revised the staging classification for endometrial cancer. Mucosal cervical involvement was eliminated from the criteria and only those with stromal cervical involvement were considered stage II. We examined the implications of the staging changes and the survival impact of adjuvant therapy in stage I to II endometrial adenocarcinoma. MATERIALS AND METHODS: Data were obtained from the National Oncology Data Alliance. Stage I to II endometrial adenocarcinoma patients diagnosed between 1988 and 2008 were identified and grouped according to the 1988 International Federation of Gynecology and Obstetrics staging. Multivariate analysis (MVA) was performed using proportional hazards model; comparison of Kaplan-Meier survival curves was based on the log-rank statistic. RESULTS: A total of 14,158 patients with stage I to II endometrial adenocarcinoma were identified with a median follow-up of 41 months. Adjuvant external-beam radiation therapy (EBRT) and adjuvant vaginal brachytherapy (VB) were positive predictors for overall survival (OS) only in IC, IIA, and IIB. On MVA, stages IA and IB OS did not differ (P=0.17), IIA had worse OS compared with IC (P<0.05), and IIA OS did not differ from IIB (P=0.57). Neither IA nor IB benefited from adjuvant radiotherapy on MVA. However, both IC and IIA had OS improvements with VB±EBRT (P<0.05) with the greatest impact from the VB. CONCLUSIONS: Mucosal cervical involvement represents a risk factor and should be considered when determining adjuvant therapy. Adjuvant therapy provided no survival benefit in 1988 stage IA or IB; however, adjuvant radiotherapy is recommended in the management of IC, IIA, and IIB.

The use of dose-escalated radiation for locally advanced non-small cell lung cancer in the U.S., 2004-2013.

PURPOSE/OBJECTIVES: The clinical effects of radiation dose-intensification in locally advanced non-small cell lung (NSCLCa) and other cancers are challenging to predict and are ideally studied in randomized trials. The purpose of this study was to assess the use of dose-escalated radiation for locally advanced NSCLCa in the U.S., 2004-2013, a period in which there were no published level 1 studies on dose-escalation. MATERIALS/METHODS: We performed analyses on two cancer registry databases with complementary strengths and weaknesses: the National Oncology Data Alliance (NODA) 2004-2013 and the National Cancer Database (NCDB) 2004-2012. We classified locally advanced patients according to the use of dose-escalation (>70 Gy). We used adjusted logistic regression to assess the association of year of treatment with dose-escalated radiation use in two periods representing time before and after the closure of a cooperative group trial (RTOG 0617) on dose-escalation: 2004-2010 and 2010-2013. To determine the year in which a significant change in dose could have been detected had dose been prospectively monitored within the NODA network, we compared the average annual radiation dose per year with the forecasted dose (average of the prior 3 years) adjusted for patient age and comorbidities. RESULTS: Within both the NODA and NCDB, use of dose-escalation increased from 2004 to 2010 (p < 0.0001) and decreased from 2010 to 2013 (p = 0.0018), even after controlling for potential confounders. Had the NODA network been monitoring radiation dose in this cohort, significant changes in average annual dose would have been detected at the end of 2008 and 2012. CONCLUSIONS: Patterns of radiation dosing in locally advanced NSCLCa changed in the U.S. in the absence of level 1 evidence. Monitoring radiation dose is feasible using an existing national cancer registry data collection infrastructure.

Estimation of radiation-induced secondary cancer risks for early-stage non-small cell lung cancer patients after stereotactic body radiation therapy.

PURPOSE: In this study, we evaluated radiation-induced secondary lung cancer risks for the lung and the breast from stereotactic body radiation therapy treatment of early-stage non-small cell lung cancer with different radiation therapy treatment modalities. METHODS AND MATERIALS: Ten patients (5 men and 5 women) with early-stage non-small cell lung cancer who received definitive stereotactic body radiation therapy treatments were retrospectively selected. For each patient, two 3-dimensional conformal radiation therapy (3D-CRT) plans using 6- and 10-MV photons, respectively; a helical tomotherapy (HT) plan; and 2 volumetric modulated arc therapy (VMAT) plans using 1 and 2 arcs, respectively, were generated. The excess absolute risk (EAR) for secondary cancer occurrence was calculated using 3 organ equivalent dose models: the linear-exponential model, the plateau model, and the linear model for prescription dose range of 30 to 70 Gy. RESULTS: The 3D-CRT plans showed significantly lower monitor units compared with the rotational intensity modulate radiation therapy plans. Based on each of the 3 organ equivalent dose models, HT and VMAT plans showed comparable average EARs to both the lung and the breast compared with the 3D-CRT plans in the prescription dose range of 30 to 70 Gy. At a prescription dose of 50 Gy and using the linear-exponential model, the average lung EAR estimation ranged from 15.7 ± 5.3 to 16.0 ± 6.5 per 10,000 patients per year with the 5 delivery techniques, and the average EAR estimation for the breast ranged from 18.0 ± 14.0 to 21.0 ± 15.0 per 10,000 patients per year. The secondary cancer risk increased approximately linearly with mean organ dose. The 3D-CRT plans showed significantly higher secondary cancer risk for the ipsilateral lung and lower risk for the contralateral lung compared with the HT and VMAT plans. CONCLUSIONS: Rotational intensity modulate radiation therapy techniques including helical tomotherapy and VMAT do not increase secondary cancer risks for the lung or the breast compared with 3D-CRT techniques, despite higher monitor units used.

Effect of increasing radiation dose on pathologic complete response in rectal cancer patients treated with neoadjuvant chemoradiation therapy.

BACKGROUND: Neoadjuvant chemoradiation therapy (CRT) increases pathological complete response (pCR) rates compared to radiotherapy alone in patients with stage II-III rectal cancer. Limited evidence addresses whether radiotherapy dose escalation further improves pCR rates. Our purpose is to measure the effects of radiotherapy dose and other factors on post-therapy pathologic tumor (ypT) and nodal stage in rectal cancer patients treated with neoadjuvant CRT followed by mesorectal excision. MATERIAL AND METHODS: A non-randomized comparative effectiveness analysis was performed of rectal cancer patients treated in 2000-2013 from the National Oncology Data Alliance™ (NODA), a pooled database of cancer registries from >150 US hospitals. The NODA contains the same data submitted to state cancer registries and SEER combined with validated radiotherapy and chemotherapy records. Eligible patients were treated with neoadjuvant CRT followed by proctectomy and had complete data on treatment start dates, radiotherapy dose, clinical tumor (cT) and ypT stage, and number of positive nodes at surgery (n = 3298 patients). Multivariable logistic regression was used to assess the predictive value of independent variables on achieving a pCR. RESULTS: On multivariable regression, radiotherapy dose, cT stage, and time interval between CRT and surgery were significant predictors of achieving a pCR. After adjusting for the effect of other variates, patients treated with higher radiotherapy doses were also more likely to have negative nodes at surgery and be downstaged from cT3-T4 and/or node positive disease to ypT0-T2N0 after neoadjuvant CRT. CONCLUSION: Our study suggests that increasing dose significantly improved pCR rates and downstaging in rectal cancer patients treated with neoadjuvant CRT followed by surgery.

Definitive chemotherapy and radiotherapy in patients with stage II non-small cell lung cancer: A population-based outcomes study.

OBJECTIVES: There is a paucity of data on non-surgical outcomes specific to stage II non-small cell lung cancer (NSCLC) patients receiving definitive chemotherapy and radiation therapy (CRT). This study reports population-based outcomes for this subgroup, and investigates a radiation dose-response for overall survival. MATERIALS AND METHODS: The National Oncology Data Alliance (NODA), a merging of multiple tumor registries maintained by Elekta(®) medical systems, was queried for stage II patients and CRT. Only curative cases (RT doses ≥59 Gy) were included. Both sequential and concurrent CRT were allowed. Univariate and Cox multivariate techniques were used to assess factors significant for overall survival. These factors included: gender, age, race, radiation dose, radiation total treatment time, stage, histology, tumor size, and chemotherapy sequence. RESULTS: A total of 568 patients were included in the analysis, with a median follow-up of 12.9 months for surviving patients. Patients were treated between 2004 and 2014. Median survival was 20.5 months (95% confidence interval (CI) 18-23 months), with 16% patients alive at 5 years. Only gender was found to be significantly associated with survival in the Cox model. Although median survival was higher in patients receiving greater than 60 Gy (21 months, 95% CI 18-24 moths) compared to 59-60 Gy (16.5 months 95% CI 10-23 months), this was not statistically significant (p=0.6). CONCLUSIONS: This is the first report on outcomes for stage II NSCLC patients receiving CRT as definitive therapy. Survival approximates stage III CRT patients from historical phase III trials. As an increasing aging population may parallel a rise in medically inoperable stage II patients, this study can provide useful information when reviewing treatment options.

The impact of increasing dose on overall survival in prostate cancer.

PURPOSE: To assess the impact of increasing dose on overall survival (OS) for prostate cancer patients. METHODS: Treatment data were obtained on more than 20,000 patients in the National Oncology Data Alliance®, a proprietary database of merged tumor registries, who were treated for prostate cancer with definitive radiotherapy between 1995 and 2006. Eligible patients had complete data on total dose, T stage, use and timing of androgen deprivation therapy (ADT), and treatment start date (n = 20,028). Patients with prior malignancies were excluded. RESULTS: On multivariate analysis, dose, T stage, grade, marital status, age, and neoadjuvant ADT were significant predictors of OS. Hazard ratios for OS declined monotonically with increasing dose, reaching 0.63 (95 % Confidence Interval 0.53-0.76) at ≥80 Gy. On subset analysis, neoadjuvant ADT significantly improved OS in high risk patients but was not significant in lower risk patients. The dose response was maintained across all risk groups. Medical comorbidities were balanced across all dose strata and sensitivity analysis demonstrated that other prognostic factors were unlikely to explain the observed dose response. CONCLUSIONS: This study suggests that increasing dose significantly improves OS in prostate cancer patients treated with radiotherapy.

Impact of Total Lymph Node Count on Staging and Survival After Neoadjuvant Chemoradiation Therapy for Rectal Cancer.

PURPOSE: Current guidelines recommend that a minimum of 12 lymph nodes (LNs) be dissected to accurately stage rectal cancer patients. Neoadjuvant chemoradiation therapy (CRT) decreases the number of LNs retrieved at surgery. The purpose of this study was to assess the impact of the number of LNs dissected on overall survival (OS) for localized rectal cancer patients treated with neoadjuvant CRT. METHODS: Treatment data were obtained on all patients treated for rectal cancer (2000-2013) in the National Oncology Data Alliance™, a proprietary database of merged tumor registries. Eligible patients were treated with neoadjuvant CRT followed by surgery and had complete data on number of positive LNs, number of LNs examined, and treatment dates (n = 4565). RESULTS: Hazard ratios for OS decreased sequentially with increasing number of LNs examined until a maximum benefit was achieved with examination of eight LNs. On multivariate analysis, age, sex, race, marital status, grade, ypT stage, ypN stage, type of surgery, margin status, presence of pathologically confirmed metastasis at surgery, and number of LNs examined were significant predictors of OS. CONCLUSIONS: Examination of eight or more LNs in rectal cancer patients treated with neoadjuvant CRT resulted in accurate staging and assignment into prognostic groups with an ensuing improvement in OS by stage. This study suggests that eight LNs is the threshold for an adequate lymph node dissection after neoadjuvant CRT.

Dose response for radiation cataractogenesis: a meta-regression of hematopoietic stem cell transplantation regimens.

PURPOSE/OBJECTIVE(S): To perform a meta-regression on published data and to model the 5-year probability of cataract development after hematopoietic stem cell transplantation (HSCT) with and without total body irradiation (TBI). METHODS AND MATERIALS: Eligible studies reporting cataract incidence after HSCT with TBI were identified by a PubMed search. Seventeen publications provided complete information on radiation dose schedule, fractionation, dose rate, and actuarial cataract incidence. Chemotherapy-only regimens were included as zero radiation dose regimens. Multivariate meta-regression with a weighted generalized linear model was used to model the 5-year cataract incidence and contributory factors. RESULTS: Data from 1386 patients in 21 series were included for analysis. TBI was administered to a total dose of 0 to 15.75 Gy with single or fractionated schedules with a dose rate of 0.04 to 0.16 Gy/min. Factors significantly associated with 5-year cataract incidence were dose, dose times dose per fraction (D•dpf), pediatric versus adult status, and the absence of an ophthalmologist as an author. Dose rate, graft versus host disease, steroid use, hyperfractionation, and number of fractions were not significant. Five-fold internal cross-validation showed a model validity of 83% ± 8%. Regression diagnostics showed no evidence of lack-of-fit and no patterns in the studentized residuals. The α/ß ratio from the linear quadratic model, estimated as the ratio of the coefficients for dose and D•dpf, was 0.76 Gy (95% confidence interval [CI], 0.05-1.55). The odds ratio for pediatric patients was 2.8 (95% CI, 1.7-4.6) relative to adults. CONCLUSIONS: Dose, D•dpf, pediatric status, and regimented follow-up care by an ophthalmologist were predictive of 5-year cataract incidence after HSCT. The low α/ß ratio indicates the importance of fractionation in reducing cataracts. Dose rate effects have been observed in single institution studies but not in the combined data analyzed here. Although data were limited to articles with 5-year actuarial estimates, the development of radiation-induced cataracts extends beyond this time.

Effect of CT contrast on volumetric arc therapy planning (RapidArc and helical tomotherapy) for head and neck cancer.

The objectives of the study were to evaluate the effect of intravenous contrast in the dosimetry of helical tomotherapy and RapidArc treatment for head and neck cancer and determine if it is acceptable during the computed tomography (CT) simulation to acquire only CT with contrast for treatment planning of head and neck cancer. Overall, 5 patients with head and neck cancer (4 men and 1 woman) treated on helical tomotherapy were analyzed retrospectively. For each patient, 2 consecutive CT scans were performed. The first CT set was scanned before the contrast injection and secondary study set was scanned 45 seconds after contrast. The 2 CTs were autoregistered using the same Digital Imaging and Communications in Medicine coordinates. Tomotherapy and RapidArc plans were generated on 1 CT data set and subsequently copied to the second CT set. Dose calculation was performed, and dose difference was analyzed to evaluate the influence of intravenous contrast media. The dose matrix used for comparison included mean, minimum and maximum doses of planning target volume (PTV), PTV dose coverage, and V45Gy, V30Gy, and V20Gy organ doses. Treatment planning on contrasted images generally showed a lower dose to both organs and target than plans on noncontrasted images. The doses for the points of interest placed in the organs and target rarely changed more than 2% in any patient. In conclusion, treatment planning using a contrasted image had insignificant effect on the dose to the organs and targets. In our opinion, only CT with contrast needs to be acquired during the CT simulation for head and neck cancer. Dose calculations performed on contrasted images can potentially underestimate the delivery dose slightly. However, the errors of planning on a contrasted image should not affect the result in clinically significant way.

Extramedullary relapse following total marrow and lymphoid irradiation in patients undergoing allogeneic hematopoietic cell transplantation.

PURPOSE: Approximately 5% to 20% of patients who undergo total body irradiation (TBI) in preparation for hematopoietic cell transplantation (HCT) can develop extramedullary (EM) relapse. Whereas total marrow and lymphoid irradiation (TMLI) provides a more conformally targeted radiation therapy for patients, organ sparing has the potential to place the patient at a higher risk for EM relapse than TBI. This study evaluated EM relapse in patients treated with TMLI at our institution. METHODS AND MATERIALS: Patients eligible for analysis had been enrolled in 1 of 3 prospective TMLI trials between 2006 and 2012. The TMLI targeted bones, major lymph node chains, liver, spleen, testes, and brain, using image-guided tomotherapy with total dose ranging from 12 to 15 Gy. RESULTS: A total of 101 patients with a median age of 47 years were studied. The median follow-up was 12.8 months. Incidence of EM relapse and bone marrow (BM) relapse were 12.9% and 25.7%, respectively. Of the 13 patients who had EM relapse, 4 also had BM relapse, and 7 had EM disease prior to HCT. There were a total of 19 EM relapse sites as the site of initial recurrence: 11 soft tissue, 6 lymph node, 2 skin. Nine of these sites were within the target region and received ≥12 Gy. Ten initial EM relapse sites were outside of the target region: 5 sites received 10.1 to 11.4 Gy while 5 sites received <10 Gy. Pretransplantation EM was the only significant predictor of subsequent EM relapse. The cumulative incidence of EM relapse was 4% at 1 year and 11.4% at 2 years. CONCLUSIONS: EM relapse incidence was as frequent in regions receiving ≥10 Gy as those receiving <10 Gy. EM relapse rates following TMLI that included HCT regimens were comparable to published results with regimens including TBI and suggest that TMLI is not associated with an increased EM relapse risk.

Treatment outcomes for patients with chloroma receiving radiation therapy.

INTRODUCTION: This study aims to analyse treatment outcomes, disease control and toxicity in patients with chloromas referred for radiation therapy (RT). METHODS: Medical records were retrospectively reviewed for 41 patients with chloromas treated with RT at our institution. RESULTS: Twenty-five patients were treated with palliative intent, whereas sixteen received RT as a component of curative intent therapy in addition to systemic chemotherapy with or without haematopoietic stem cell transplant (HSCT). All patients received RT for chloroma (median dose 24 Gy). Median survival was 5.4 months after RT (95% confidence interval (CI) 3.5-12.6 months), and no significant difference in overall survival was identified based on prior treatment with systemic chemotherapy alone or HSCT. Patients treated with curative intent had a median survival of 26.2 months (95% CI 6.1-48.9 months) and a Kaplan-Meier estimate of 15% overall survival at 5 years. At the end of the study follow-up period, 38 patients were dead and three patients treated with curative intent remained alive. After palliative RT, 44% of patients experienced partial relief and 48% experienced complete symptomatic improvement without significant acute toxicities. CONCLUSIONS: RT provides timely symptom palliation for patients with chloromas with minimal morbidity, but the prognosis remains poor. Long-term remission can be achieved in selected patients with salvage chemotherapy and HSCT.

Clinical outcomes of patients treated with a second course of stereotactic radiosurgery for locally or regionally recurrent brain metastases after prior stereotactic radiosurgery.

Patients with metastatic disease are living longer and may be confronted with locally or regionally recurrent brain metastases (BM) after prior stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT). This study analyzes outcomes in patients without prior whole brain radiotherapy (WBRT) who were treated with a second course of SRS/FSRT for locally or regionally recurrent BM. We identified 32 patients at our institution who were treated with a second course of SRS/FSRT after initial SRS/FSRT for newly diagnosed BM. We report clinical outcomes including local control, survival, and toxicities. Control rates and survival were calculated using Kaplan-Meier analysis and the multivariate proportional hazards model. The Kaplan-Meier estimate of local control at 6 months was 77 % for targets treated by a second course of SRS/FSRT with 11/71 (15 %) targets experiencing local failure. Multivariate analysis shows that upon re-treatment, local recurrences were more likely to fail than regional recurrences (OR 8.8, p = 0.02). Median survival for all patients from first SRS/FSRT was 14.6 months (5.3-72.2 months) and 7.9 months (0.7-61.1 months) from second SRS/FSRT. Thirty-eight percent of patients ultimately received WBRT as salvage therapy after the second SRS/FSRT. Seventy-one percent of patients died without active neurologic symptoms. The present study demonstrates that the majority of patients who progress after SRS/FSRT for newly diagnosed BM are candidates for salvage SRS/FSRT. By reserving WBRT for later salvage, we believe that a significant proportion of patients can avoid WBRT all together, thus putting fewer patients at risk for neurocognitive toxicity.

Distance-to-agreement investigation of Tomotherapy's bony anatomy-based autoregistration and planning target volume contour-based optimization.

PURPOSE: To compare Tomotherapy's megavoltage computed tomography bony anatomy autoregistration with the best achievable registration, assuming no deformation and perfect knowledge of planning target volume (PTV) location. METHODS AND MATERIALS: Distance-to-agreement (DTA) of the PTV was determined by applying a rigid-body shift to the PTV region of interest of the prostate from its reference position, assuming no deformations. Planning target volume region of interest of the prostate was extracted from the patient archives. The reference position was set by the 6 degrees of freedom (dof)-x, y, z, roll, pitch, and yaw-optimization results from the previous study at this institution. The DTA and the compensating parameters were calculated by the shift of the PTV from the reference 6-dof to the 4-dof-x, y, z, and roll-optimization. In this study, the effectiveness of Tomotherapy's 4-dof bony anatomy-based autoregistration was compared with the idealized 4-dof PTV contour-based optimization. RESULTS: The maximum DTA (maxDTA) of the bony anatomy-based autoregistration was 3.2 ± 1.9 mm, with the maximum value of 8.0 mm. The maxDTA of the contour-based optimization was 1.8 ± 1.3 mm, with the maximum value of 5.7 mm. Comparison of Pearson correlation of the compensating parameters between the 2 4-dof optimization algorithms shows that there is a small but statistically significant correlation in y and z (0.236 and 0.300, respectively), whereas there is very weak correlation in x and roll (0.062 and 0.025, respectively). CONCLUSIONS: We find that there is an average improvement of approximately 1 mm in terms of maxDTA on the PTV going from 4-dof bony anatomy-based autoregistration to the 4-dof contour-based optimization. Pearson correlation analysis of the 2 4-dof optimizations suggests that uncertainties due to deformation and inadequate resolution account for much of the compensating parameters, but pitch variation also makes a statistically significant contribution.

Residual setup errors and dose variations with less-than-daily image guided patient setup in external beam radiotherapy for esophageal cancer.

BACKGROUND AND PURPOSE: To evaluate residual patient setup errors and daily dose variations of different less-than-daily image guidance (IG) strategies in the delivery of external beam radiotherapy for esophageal cancer. MATERIAL AND METHODS: Daily image-guided setup data for 25 consecutive esophageal cancer patients treated with helical tomotherapy were evaluated. Seven less-than-daily IG strategies with different imaging frequencies were simulated. For each IG strategy, the daily residual setup errors were calculated. Using TomoTherapy Planned Adaptive software, daily dose variations to the clinical target volume, heart, and lungs were evaluated in five representative patients. RESULTS: With 0% (60%) IG frequency, the margins required for adequate coverage of the clinical target volume were 13 mm (10 mm), 14 mm (11 mm), and 5 mm (5 mm) in the left-right, superior-inferior, and anterior-posterior directions, respectively. Even with 60% IG frequency, 10% of the fractions had more than 10% decrease in the dose level covering 95% of the target, and 14% and 13% of the fractions had more than 10% increase in total lung volume receiving at least 0.8 Gy per fraction, and heart volume receiving at least 1.2 Gy per fraction, respectively. CONCLUSION: Substantial residual setup errors would occur for treatment fractions without IG even if the most frequent less-than-daily IG strategy was to be used, which could lead to significant daily dose variations for the target volume and adjacent normal tissues. Daily image guidance is recommended throughout the course of treatment in conformal radiotherapy for esophageal cancer.

Repair of radiation damage and radiation injury to the spinal cord.

Radiation myelopathy is a rare but devastating injury to the spinal cord that usually results from an excessive radiation dose. In this chapter, we discuss the traditional and current understandings of the pathogenesis of this injury. A distinction is made between radiation damage, which occurs at the subcellular level, and radiation injury, which occurs at the tissue and organ level in response to radiation damage. Recent findings regarding the amelioration and treatment of both radiation damage and radiation injury are explored. These studies are promising developments but, as always, there are attendant caveats.

Preoperative versus postoperative radiotherapy in soft-tissue sarcoma: multi-institutional analysis of 821 patients.

PURPOSE: To assess the impact of radiotherapy (RT) sequencing with surgery on overall survival (OS), cause-specific survival (CSS), local failure, and distant failure in soft-tissue sarcoma (STS). METHODS AND MATERIALS: A retrospective analysis was conducted using the National Oncology Database, a proprietary database of aggregated tumor registries owned by IMPAC Medical Systems (Sunnyvale, CA). Patients with STS of all major anatomic sites who received definitive surgery and either preoperative (preop) or postoperative (postop) RT were included. Patients were also required to have known stage and grade. Prognostic factors for survival were identified using multivariate techniques. Survival was calculated using the Kaplan-Meier method, and compared for statistical significance (p < 0.05) using the log-rank test. RESULTS: A total of 821 patients met inclusion criteria. The median follow-up time was 63 months. Age, stage, histology, gender, tumor size, and RT sequence were independent predictors for OS (p < 0.05). Preop RT was associated with significantly improved OS and CSS compared with postop RT (hazard ratio [HR] = 0.72, 95% confidence interval [CI] 0.56-0.91, p < 0.01, and HR = 0.64, 95% CI 0.46-0.88, p < 0.01, respectively). The 5-year CSS was 79% and 74%, in favor of preop RT (log-rank, p < 0.05). Preop RT was also significantly associated with a reduced risk for local and distant relapse compared with postop RT. CONCLUSION: Preoperative RT is associated with a reduced cancer-specific mortality compared with postoperative RT in STS. The results of this study may serve as motivation to conduct future prospective studies with larger patient numbers.

Radiotherapy and extent of surgical resection in retroperitoneal soft-tissue sarcoma: multi-institutional analysis of 261 patients.

BACKGROUND AND OBJECTIVE: To examine the impact of adjuvant radiotherapy (RT) and surgical technique on survival in retroperitoneal soft-tissue sarcoma. METHODS: A retrospective analysis was conducted using the National Oncology Database, a proprietary database of aggregated tumor registries owned by IMPAC(R) Medical Systems (Sunnyvale, CA). Patients who received definitive surgery with negative or microscopic-positive margins were included. Multivariate analysis was performed using the Cox proportional hazards model. Survival curves were estimated by the Kaplan-Meier method and were compared for statistical significance (P < 0.05) using the log-rank test. RESULTS: Two hundred sixty-one patients met inclusion criteria. The median follow-up was 59 months (range 0.2-186 months). The 5-year cause-specific survival (CSS) and local failure-free survival (LFFS) were 73% and 66%, respectively. Grade, margin status, and histology were independent predictors for CSS (P < 0.05). Adjuvant RT was associated with a significant improvement in LFFS over surgery alone (hazard ratio = 0.42, 95% confidence interval 0.21-0.86, P < 0.05). Patients receiving simple excision and RT had a 5-year LFFS of 88%, significantly higher than wide resection with or without RT (log-rank, P < 0.05). CONCLUSION: Adjuvant RT is associated with a lower risk of local relapse compared to surgery alone. The impact of surgical technique on adjuvant RT efficacy warrants further study.

Radiation-associated kidney injury.

The kidneys are the dose-limiting organs for radiotherapy to upper abdominal cancers and during total body irradiation. The incidence of radiotherapy-associated kidney injury is likely underreported owing to its long latency and because the toxicity is often attributed to more common causes of kidney injury. The pathophysiology of radiation injury is poorly understood. Its presentation can be acute and irreversible or subtle, with a gradual progressive dysfunction over years. A variety of dose and volume parameters have been associated with renal toxicity and are reviewed to provide treatment guidelines. The available predictive models are suboptimal and require validation. Mitigation of radiation nephropathy with angiotensin-converting enzyme inhibitors and other compounds has been shown in animal models and, more recently, in patients.