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Intraoperative radiotherapy; Overall survival; Progression-free survival Radioterapia intraoperatoria; Supervivencia global; Supervivencia libre de progresión Radioteràpia intraoperatòria; Supervivència global; Supervivència lliure de progressió Objective To report survival outcomes in patients with locally recurrent gynecologic cancers managed with curative-intent radical extirpation, perioperative external beam radiotherapy, and intraoperative radiotherapy (IORT). Patients and Methods We conducted a retrospective cohort analysis of 44 patients with locally recurrent gynecologic cancer treated at a single tertiary-care center (Mayo Clinic in Arizona) over a 15-year period (January 1, 2004, to July 31, 2019). This cohort included patients with uterine (n=21, 47.7%), ovarian (n=3, 6.8%), cervical (n=11, 25.0%), vaginal (n=2, 4.5%), vulvar (n=1, 2.3%), and unknown primary (n=6, 13.6%) cancer. Curative-intent radical extirpation included pelvic exenteration (n=13, 29.5%), laterally extended endopelvic resection (n=22, 50.0%), excision of para-aortic lymph node metastasis (n=8, 18.2%), and radical vaginectomy (n=1, 2.3%). Of the 44 patients in our cohort, 37 (84.1%) received IORT and 7 (15.9%) had intended to receive IORT but did not receive it. Results The median follow-up for the 44 patients was 12 months (range, 1 to 161 months). For patients who received IORT, the median progression-free survival (PFS) and overall survival (OS) were 13 and 21 months, respectively, and the 3-year cumulative incidence of central, locoregional, and distant recurrence was 27.0% (10 of 37), 40.5% (15 of 37), and 37.8% (14 of 37), respectively. Surgical margins were classified as negative (28 of 44, 63.6%), microscopic (11 of 44, 25.0%), or macroscopic (5 of 44, 11.4%). Negative, microscopic, and macroscopic surgical margins resulted in 3-year PFS of 51.8%, 20.5%, and 0%, respectively (P=.01) and 3-year OS of 62.9%, 20.0%, and 0%, respectively (P=.035). Progression-free survival (P=.69) and OS (P=.88) were not different between patients with negative surgical margins who received (n=21) and did not receive (n=7) IORT. Ten of 37 patients (27.0%) had development of grade 3 or higher toxicities, with 1 death due to sepsis. Conclusion Complete tumor resection at the time of curative-intent radical extirpation achieved higher rates of PFS and OS regardless of IORT administration.

Purpose To assess acute gastrointestinal (GI) and genitourinary (GU) toxicities of intensity-modulated proton therapy (IMPT) targeting the prostate/seminal vesicles and pelvic lymph nodes for prostate cancer. Materials and Methods A prospective study (ClinicalTrials.gov: NCT02874014), evaluating moderately hypofractionated IMPT for high-risk or unfavorable intermediate-risk prostate cancer, accrued a target sample size of 56 patients. The prostate/seminal vesicles and pelvic lymph nodes were treated simultaneously with 6750 and 4500 centigray radiobiologic equivalent (cGyRBE), respectively, in 25 daily fractions. All received androgen-deprivation therapy. Acute GI and GU toxicities were prospectively assessed from 7 GI and 9 GU categories of the Common Terminology Criteria for Adverse Events (version 4), at baseline, weekly during radiotherapy, and 3-month after radiotherapy. Fisher exact tests were used for comparisons of categorical data. Results Median age was 75 years. Median follow-up was 25 months. Fifty-five patients were available for acute toxicity assessment. Sixty-two percent and 2%, respectively, experienced acute grade 1 and 2 GI toxicity. Grade 2 GI toxicity was proctitis. Sixty-five percent and 35%, respectively, had acute grade 1 and 2 GU toxicity. The 3 most frequent grade 2 GU toxicities were urinary frequency, urgency, and obstructive symptoms. None had acute grade ≥ 3 GI or GU toxicity. The presence of baseline GI and GU symptoms was associated with a greater likelihood of experiencing acute GI and GU toxicity, respectively. Of 45 patients with baseline GU symptoms, 44% experienced acute grade 2 GU toxicity, compared with only 10% among 10 with no baseline GU symptoms (P = 0.07). Although acute grade 1 and 2 GI and GU toxicities were common during radiotherapy, most resolved at 3 months after radiotherapy. Conclusion A moderately hypofractionated IMPT targeting the prostate/seminal vesicles and regional pelvic lymph nodes was well tolerated with no acute grade ≥ 3 GI or GU toxicity. Patients with baseline GU symptoms had a higher rate of acute grade 2 GU toxicity.

Objective To analyze clinical characteristics and survival of patients with primary vaginal cancer. Methods Retrospective analysis of patients with primary squamous, adenocarcinoma and adenosquamous cell carcinoma of the vagina identified from the Mayo Clinic Cancer Registry between 1998 and 2018. Results A total of 124 patients were identified: stage I, 39 patients; stage II, 44, stage III, 20 and stage IV, 21. Patients with stage III and IV were older as compared to stage I and II. (mean ages 61 vs 67) (p = 0.024). Squamous cell carcinoma made up 71% of tumors. History of other malignancy was present in 24% patients. Median follow-up time was 60 months (range 1–240). Five-year PFS in stage I, II, III and IV was 58.7%, 59.4%, 67.3% and 31.8%, respectively (p = 0.039). Five-year DSS was 84.3%, 73.7%, 78.7% and 26.5% respectively (p 4 cm, entire vaginal involvement, and lymph node (LN) metastasis were poor prognosticators in univariate analysis. Primary surgery in stage I/II patients had similar survival outcomes as compared to primary radiation, but post-operative RT rate was 55%. Brachytherapy alone was associated with a high local recurrence (80%) in stage I/II patients. The addition of brachytherapy had improved 5-year PFS and DSS than EBRT alone in patients with stage III/IVA. (p Conclusion Surgery or radiation is effective treatment for vaginal cancer stage I and II. The addition of brachytherapy to external pelvic radiation increases survival in stages III-IV.

Symptomatic vertebral hemangiomas (SVHs) are rare benign tumors that when symptomatic require procedural intervention or radiotherapy (RT). Although conventionally-fractionated RT has been an alternative to surgical resection, there is very little data on stereotactic body radiotherapy (SBRT) for SVHs. Six consecutively treated patients with SVHs underwent definitive single-fraction SBRT from 2010 to 2018 at our institution. The RT planning parameters, treatment, outcome, and toxicities are reported for 6 patients with 6 total SVHs treated with single-fraction SBRT. Each patient presented with back pain and received single-fraction SBRT to a thoracic vertebral body hemangioma. One patient had received radiofrequency ablation prior to SBRT. The median SBRT dose was 18 Gy (range, 13–20). Following SBRT, 4 (67%) patients reported improvement in presenting symptoms and 2 patients (33%) were refractory. There were no acute or chronic toxicities associated with SBRT including esophagitis, vertebral compression fractures, or myelopathy. To date, this is the largest series of single-fraction SBRT for SVHs. Single fraction SBRT appears to be a feasible option for SVHs. Further studies are needed to confirm our preliminary findings and optimize dose fractionation.

Objective Radiation therapy (RT) is the primary treatment of intracranial metastasis (ICM) from lung cancer (LC). Radiation necrosis (RN) has been reported post-RT with an incidence of 5% to 24%. We reviewed the spectrum of imaging changes in patients treated with RT for ICM from LC in an effort to identify potential risk factors for RN. Methods We reviewed 63 patients with LC and ICM who received RT (radiosurgery [stereotactic radiosurgery] with/without whole brain radiation therapy) at our institution between 2013 and 2018. Data evaluated included demographics, tumor type, ICM burden and location, chemotherapy, surgery, and RT details as well as treatment choices and outcomes. Results Of the 63 patients, clinical and radiographic criteria for RN were noted in 24 (38%) as early as 2 months and as late as 5 years posttreatment. Six patients required surgical resection due to refractory symptoms revealing pathology-proven RN and occasionally tumor. Patients were significantly more likely to develop RN if they had surgical resection of an ICM (45.8% vs. 20.5%, P=0.05). No differences were found in location, size, or genetic profile of lesions. In total, 80% of patients received treatment for symptoms and/or radiographic change. This was generally a combination of steroids, bevacizumab, laser interstitial thermal treatment, or surgical resection. Most patients required >1 treatment modality. Conclusions This review of outcomes of RT for ICM in LC demonstrates a higher rate of RN than previously reported in the literature in those having had a surgical resection plus stereotactic radiosurgery. Our observation of RN as late as 5 years post-RT for ICM necessitates clinician awareness.

Purpose To quantitatively assess volumetric changes after hypofractionated stereotactic radiation therapy (HFSRT) in patients treated for vestibular schwannomas and meningiomas. Methods and materials We retrospectively reviewed records of patients treated with HFSRT at our institution from 2002 to 2014. Patients received a median dose of 25 Gy in 5 fractions. After treatment, they underwent clinical and radiologic follow-up with magnetic resonance imaging (MRI) at 3- to 12-month intervals. Gross tumor volume was outlined on each thin slice of contrast-enhanced T1 series before and on each scan after HFSRT. Volumetric changes were calculated and compared with neuroradiologist interpretations. Results Forty-three patients underwent 182 MRI scans. Tumor types included vestibular schwannoma (n = 34) and meningioma (n = 9). Median follow-up time was 29 months. Median gross tumor volume was 3.1 cm3. Local control was 81.4% for the entire cohort at the time of last follow-up. Transient volume expansion was noted in 17 patients (50%) with vestibular schwannoma and 2 (22%) with meningioma. For all patients, transient volume expansion and subsequent regression occurred at a median time of 5.5 and 12 months, respectively. Neuroradiologist agreement with regard to tumor regression, progression, or stability occurred in 155 of 182 total reports (85%). The largest discordance identified was a stable finding on the MRI interpretation when the measured volumetric change exceeded 20% (n = 24 [13%]). Conclusions HFSRT is associated with excellent local control and a low incidence of toxicity. With volumetric MRI measurement, transient volume expansion was a common finding and was associated with temporary adverse effects. Although the neuroradiologist’s interpretation generally agreed with the volumetric MRI measurement, the overall 15% discordance rate emphasizes the potential benefit of considering volumetric measurements, which may help clinicians correlate posttreatment symptoms with MRI findings.

Purpose/Objective(s) High linear energy transfer (LET) radiotherapy may cause unexpected adverse events (AEs) in head and neck (H&N) cancer patients treated by intensity-modulated proton therapy (IMPT). In this exploratory study, we propose to investigate the effects of LET upon AEs in IMPT using dose-linear-energy-transfer volume histograms (DLVHs) and seed spots analysis. Materials/Methods We included 14 H&N patients with unanticipated CTCAEv4.0 grade≥3 AEs for analysis. The AE regions were contoured and the corresponding DLVHs of the AE regions were generated. DLVH was constructed with physical dose (Gy) and LET (keV/µm) as independent variables. The normalized volume of the structure was contoured as iso-volume lines in the dose-LET plane. All voxels in the structure were mapped into the dose-LET plane as dots to see how the dots with similar dose and LET were clustered. For seed spot analysis, we selected voxels at the top edge of the DLVH plots as critical voxels. Individually clustered critical voxels that are geometrically apart were considered as independent seed spots. Median dose/LET from seed spots were extracted. Bivariate-linear-regression models were established for all AEs. The dose and LET product (xBD) volume constraint of osteoradionecrosis was obtained using the receiver operating characteristic curve of 4 osteoradionecrosis patients and 15 additional independent control patients. Results Dose played a dominant role for in-field AEs such as hemorrhage and ulceration, while LET played an important role in out-of-field AEs such as osteoradionecrosis and mucositis. Intercept-free linear models between the reciprocal of dose and LET were found for different AEs. The corresponding xBD threshold values were included in Table 1. The xBD volume constraint of osteoradionecrosis was derived V (xBD≥275.18 Gy•keV/μm) Conclusion Our observations suggested that dose and LET can contribute to AEs in a complicated fashion. Using the intercept-free bivariate linear regression model, we found a LET-enhancing effect for all 6 AEs included in the study, substantiated by the positive slopes of the empirical dose-LET models. The xBD volume constraint of osteoradionecrosis was derived and showed good performance. We believe that both DLVH and seed spot analysis could be powerful tools for patient outcome studies in IMPT.

Background Radium-223 ( 223 Ra) improves survival in patients with metastatic castration-resistant prostate cancer (mCRPC). This retrospective analysis was performed to better understand its efficacy in routine clinical practice and identify factors associated with survival. Materials and Methods Sixty-four patients with mCRPC who received 223 Ra between 2013 and 2015 were the basis of this retrospective study. Clinical outcomes and patient characteristics were obtained. Potential prognostic factors for survival were evaluated by univariate analysis using the log-rank test and multivariate analysis using the Cox proportional hazard method. Results The median survival was 12.9 months. Twenty-one patients (33%) developed a skeletal event, and the median time to the first skeletal event was 4.4 months. In univariate analysis, factors significantly associated with survival included: no prior chemotherapy, ≤ 5 bone metastases, baseline prostate-specific antigen (PSA) ≤ 36 ng/mL, baseline alkaline phosphatase (ALP) 12 g/dL, ALP response after 223 Ra treatment, PSA decrease during 223 Ra treatment, and absence of > 25% PSA increase during 223 Ra treatment. In multivariate analysis, 4 factors remained significant: no prior chemotherapy, ≤ 5 bone metastases, baseline ALP 223 Ra treatment. Conclusion When 223 Ra is administered in routine clinical practice, clinical outcomes can be more variable than those reported in the randomized study owing to patient heterogeneity. Four factors were identified to be significantly associated with survival after 223 Ra treatment. These pretreatment factors may be used as stratification factors in future studies to investigate whether 223 Ra would be more effective for patients with newly diagnosed metastatic disease that is sensitive to androgen deprivation therapy.

Purpose This report describes the long-term outcomes of a prospective trial of intensity modulated radiation therapy (IMRT), integrating a 111 In capromab pendetide (ProstaScint) scan-directed simultaneous integrated boost (SIB) for localized prostate cancer. Methods and Materials Seventy-one patients with T1N0M0 to T4N0M0 prostate cancer were enrolled, and their ProstaScint and pelvic computed tomography scans were coregistered for treatment planning. The entire prostate received 75.6 Gy in 42 fractions with IMRT, whereas regions of increased uptake on ProstaScint scans received 82 Gy as an SIB. Patients with intermediate- and high-risk disease also received 6 months and 12 months of adjuvant hormonal therapy, respectively. Results The study enrolled 31 low-, 30 intermediate-, and 10 high-risk patients. The median follow-up was 120 months (range, 24-150 months). The 10-year biochemical control rates were 85% for the entire cohort and 84%, 84%, and 90% for patients with low-, intermediate-, and high-risk disease, respectively. The 10-year survival rate of the entire cohort was 69%. Pretreatment prostate-specific antigen level >10 ng/mL and boost volume of >10% of the prostate volume were significantly associated with poorer biochemical control and survival. The outcomes were compared with those of a cohort of 302 patients treated similarly but without the SIB and followed up for a median of 91 months (range, 6-138 months). The 5- and 10-year biochemical control rates were 86% and 61%, respectively, in patients without the SIB compared with 94% and 85%, respectively, in patients in this trial who received the SIB ( P =.02). The cohort that received an SIB did not have increased toxicity. Conclusions The described IMRT strategy, integrating multiple imaging modalities to administer 75.6 Gy to the entire prostate with a boost dose of 82 Gy, was feasible. The addition of the SIB was associated with greater biochemical control but not toxicity. Modern imaging technology can be used to locally intensify the dose to tumors and spare normal tissues, producing very favorable long-term biochemical disease control.

BackgroundTemozolomide (TMZ) has been the standard-of-care chemotherapy for glioblastoma (GBM) patients for more than a decade. Despite this long time in use, significant questions remain regarding how best to optimize TMZ therapy for individual patients. Understanding the relationship between TMZ response and factors such as number of adjuvant TMZ cycles, patient age, patient sex, and image-based tumor features, might help predict which GBM patients would benefit most from TMZ, particularly for those whose tumors lack O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation.Methods and findingsUsing a cohort of 90 newly-diagnosed GBM patients treated according to the standard of care, we examined the relationships between several patient and tumor characteristics and volumetric and survival outcomes during adjuvant chemotherapy. Volumetric changes in MR imaging abnormalities during adjuvant therapy were used to assess TMZ response. T1Gd volumetric response is associated with younger patient age, increased number of TMZ cycles, longer time to nadir volume, and decreased tumor invasiveness. Moreover, increased adjuvant TMZ cycles corresponded with improved volumetric response only among more nodular tumors, and this volumetric response was associated with improved survival outcomes. Finally, in a subcohort of patients with known MGMT methylation status, methylated tumors were more diffusely invasive than unmethylated tumors, suggesting the improved response in nodular tumors is not driven by a preponderance of MGMT methylated tumors.ConclusionsOur finding that less diffusely invasive tumors are associated with greater volumetric response to TMZ suggests patients with these tumors may benefit from additional adjuvant TMZ cycles, even for those without MGMT methylation.

Purpose Intensity Modulated Radiation Therapy (IMRT) allows for significant dose reductions to organs at risk in prostate cancer patients. However, the accurate delivery of IMRT plans can be compromised by patient positioning errors. The purpose of this study was to determine if the modeling of grade ≥ 2 acute rectal toxicity could be used to monitor the quality of IMRT protocols. Materials and methods 79 patients treated with Image and Fiducial Markers Guided IMRT (FMIGRT) and 302 patients treated with trans-abdominal ultrasound guided IMRT (USGRT) was selected for this study. Treatment plans were available for the FMIGRT group, and hand recorded dosimetric indices were available for both groups. We modeled toxicity in the FMIGRT group using the Lyman Kutcher Burman (LKB) and Univariate Logistic Regression (ULR) models, and we modeled toxicity in USGRT group using the ULR model. We performed Receiver Operating Characteristics (ROC) analysis on all of the models and compared the Area under the ROC curve (AUC) for the FMIGRT and the USGRT groups. Results The observed Incidence of grade ≥ 2 rectal toxicity was 20% in FMIGRT patients and 54% in USGRT patients. LKB model parameters in the FMIGRT group were TD50=56.8 Gy, slope m=0.093, and exponent n=0.131. The most predictive indices in the ULR model for the FMIGRT group were D25% and V50 Gy. AUC for both models in the FMIGRT group was similar (AUC=0.67). The FMIGRT URL model predicted less than a 37% incidence of grade ≥ 2 acute rectal toxicity in the USGRT group. A fit of the ULR model to USGRT data did not yield a predictive model (AUC=0.5). Conclusion Modeling of acute rectal toxicity provided a quantitative measure of the correlation between planning dosimetry and this clinical endpoint. Our study suggests that an unusually weak correlation may indicate a persistent patient positioning error.

Purpose Despite the intra- and intertumoral heterogeneity seen in glioblastoma multiforme (GBM), there is little definitive data on the underlying cause of the differences in patient survivals. Serial imaging assessment of tumor growth allows quantification of tumor growth kinetics (TGK) measured in terms of changes in the velocity of radial expansion seen on imaging. Because a systematic study of this entire TGK phenotype—growth before treatment and during each treatment to recurrence —has never been coordinately studied in GBMs, we sought to identify whether patients cluster into discrete groups on the basis of their TGK. Patients and Methods From our multi-institutional database, we identified 48 patients who underwent maximally safe resection followed by radiotherapy with imaging follow-up through the time of recurrence. The patients were then clustered into two groups through a k-means algorithm taking as input only the TGK before and during treatment. Results There was a significant survival difference between the clusters ( P = .003). Paradoxically, patients among the long-lived cluster had significantly larger tumors at diagnosis ( P = .027) and faster growth before treatment ( P = .003) but demonstrated a better response to adjuvant chemotherapy ( P = .048). A predictive model was built to identify which cluster patients would likely fall into on the basis of information that would be available to clinicians immediately after radiotherapy (accuracy, 90.3%). Conclusion Dichotomizing the heterogeneity of GBMs into two populations—one faster growing yet more responsive with increased survival and one slower growing yet less responsive with shorter survival—suggests that many patients who receive standard-of-care treatments may get better benefit from select alternative treatments.

Temozolomide (TMZ) has been the standard-of-care chemotherapy for glioblastoma (GBM) patients for more than a decade. Despite this long time in use, significant questions remain regarding how best to optimize TMZ therapy for individual patients. Understanding the relationship between TMZ response and factors such as number of adjuvant TMZ cycles, patient age, patient sex, and image-based tumor features, might help predict which GBM patients would benefit most from TMZ, particularly for those whose tumors are not MGMT methylated. Using a cohort of 90 newly-diagnosed GBM patients treated according to the Stupp protocol, we examined the relationships between several patient and tumor characteristics and volumetric and survival outcomes during adjuvant chemotherapy. Volumetric changes in MR imaging abnormalities during adjuvant therapy were used to assess TMZ response. T1Gd volumetric response is associated with younger patient age, increased number of TMZ cycles, longer time to nadir volume, and decreased tumor invasiveness. Moreover, increased adjuvant TMZ cycles corresponded with improved volumetric response only among more nodular tumors, and this volumetric response was associated with improved survival outcomes. Finally, in a subcohort of patients with known MGMT methylation status, MGMT methylated tumors were more diffusely invasive than unmethylated tumors, suggesting that the improved response in nodular tumors is not driven by a preponderance of MGMT methylated tumors. Our finding that less diffusely invasive tumors are associated with greater volumetric response to TMZ suggests that patients with these tumors may benefit from additional cycles of adjuvant TMZ, even for those without MGMT methylation.

BACKGROUND Radiation is an integral component of the multidisciplinary treatment of patients with intracranial metastasis (ICM) from melanoma. The risk of radiation necrosis (RN) post-treatment can range from 5–25%. We retrospectively evaluated pre- and post-radiation clinical and radiographical characteristics in patients with ICM from melanoma to identify potential risk factors for RN. METHODS After IRB approval, patients with ICM from melanoma who received radiation at our institution between 2013 and 2018 were retrospectively reviewed. We recorded demographics, intracranial metastasis (burden and location), systemic therapy, resection, stereotactic radiosurgery versus whole brain radiation, and outcomes. Brain MRI was evaluated using the Response Assessment in Neuro-Oncology criteria (RANO). RESULTS A total of 27 patients were included in the study. RN was diagnosed in 14 patients (52%) at one month to three years following radiation. Cerebellar location (n=7) was significantly associated with RN (p=0.0058). Metastasis-associated hemorrhage was present in 7 patients, 6 of which developed RN (43% vs 8%, p=0.08). Surgical resection prior to radiation was performed in 9 patients, 7 of which developed RN (50% vs 15%, p=0.1). RN appeared to be less often diagnosed when ICM were treated with higher doses of radiation (24 Gy vs 20 Gy, p=0.07). Systemic treatment was administered prior to radiation in 25 patients and we found no relationship with systemic therapy type and RN. Presumed RN was treated in 12 of 14 patients (86%). Steroids or surgical resection were the primary treatment modalities, with laser ablation used in 1 case. Following treatment, improvement was noted in 3 patients radiographically and in 1 of these clinically. CONCLUSIONS This series of patients with radiotherapy-treated brain metastases from melanoma reveals cerebellar involvement, hemorrhage, and prior surgical resection as potential risk factors for radiation necrosis. Neoadjuvant systemic treatment did not appear to be a risk factor in our review.

Background: A possible association between the level of prostate specific antigen (PSA) and the use of some commonly prescribed medications has been reported in recent studies. Most of these studies were carried out in general populations of men who were screened for prostate cancer using the PSA test. We reported on the association between the initial PSA level and the use of statins, metformin and alpha-blockers in patients who were diagnosed with prostate cancer and presented for radiation therapy. Methods: Three hundred and eighty one patients treated between the years of 2000-2005 and 2009-2012 were included in this retrospective study. The information about statin, metformin and alpha-blockers use was recorded immediately prior to treatment. Differences in PSA levels prior to treatment by medication status were estimated using univariate and multivariate linear regression on log PSA values. Results: Compared with men who were not on these medications, the PSA level at presentation was 20% lower for statin users (p = 0.002) and 33% lower for metformin users (p = 0.004). We did not observe statistically significant associations between the use of statins or metformin and cancer stage, National Comprehensive Cancer Network (NCCN) risk score, or therapy outcome. A statistically significant association between the NCCN risk score and the use of alpha-blockers was observed (p = 0.002). Conclusions: We found that statins and metformin were associated with lower PSA levels in prostate cancer patients to an extent that could influence management decisions. We found no statistically significant associations between the use of these medications and treatment outcomes.

Aim: To model acute rectal toxicity in Intensity Modulated Radiation Therapy (IMRT) for prostate cancer using dosimetry and patient specific characteristics. Methods: A database of 79 prostate cancer patients treated with image guided IMRT was used to fit parameters of Lyman-Kutcher-Burman (LKB) and logistic regression Normal Tissue Complications Probability (NTCP) models to acute grade ≥ 2 rectal toxicities. We used a univariate regression model to find the dosimetric index which was most correlated with toxicity and a multivariate logistic regression model with machine learning algorithm to integrate dosimetry with patient specific characteristics. We used Receiver Operating Characteristics (ROC) analysis and the area under the ROC curve (AUC) to quantify the predictive power of models. Results: Sixteen patients (20.3%) developed acute grade≥2 rectal toxicity. Our best estimate (95% confidence interval) of LKB model parameters for acute rectal toxicity are exponent n=0.13 (0.1-0.16), slope m=0.09 (0.08–0.11), and threshold dose TD50=56.8 (53.7-59.9) Gy. The best dosimetric indices in the univariate logistic regression NTCP model were D25% and V50Gy. The best AUC of dosimetry only modeling was 0.67 (0.54, 0.8). In the multivariate logistic regression two patient specific variables were particularly strongly correlated with acute rectal toxicity, the use of statin drugs and PSA level prior to IMRT, while two additional variables, age and diabetes were weakly correlated. The AUC of the logistic regression NTCP model improved to 0.88 (0.8, 0.96) when patient specific characteristics were included. In a group of 79 patients, 40 took Statins and 39 did not. Among patients who took statins, (4/40)=10% developed acute grade ≥2 rectal toxicity, compared to (12/39)=30.8% who did not take statins (p=0.03). The average and standard deviation of PSA distribution for patients with acute rectal toxicity was 5.77 2.27 tox PSA = ± and it was 9.5 7.8 notox PSA = ± for the remainder (p=0.01). Conclusions: Patient specific characteristics strongly influence the likelihood of acute grade ≥ 2 rectal toxicity in radiation therapy for prostate cancer.

There has been significant progress made in the diagnosis and treatment of brain tumors over the past 15 years. This has largely been due to significant advances in radiographic imaging capabilities that have allowed for much earlier detection of disease, both new and recurrent. Advances in surgical and radiotherapy techniques and technology have also affected the care of these patients. More recent advances in chemotherapy options and double and triple crossover clinical trials are beginning to have an impact in the treatment of malignant brain tumors. This article will address the 4 most common brain tumors practicing physicians see and will review the current concepts in treating these tumors.

To identify prognostic factors and evaluate biochemical control rates for patients with localized prostate cancer treated with either high-dose intensity-modulated radiotherapy (IMRT) or conventional-dose three-dimensional conformal radiotherapy 3D-CRT.Four hundred sixteen patients with a minimum follow-up of 3 years (median, 5 years) were included. Two hundred seventy-one patients received 3D-CRT with a median dose of 68.4 Gy (range, 66-71 Gy). The next 145 patients received IMRT with a median dose of 75.6 Gy (range, 70.2-77.4 Gy). Biochemical control rates were calculated according to both American Society for Therapeutic Radiology and Oncology (ASTRO) consensus definitions. Prognostic factors were identified using both univariate and multivariate analyses.The 5-year biochemical control rate was 60.4% for 3D-CRT and 74.1% for IMRT (p0.0001, first ASTRO Consensus definition). Using the ASTRO Phoenix definition, the 5-year biochemical control rate was 74.4% and 84.6% with 3D-RT and IMRT, respectively (p = 0.0326). Univariate analyses determined that PSA level, T stage, Gleason score, perineural invasion, and radiation dose were predictive of biochemical control. On multivariate analysis, dose, Gleason score, and perineural invasion remained significant.On the basis of both ASTRO definitions, dose, Gleason score, and perineural invasion were predictive of biochemical control. Intensity-modulated radiotherapy allowed delivery of higher doses of radiation with very low toxicity, resulting in improved biochemical control.

Purpose: This analysis was performed to determine the long-term results of a Phase I trial that included 3-times-a-day radiotherapy (TIDRT) and concurrent daily cisplatin (CDDP) for Stage III non–small-cell lung cancer. Methods and Materials: Twenty patients with Stage III non–small-cell lung cancer were treated with TIDRT delivered over 12 weekdays that included 57.6 Gy administered in 1.5 Gy fractions at 8 a.m. and 4 p.m., and 1.8 Gy fractions at noon. AP-PA fields were used at 8 a.m. and 4 p.m. Opposed oblique off cord fields were used at noon. The first 5 patients were given no CDDP, the second 5 patients received 5 mg/m 2 of CDDP, and the remaining 10 patients received 7.5 mg/m 2 of CDDP. All survivors were followed for greater than 5 years. Results: The maximum tolerated dose of daily CDDP during this program of radiation therapy was 7.5 mg/m 2 . None of the patients died as a result of toxicity. The median survival was 19.2 months, and the 5-year survival rate was 25%. Tumor response and patterns of failure were also evaluated. Conclusions: This study was performed to determine the maximum tolerated dose of CDDP when administered daily during an aggressive program of TIDRT. The survival results were promising, suggesting that the combination of TIDRT and systemic therapy deserves further study.

Purpose A retrospective study to evaluate the outcome of salvage radiotherapy (RT) for clinically apparent, palpable prostate cancer recurrence after radical prostatectomy (RP). Methods and materials Forty-two patients underwent RT for clinically apparent recurrent prostate cancer after RP between 1993 and 1999. The end points and treatment variables of biochemical disease-free survival were evaluated statistically. Results The median follow-up was 4.3 years. All 42 patients experienced resolution of clinically detectable recurrence within 1 year after RT. The 5-year biochemical disease-free survival, local control, freedom from distant metastases, and overall survival rate was 27%, 94%, 82%, and 78%, respectively. The initial pathologic stage (T3 or T4; p = 0.04) and interval ( p = 0.01) were independent predictors of biochemical failure, and RT simulation without contrast ( p = 0.05) was nearly significant on multivariate analysis. Three patients (7%) experienced chronic Grade 3 or 4 RT-related toxicity. Conclusion Salvage prostate bed RT for clinically apparent locally recurrent prostate cancer after RP provides effective local tumor control with modest durable biochemical control. Patients irradiated with a better simulation technique were found to have a more favorable outcome. A consensus on a definition of biochemical disease-free survival after salvage RT is critical for meaningful comparison of the available data and to future progress in treating this disease process.

Purpose: In this retrospective study we determined the results of salvage external beam radiation therapy (RT) to the prostate bed for isolated increase of serum prostate specific antigen (PSA) after radical prostatectomy.Materials and Methods: A total of 60 patients underwent RT for PSA failure after radical prostatectomy from 1993 to 1999. Median followup was 51 months. Biochemical disease-free survival (bDFS) with a serum PSA of 0.3 ng/ml or less was estimated using the Kaplan-Meier method. Potential prognostic factors were evaluated for significant associations with bDFS.Results: Median PSA before RT was 0.69 ng/ml. Median radiation dose was 64.8 Gy. The 5-year actuarial bDFS was 45%. There were 32 patients with a minimum followup of 4 years (median 73 months) who experienced a 5-year bDFS rate of 43%. PSA before RT (p = 0.016), RT dose (p = 0.026), surgical margin involvement (p = 0.017) and Gleason score (p = 0.018) were identified as prognostic factors for bDFS. A significant association wi...

e16555 Background: The ProtecT trial underscores the importance of treatment in men with prostate cancer and life expectancies > 10 years and the validity of radiation therapy (RT). RT can be given with photons or protons (PT). To address the controversy of which is better, clinical outcomes of photon-based intensity modulated RT (IMRT) and PT cohorts from 2 institutions were directly compared. Methods: Under respective IRB approvals, data from 2 cohorts were analyzed. The first was 301 men treated with ultrasound image guided IMRT from 2000-05 to 75.6 Gy in 42 fractions. The second was 1214 men treated with fiducial image guided PT from 2006-10 to 78 CGE in 39 fractions. Median age and followup were 74 y and 7.2 y for IMRT and 66 y and 5.6 y for PT. Hormone therapy (ADT) was used with IMRT and PT, respectively, in 3% and 7% of low-risk patients, 25% and 9.9% of intermediate-risk, and 91% and 57.8% of high-risk. Comparative endpoints were age-stratified 5-year (5Y) survival (OS), ≥ grade 3 gastrointestinal (GI) and urologic (GU) toxicity, and 5Y freedom from biochemical progression (FFBP). Results: There was a lower prevalence of GI (1.3% vs 0.1%, p = 0.0065) and GU (4.3% vs 0.1%, p < 0.0001) toxicity at last follow-up in the PT group. In the IMRT and PT cohorts, OS rates were 90.8% and 88.7% in men ≥75 (p = 0.4083). In men < 75, OS rates were 91.6% and 97.5% in the IMRT and PT low-risk patients (p = 0.003), 92.1% and 95.5% in the IMRT and PT intermediate-risk (p = 0.0535), and 92.0% and 90.0% (p = 0.4975) in the IMRT and PT high-risk. In the IMRT and PT cohorts, respectively, FFBP rates were 92.2% and 98.9% for low-risk patients (p < 0.0001), 87.3% and 94.5% for intermediate-risk patients(p = 0.0226), and 80.3% and 74.4% for high-risk patients (p = 0.5154). Conclusions: In this retrospective comparison of outcomes in cohorts of men treated with IMRT and PT for prostate cancer, FFBP rates were better with PT for men with low- and intermediate-risk disease and similar in men with high-risk disease despite longer and more frequent use of ADT in the IMRT cohort. This study underscores the difficulty of comparing retrospective series, with differences noted in age, RT dose, and ADT use between cohorts. However, the magnitude of improvement with PT is intriguing and warrants prospective testing.

Purpose: To determine the activity and toxicity of paclitaxel and concurrent radiation for pancreatic cancer. Methods and Materials: Forty-four patients with locally unresectable pancreatic cancer were studied. Patients received paclitaxel, 50 mg/m 2 by 3 h i.v. (IV) infusion, weekly, on Days 1, 8, 15, 22 and 29. Radiation was administered concurrently to a total dose of 50.4 Gy, in 1.80 Gy fractions, for 28 treatments. Results: Nausea and vomiting were the most common toxicities, Grade 3 in five patients (12%). Two patients (5%) had Grade 4 hypersensitivity reactions to their first dose of paclitaxel. Of 42 evaluable patients, the overall response rate was 26%. The median survival was 8 months, and the 1-year survival was 30%. Conclusion: Concurrent paclitaxel and radiation demonstrate local-regional activity in pancreatic cancer. Future investigations combining paclitaxel with other local-regional and systemic treatments are warranted.

BACKGROUND. The current study was conducted to review the authors' experience in treating consecutive patients with American Joint Committee on Cancer (1997 revision) Stage III nonsmall cell lung carcinoma with aggressive preoperative chemoradiation followed by surgical resection. METHODS. The records of all patients who received preoperative chemoradiation were evaluated. Patients received 2 cycles of concurrent cisplatin and etoposide with 5940 centigrays of radiation therapy. They then were reevaluated to determine whether they were surgical candidates. If so, resection of the primary tumor with mediastinal lymph node dissection was performed 4-6 weeks after the completion of preoperative treatment. After adequate healing, an additional four cycles of cisplatin/etoposide or carboplatin/paclitaxel was given. RESULTS. Forty-two patients received preoperative chemoradiation, 33 of whom underwent surgical resection (79%), including 9 patients who underwent pneumonectomies. Complete pathologic responses were observed in 27% of these patients. Postoperative complications were noted in 21% of the patients and included persistent air leak, supraventricular arrhythmia, and empyema. There were no reported treatment-related deaths. The median follow-up was 26 months. The overall 5-year survival rate for all patients was 36.5% and was 45.3% for patients who underwent resection. A trend toward increased 5-year survival was observed in patients who had a complete pathologic response (57.1%). Univariate analysis revealed the N stage classification to be significant for predicting a complete response. Patterns of failure revealed the brain to be the most common site of first recurrence (50%) and the only site of recurrence in 36% of patients. There was only one case of local failure. CONCLUSIONS. Preoperative chemoradiation using high radiation doses is feasible with acceptable toxicity. The results of the current study suggest an increased complete pathologic response rate and increased overall survival rate compared with reports in the published literature.

Transperineal permanent brachytherapy using iodine-125 or palladium-103 seeds is a standard treatment modality for localized prostate cancer. Migration of seeds to the lungs is a common phenomenon, whereas migration of seeds to the right ventricle is a rare event. We report a case of iodine-125 seed migration to the right ventricle as demonstrated by chest CT scan and add to the very few published reports on this finding. These rare patients did not suffer adverse effects from such event.

A prospective study was performed for patients with early-stage breast cancer in which a single fraction of intraoperative electron irradiation (IOERT) was given to the tumor bed, followed by conventional fractionated whole-breast irradiation (WBRT). Patients with T1/T2N0 breast cancer underwent lumpectomy and sentinel lymph node biopsy. A tumor bed boost of 10 Gy of IOERT using 6-12 MeV electrons was administered by a dedicated mobile linear accelerator in the operating room. After adequate wound healing, 48 Gy WBRT was given to the whole breast in 24 fractions. Fifty-two patients were enrolled between February 2003 and January 2005. At a median follow-up of 79 months, there were two local relapses. The 6-year actuarial overall survival and distant control rates were 89% and 96%, respectively. At last follow-up, cosmesis was graded as excellent or good in 45 (87%), fair in five (10%), and poor in two patients (4%), respectively. Difficulty in wound healing occurred in two patients who had additional surgery later. One patient developed significant fibrosis after aspiration of a symptomatic seroma. The result of this pilot study shows the feasibility of using IOERT as the tumor bed boost in lieu of 6-8 days of standard electron beam treatment with good local control and cosmetic results. However, late surgical intervention of the lumpectomy bed may result in more pronounced tissue fibrosis and wound healing difficulty.

We evaluate long-term disease control and chronic toxicities observed in patients treated with intensity modulated radiation therapy for clinically localized prostate cancer.A total of 302 patients with localized prostate cancer treated with image guided intensity modulated radiation therapy between July 2000 and May 2005 were retrospectively analyzed. Risk groups (low, intermediate and high) were designated based on National Comprehensive Cancer Network guidelines. Biochemical control was based on the American Society for Therapeutic Radiology and Oncology (Phoenix) consensus definition. Chronic toxicity was measured at peak symptoms and at last visit. Toxicity was scored based on Common Terminology Criteria for Adverse Events v4.The median radiation dose delivered was 75.6 Gy (range 70.2 to 77.4) and 35.4% of patients received androgen deprivation therapy. Patients were followed until death or from 6 to 138 months (median 91) for those alive at last evaluation. Local and distant recurrence rates were 5% and 8.6%, respectively. At 9 years biochemical control rates were 77.4% for low risk, 69.6% for intermediate risk and 53.3% for high risk cases (log rank p = 0.05). On multivariate analysis T stage and prostate specific antigen group were prognostic for biochemical control. At last followup only 0% and 0.7% of patients had persistent grade 3 or greater gastrointestinal and genitourinary toxicity, respectively. High risk group was associated with higher distant metastasis rate (p = 0.02) and death from prostate cancer (p = 0.0012).This study represents one of the longest experiences with intensity modulated radiation therapy for prostate cancer. With a median followup of 91 months, intensity modulated radiation therapy resulted in durable biochemical control rates with low chronic toxicity.

Purpose To evaluate, in a prospective study, the use of 111 In–capromab pendetide (ProstaScint) scan to guide the delivery of a concomitant boost to intraprostatic region showing increased uptake while treating the entire gland with intensity-modulated radiotherapy for localized prostate cancer. Methods and Materials From September 2002 to November 2005, 71 patients were enrolled. Planning pelvic CT and 111 In–capromab pendetide scan images were coregistered. The entire prostate gland received 75.6 Gy/42 fractions, whereas areas of increased uptake in 111 In–capromab pendetide scan received 82 Gy. For patients with T3/T4 disease, or Gleason score ≥8, or prostate-specific antigen level >20 ng/mL, 12 months of adjuvant androgen deprivation therapy was given. In January 2005 the protocol was modified to give 6 months of androgen deprivation therapy to patients with a prostate-specific antigen level of 10–20 ng/mL or Gleason 7 disease. Results Thirty-one patients had low-risk, 30 had intermediate-risk, and 10 had high-risk disease. With a median follow-up of 66 months, the 5-year biochemical control rates were 94% for the entire cohort and 97%, 93%, and 90% for low-, intermediate-, and high-risk groups, respectively. Maximum acute and late urinary toxicities were Grade 2 for 38 patients (54%) and 28 patients (39%) and Grade 3 for 1 and 3 patients (4%), respectively. One patient had Grade 4 hematuria. Maximum acute and late gastrointestinal toxicities were Grade 2 for 32 patients (45%) and 15 patients (21%), respectively. Most of the side effects improved with longer follow-up. Conclusion Concomitant boost to areas showing increased uptake in 111 In–capromab pendetide scan to 82 Gy using intensity-modulated radiotherapy while the entire prostate received 75.6 Gy was feasible and tolerable, with 94% biochemical control rate at 5 years.

BACKGROUND: In the current study, the effects of dose escalation for localized prostate cancer treatment with intensity-modulated radiotherapy (IMRT) or permanent transperineal brachytherapy (BRT) in comparison with conventional dose 3-dimensional conformal radiotherapy (3D-CRT) were evaluated. METHODS: This study included 853 patients; 270 received conventional dose 3D-CRT, 314 received high-dose IMRT, 225 received BRT, and 44 received external beam radiotherapy (EBRT) + BRT boost. The median radiation doses were 68.4 grays (Gy) for 3D-CRT and 75.6 Gy for IMRT. BRT patients received a prescribed dose of 144 Gy with iodine-125 (I-125) or 120 Gy with palladium-103 (Pd-103), respectively. Patients treated with EBRT + BRT received 45 Gy of EBRT plus a boost of 110 Gy with I-125 or 90 Gy with Pd-103. Risk group categories were low risk (T1-T2 disease, prostate-specific antigen level ≤10 ng/mL, and a Gleason score ≤6), intermediate risk (increase in value of 1 of the factors), and high risk (increase in value of ≥2 factors). RESULTS: With a median follow-up of 58 months, the 5-year biochemical control (bNED) rates were 74% for 3D-CRT, 87% for IMRT, 94% for BRT, and 94% for EBRT + BRT (P

Purpose We report three cases of seed embolization to the right renal artery after iodine-125 (I-125) transperineal interstitial permanent prostate brachytherapy. Methods and materials Case 1: A 65-year-old man presented with right flank and back pain less than 4 months after prostatic seed implantation. CT evaluation for renal stone showed a seed embedded in the lower aspect of the right kidney. Case 2: A 73-year-old man complained of painless hematuria 3 years after prostatic seed brachytherapy. CT and subsequent abdominal angiography showed a seed embolization to a lower branch of the right renal artery. Case 3: An 84-year-old man presented with gross hematuria 7 months after prostatic seed implantation. Excretory urogram and subsequent CT demonstrated the right lower renal seed migration. Results Prostatic seed embolization to the right renal artery may cause pain and hematuria. This pattern of seed migration may be easily overlooked by imagers because it mimics renal lithiasis on cross-sectional imaging. Knowledge of prior history of permanent interstitial prostate brachytherapy and careful radiologic interpretation may help to achieve the correct diagnosis of rare renal seed migration. Conclusions We present an additional atypical site of brachytherapy seed relocation in the right renal artery in 3 patients. This type of migration is probably secondary to pulmonary arteriovenous malformation or right-to-left cardiac shunts. Awareness of the propensity of seeds to dislodge and vigilance in imaging interpretation of prostatic brachytherapy recipients are necessary for the correct diagnosis of seed embolization.

A retrospective review of the treatment of 15 breast cancer patients who received postoperative radiotherapy after a mastectomy and transverse rectus abdominis myocutaneous (TRAM) flap breast reconstruction was undertaken to determine the effects of postoperative irradiation on flap viability and cosmesis. Fourteen patients had pedicle TRAM flaps, and one patient had a free TRAM flap. Surgical complications, acute and chronic side effects of radiotherapy, and cosmetic outcome were evaluated. The median interval between the TRAM flap procedure and radiotherapy was 7 months. The median total radiation dose was 60 Gy. All patients underwent three-dimensional radiotherapy treatment planning to determine the optimal dose distribution. Mild erythema developed in 9 patients (60%), moderate erythema developed in 2 (13%), and severe erythema developed in 1 (7%). Dry desquamation developed in 6 patients (40%), whereas moist desquamation developed in none. At median follow-up of 26.4 months, only 2 (13%) of the 15 patients had fat necrosis within the TRAM flap that was not present before radiotherapy. Fourteen patients (93%) retained their flap, and 13 patients (87%) rated their cosmetic outcome as "good" to "excellent." We conclude that TRAM flaps can be irradiated with few complications and acceptable cosmetic results.

Objectives To compare, in a retrospective analysis, the outcome of salvage external beam radiotherapy (EBRT) for isolated prostate-specific antigen (PSA) elevation or palpable local recurrence after radical prostatectomy (RP). Methods We evaluated 102 men who underwent EBRT from 1993 to 1999, 60 for a rising PSA level alone and 42 for palpable local disease after RP. Biochemical disease-free survival and overall survival were calculated. Prognostic factors were evaluated to determine associations with biochemical disease-free survival. Results The 5-year rate of biochemical disease-free survival, local control, freedom from distant metastasis, and overall survival for all 102 patients was 38%, 94%, 87%, and 88%, respectively. All palpable disease resolved completely after salvage EBRT. The greatest 5-year rate of biochemical control (69%) was obtained in patients with a pre-EBRT PSA level of 0.5 ng/mL or less. The 5-year overall survival rate was significantly better for those who underwent salvage EBRT for a rising PSA level than for those with palpable recurrence (96% versus 78%, P = 0.02). A low pre-EBRT PSA level and a less than 2-year interval from RP to EBRT were independent predictors of biochemical failure. Five patients (5%) experienced chronic grade 3 or 4 RT-related toxicity. Conclusions Salvage EBRT provides excellent local control of recurrent disease after RP. Salvage EBRT before the development of palpable local disease may confer a survival benefit and decrease the risk of metastasis, and durable biochemical control was achieved best in those whose pre-EBRT PSA level was 0.5 ng/mL or less. Early referral and careful patient selection is vital for salvage EBRT to be of optimal benefit.

Purpose Urinary obstructive symptoms are the most common side effects of transperineal interstitial permanent prostate brachytherapy (TIPPB). Self-intermittent catheterization (SIC) can be used to relieve urinary retention. This study evaluated the factors associated with the probability of a patient performing SIC after TIPPB. Methods and materials We prospectively evaluated 204 patients who underwent TIPPB at Mayo Clinic Scottsdale (MCS). All patients were taught to perform SIC before implant and were instructed to do so if they could not urinate at any time after the procedure. Results Of the 204 patients, 22 patients (11%) received 103 Pd seeds and 182 patients (89%) received 125 I. Thirty-seven (18%) patients received external-beam radiotherapy (XRT) in addition to the TIPPB. SIC was performed by 69 (34%) of the 204 patients. Factors that were significantly associated with a lower frequency of SIC were prostate volumes ≤34.2 cm 3 ( p = 0.005), ≤137 seeds implanted ( p = 0.04), prostate-specific antigen (PSA) levels ≤6.35 ( p = 0.03), American Urological Association (AUA) score ≤10 ( p = 0.01), the use of 125 I ( p = 0.03), and the addition of XRT to the implant ( p = 0.02). Conclusions Significant associations were observed between the frequency of SIC and the number of seeds implanted, AUA scores, prostate volume, PSA levels, addition of XRT, and isotope used. Whereas the first four of these factors may be surrogates for prostate volume and obstructive symptoms in general, the last two factors are related to treatment decisions. These findings may aid in better patient selection and therapeutic decisions. Additionally, this information may provide a clearer understanding of the urinary side effects of TIBBP.

Few studies have evaluated the significance of the percentage of positive biopsies (PPB) and perineural invasion (PNI) for patients treated with external beam radiotherapy (EBRT) for localized prostate cancer. Our goal was to investigate the value of these factors in predicting biochemical control (bNED) after EBRT.The study cohort consisted of 331 patients who received EBRT between 1993 and 1999 for clinically localized prostate cancer. The median follow-up was 4.4 years (range, 3 months to 9.6 years). The distribution by clinical T stage was as follows: T1 in 55 (17%), T2a in 94 (28%), T2b in 76 (23%), T2c in 74 (22%), T3a in 27 (8%), and T3b in 5 (2%). The pretreatment prostate-specific antigen (iPSA) level wasor =10 ng/mL in 224 patients, 10.1-20 ng/mL in 72 patients, and20 ng/mL in 35 patients. The biopsy Gleason score wasor =6 in 216 patients andor =7 in 115 patients. On the basis of the pathology report, the PPB was calculated for 239 patients and wasor =33% in 109, 34-66% in 72, andor =67% in 58 patients. PNI was present in 30 patients. The median dose of EBRT was 68.4 Gy (range, 64-71 Gy). Patients were categorized into three risk groups: 142 patients were low risk (T1-T2, iPSAor =10 ng/mL, and Gleason scoreor =6), 137 were intermediate risk (increase in the value of one of the risk factors); and 52 patients were high risk (increase in value of two or more of the risk factors). Biochemical failure was defined as three consecutive rises in the PSA level.The 5-year bNED rate for the entire cohort was 62%. The 5-year bNED rate for the low-, intermediate, and high-risk group was 79%, 51%, and 47%, respectively (p0.0001). On univariate analysis (log-rank test), clinical stage (p = 0.0073), grade (p0.0001), iPSA (p = 0.0043), risk group (p0.0001), PPB (p = 0.0193), and presence of PNI (p = 0.0137) correlated with bNED. For T1-T2a, T2b-T2c, and T3 patients, the 5-year bNED rate was 71%, 59%, and 40%, respectively. The 5-year bNED rate was 68% for those with an iPSA level ofor =10 ng/mL and 49% for those with an iPSA level of10 ng/mL. For patients with PPBor =33%, 34-66%, andor =67%, the 5-year bNED rate was 75%, 67%, and 51%, respectively. Within the intermediate-risk group, the PPB was significantly associated with the bNED rate: 67%, 52%, and 30% for those with PPBor =33%, 34-66%, andor =67%, respectively (p = 0.0046). This association was not seen in the low- or high-risk group. The 5-year bNED rate was 64% for patients without PNI and 48% for those with PNI. On multivariate analysis (Cox proportional hazards model), the statistically significant predictive factors for bNED were risk group (p = 0.0032) and PPB (p = 0.044). Using the chi-square test, statistically significant associations between T stage, PSA level, Gleason score, and risk group with PPB were found; PNI was significantly associated with T stage and PSA level only.Our results showed that PPB and PNI have a statistically significant impact on the bNED rate in patients treated with conventional dose of EBRT (or =71 Gy). Within the intermediate-risk group, the PPB was predictive of bNED, suggesting that patients withor =33% PPB had a statistically significant better treatment outcome compared with those with a greater PPB. PNI was not significant for bNED in multivariate analysis. The effects of these two prognostic factors in patients who have been treated with higher doses of RT (or =75.6 Gy) should be studied.

This study was performed to examine potential field arrangements for irradiating non-small cell lung cancer (NSCLC) on a dose escalation study. An example patient was chosen and 7 coplanar treatment plans were created to treat a NSCLC. Two plans included prophylactic nodal irradiation (PNRT) and 5 did not. Four plans used 4 fields, 2 plans used 5 fields, and 1 plan included dynamic conformal 360 degrees rotational therapy. All plans delivered 80 Gy to the isocenter with 10-MV x-rays. Each plan was initially created without dose inhomogeneity corrections and then was recalculated with these corrections, maintaining the same weighting and number of monitor units. Avoiding PNRT spared a considerable volume of normal tissue from radiation. Plans with 5 fields generally spared normal tissues better than 4-field plans. There was no benefit to the dynamic conformal 360 degrees rotational plan. Inhomogeneity corrections revealed that higher doses were delivered to both the tumor and normal structures. Seven beam arrangements for the treatment of NSCLC were compared to develop potential beam arrangements that would be applicable to treating NSCLC on a multi-institutional dose escalation study. We favor the use of at least 5 beams in most situations. It is possible that the use of more fields would further improve plans up to a point of diminishing returns, as exemplified by the lack of benefit seen with the dynamic conformal 360 degrees rotational plan. It is possible that the use of noncoplanar fields or intensity-modulated radiation therapy (IMRT) may further improve the therapeutic ratio.

Protons interact with human tissue differently than do photons and these differences can be exploited in an attempt to improve the care of lung cancer patients. This review examines proton beam therapy (PBT) as a component of a combined modality program for locally advanced lung cancers. It was specifically written for the non-radiation oncologist who desires greater understanding of this newer treatment modality. This review describes and compares photon (X-ray) radiotherapy (XRT) to PBT. The physical differences of these beams are described and the clinical literature is reviewed. Protons can be used to create treatment plans delivering significantly lower doses of radiation to the adjacent organs at risk (lungs, esophagus, and bone marrow) than photons. Clinically, PBT combined with chemotherapy has resulted in low rates of toxicity compared to XRT. Early results suggest a possible improvement in survival. The clinical results of proton therapy in lung cancer patients reveal relatively low rates of toxicity and possible survival benefits. One randomized study is being performed and another is planned to clarify the clinical differences in patient outcome for PBT compared to XRT. Along with the development of better systemic therapy, newer forms of radiotherapy such as PBT should positively impact the care of lung cancer patients. This review provides the reader with the current status of this new technology in treating locally advanced lung cancer.

To design a decision tree according to time from irradiation and site, morphology, and number of microcalcifications for the rational treatment of patients with microcalcifications at the lumpectomy site after breast-conserving therapy (BCT), to minimize performance of biopsy.From a database of 504 women selected to receive BCT, those developing probably benign microcalcifications within 3 years of BCT received close follow-up with mammography. Patients developing fewer than four probably benign microcalcifications more than 3 years after treatment were offered mammography or biopsy. If microcalcifications appeared malignant or patients developed four or more microcalcifications after 3 years, biopsy was performed.Twenty-eight patients (29 breasts [5.7%]) developed microcalcifications confined to the lumpectomy site. Fifteen patients (15 breasts) developed microcalcifications within 3 years of BCT and were followed up with mammography. Thirteen patients (14 breasts) developed microcalcifications confined to the lumpectomy site after more than 3 years. Among the latter group, microcalcifications appeared malignant in four breasts, and biopsy specimens revealed three recurrences. The remaining 10 breasts were followed up with mammography. No patient undergoing mammographic follow-up without biopsy has had clinical evidence of local failure throughout the follow-up period.Follow-up mammography is an option when benign-appearing microcalcifications develop at the lumpectomy site depending on time of appearance and number; it is the primary recommendation when these microcalcifications develop within 3 years after treatment.

6108 Background: This pilot study evaluated whether providing clinicians with patient(pt) QOL results and symptom management pathways linked to QOL domains at the time of clinical appointment would result in improvement in QOL and treatment (tx) satisfaction. The objective was to obtain preliminary effect size estimates and logistical evidence for design of a larger, definitive trial. Methods: Oncology pts receiving 5-7 weeks of radiotherapy (RT) electronically completed QOL assessments (LASA) at baseline and biweekly prior to seeing clinicians. Was It Worth It (WIWI) and Interpersonal Patient-Provider Relationship (IPPRS) were measured at tx end. Pt endpoints (pro-rated primary endpoint LASA area under the curve (AUC), LASA changes from baseline, and WIWI responses) and clinician endpoints (IPPRS) were compared between the control group (Phase 1: no QOL feedback) and the intervention group (Phase 2: QOL feedback) via Wilcoxon, Chi-square and Fisher Exact tests. There was 80% power to detect a 10 point difference in average AUC. Results: 148 pts enrolled (79 Phase 1, 69 Phase 2) from 11/28/2008 to 09/20/2011 (sites GI (27%), Lung (22%) and Head and Neck (52%)). 68% received RT and chemo. There were consistently moderate effect sizes observed but no statistically significant differences in any AUC nor end of tx change from baseline scores. 20% fewer pts in phase 2 reported clinical deficits in overall QOL (pain). In pts receiving 7 weeks of RT, end of tx average overall QOL, mental well-being (WB), physical WB and pain severity were significantly better in Phase 2 pts. WIWI results showed 76% found participation worthwhile, 95% would participate again, and 92% would recommend the study to others. No differences between groups were found in communication between clinicians and pts (IPPRS). Conclusions: Preliminary estimates indicate potentially clinically significant improvements of moderate effect size in mental and physical WB and pain severity when clinicians received QOL real time with symptom management pathways. Further study is warranted in larger trial setting.