Search

Objectives: Invasive papillary breast cancer (IPBCA) represents 0.5% of invasive BCA, and is thought to carry a favorable prognosis. This population-based study reports on prognostic factors, treatment, and outcomes of early-stage IPBCA to explore whether there is any evidence to support less aggressive treatment., Materials and Methods: IPBCA cases from 1990 to 2009 of the recent Surveillance, Epidemiology, and End Results were analyzed. Inclusion criteria included patients with stage T1-2, N0 IPBCA. Univariate and multivariate analyses were performed using the variables of treatment, stage, race, hormone receptor status, grade (G1-3), and age. Treatment modalities included lumpectomy alone (LA), lumpectomy with radiation treatment (LRT), and mastectomy alone (MA)., Results: Among 10,485 patients, median follow-up was 56 months. Five and 10-year overall survival (OS) were 93.1% and 76.8%, respectively. Patients treated with LRT had superior mean OS 16.8 versus 14.9 years for MA (P=0.0004) and 14.2 years for LA (P=0.0003). Improved OS also correlated with lower histologic grade (P<0.0001), lower T-stage (P<0.0001), and younger age (P<0.0001). Black patients had the worst OS (12.7 y, P<0.0001)., Conclusions: LRT is associated with superior OS for early-stage invasive papillary BCA patients, when compared with LA or MA in this population-based study. The findings support the standard of care breast conservation approach for patients with invasive papillary BCA. Other prognostic factors associated with worse OS include increased age, higher T-stage, higher histologic grade, and black race.

Objectives: The objectives of this study are to explore the potential benefits of combining AdGlipr1 (or AdGLIPR1) gene therapy with radiotherapy using subcutaneous prostate and bladder cancer models., Materials and Methods: Combination adenoviral vector-mediated gene therapy and radiotherapy were applied to 178-2 BMA and TSU-Pr1 cells in vitro and colony formation and apoptosis were analyzed. In addition, combination therapies were administered to mice bearing subcutaneous 178-2 BMA and TSU-Pr1 tumors, and tumor growth suppression and survival extension were compared with the monotherapies (AdGlipr1/AdGLIPR1 and radiotherapy) or control vector Adv/CMV/βgal, as well as single-cycle treatment with 2-cycle treatment., Results: Combination treatment significantly suppressed colony formation and increased apoptosis in vitro. In vivo, combination therapy produced significant 178-2 BMA and TSU-Pr1 tumor growth suppression and survival extension compared with the monotherapies or the control. Further tumor growth suppression and survival extension were observed after 2 cycles of the combination treatment., Conclusions: Combining AdGlipr1 (AdGLIPR1) with radiotherapy may achieve additive or synergistic tumor control in selected prostate and bladder tumors, and additional therapeutic effects may result with repeated treatment cycles., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Significant developments in radiation oncology have taken place in recent years as a result of advances in radiation physics and molecular radiobiology. From the conventional 2-dimensional (2D) radiotherapy to 3-dimensional (3D) conformal radiotherapy, we have now entered the era of intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT). IMRT/IGRT allows conformal treatment of tumor and conformal avoidance of normal tissues leading to possible improvement of tumor control and decrease in treatment-related toxicity. Frameless stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT) have now become a reality, offering more treatment options in radiation oncology. With technological advances in image guidance, brachytherapy especially in early stage prostate cancer has progressed and shown excellent long-term outcome data. Charged particle therapy including proton therapy is a promising area for new development. Combining radiotherapy with the more traditional chemotherapy and hormonal therapy to novel targeted therapy and gene therapy is aimed to overcome radio-resistance, improve the radio-therapeutic index and provide better loco-regional and systemic control of cancer. A recent randomized trial in head and neck cancer has shown improved survival data when comparing combined radiotherapy and targeted therapy with radiotherapy alone. Recent advances in functional or molecular imaging offer new opportunity to improve targeting of tumor, for example, hypoxic region, and possibly to perform radiation dose painting with IMRT. Integrating PET/CT in radiotherapy has shown promise in assisting target delineation during treatment planning and assessing radiation treatment response. Cancer stem cell, gene expression profiling and nanotechnology with the implications on radio-resistance are new exciting areas requiring more research in future as we move toward personalized medicine.

Objective: Women with cervical cancer (CC) found to have positive surgical margins, positive lymph nodes, and/or parametrial invasion receive a survival benefit from postoperative chemoradiotherapy (CRT) vs. radiation therapy (RT) alone. However, older women may not benefit to the same extent, as they are at increased risk of death from non-oncologic causes as well as toxicities from oncologic treatments. This study sought to evaluate whether there was a survival benefit of CRT over RT in elderly patients with cervical cancer. Methods: The National Cancer Database was queried for patients ≥70 years old with newly diagnosed IA2, IB, or IIA CC and positive margins, parametrial invasion, and/or positive nodes on surgical resection. Statistics included logistic regression, Kaplan-Meier overall survival (OS), and Cox proportional hazards modeling analyses. Results: Altogether, 166 patients met inclusion criteria; 62 (37%) underwent postoperative RT and 104 (63%) underwent postoperative CRT. Younger patients and those living in areas of higher income were less likely to receive CRT, while parametrial invasion and nodal involvement were associated with an increased likelihood (p<0.05 for all). There were no OS differences by treatment type. Subgroup analysis by number of risk factors, as well as each of the 3 risk factors separately, also did not reveal any OS differences between cohorts. Conclusion: In the largest such study to date, older women with postoperative risk factor(s) receiving RT alone experienced similar survival as those undergoing CRT. Although causation is not implied, careful patient selection is paramount to balance treatment-related toxicity risks with theoretical outcome benefits. [ABSTRACT FROM AUTHOR]

Purpose Multiple studies have evaluated the omission of radiation therapy (RT) in elderly women with invasive carcinoma; no studies to date have assessed this question for metaplastic breast cancer (MBC). This study is the only known study describing national practice patterns and addressing the impact of RT versus observation on survival in elderly women with T1-2N0 MBC. Methods The National Cancer Data Base was queried (2004–2013) for women aged ≥70 years with T1-T2N0 MBC that underwent lumpectomy. Multivariable logistic regression ascertained factors associated with RT administration. Kaplan-Meier analysis evaluated overall survival (OS) between patients treated with or without postoperative RT. Cox proportional hazards modeling determined variables associated with OS. Propensity matching was performed in order to address indication bias. Results Of 547 total patients, 176 (32%) underwent observation, and 371 (68%) received postoperative RT. Temporal trends revealed that withholding RT steadily declined over the studied time period. RT delivery was less likely in patients not undergoing hormonal therapy or those ≥80 years old. In both the overall population and following propensity matching, delivery of RT was associated with higher OS (p < 0.001 for both). On Cox multivariate analysis, poorer OS was independently associated with advancing age, higher T stage, high-grade disease, and omitting postoperative RT (p < 0.05 for all). Conclusions Although level I evidence exists to omit RT in select elderly women, this is the only study evaluating this notion for MBC. These results do not support the routine withholding of RT in T1-2N0 MBC owing to the independent association with worse survival. [ABSTRACT FROM AUTHOR]

Background Radiation therapy (RT) utilization for elderly women with respect to human epidermal growth factor receptor 2 (HER2) receptor status has not been evaluated. Our purpose was to determine differences in RT utilization and breast cancer specific survival (BCSS) for elderly breast cancer patients with distinct molecular biomarkers. Methods The Surveillance, Epidemiology, and End Results database was queried for women ≥70 years of age diagnosed with T1N0M0 breast cancer between 2010 and 2013 receiving breast conservation. Chi-squared analysis was performed to determine the difference in RT utilization between groups. Multivariable logistic regression analysis was performed to determine predictors for RT use. Kaplan-Meier curves were created and the log-rank test done to compare differences in breast cancer specific survival (BCSS) between groups. Results A total of 12,312 patients met the inclusion criteria. Receipt of RT for patients with distinct tumor biomarkers was as follows: 55.7% for patients with Estrogen Receptor (ER) +/HER2+; 57.1% for patients with ER+/HER2-; 65.6% for patients with ER-/HER2+; and 69.2% for ER-/HER2- patients (p < 0.001). Factors associated with RT use included ER-/HER2- status, 70–74 years of age, and high grade disease, while adjuvant RT was associated with improve BCSS in ER+/HER2- and ER-/HER2- patients. Conclusions Patients 70–74 years old and those with ER-/HER2- are more likely to receive adjuvant RT. Moreover, adjuvant RT is associated with improvements in BCSS in ER+/HER2- and ER-/HER2- patients. Given possible poor compliance with hormonal therapy, the omission of RT in ER + patients, without consideration of HER2 status, should be undertaken with care. [ABSTRACT FROM AUTHOR]

Purpose: Accelerated partial breast irradiation (APBI) is an accepted treatment option in breast-conserving therapy for early stage breast cancer. However, data regarding outcomes of patients treated with multi-lumen catheter systems who have existing breast implants is limited. The purpose of this study was to report treatment parameters, outcomes, and possible dosimetric correlation with cosmetic outcome for this population of patients at our institution. Material and methods: We report the treatment and outcome of seven consecutive patients with existing breast implants and early stage breast cancer who were treated between 2009 and 2013 using APBI following lumpectomy. All patients were treated twice per day for five days to a total dose of 34 Gy using a high-dose-rate 192Ir source. Cosmetic outcomes were evaluated using the Harvard breast cosmesis scale, and late toxicities were reported using the Radiation Therapy Oncology Group (RTOG) late radiation morbidity schema. Results: After a mean follow-up of 32 months, all patients have remained cancer free. Six out of seven patients had an excellent or good cosmetic outcome. There were no grade 3 or 4 late toxicities. The average total breast implant volume was 279.3 cc, received an average mean dose of 12.1 Gy, and a maximum dose of 234.1 Gy. The average percentage of breast implant volume receiving 50%, 75%, 100%, 150%, and 200% of the prescribed dose was 15.6%, 7.03%, 4.6%, 1.58%, and 0.46%, respectively. Absolute volume of breast implants receiving more than 50% of prescribed dose correlated with worse cosmetic outcomes. Conclusions: Accelerated partial breast irradiation using a multi-lumen applicator in patients with existing breast implants can safely be performed with promising early clinical results. The presence of the implant did not compromise the ability to achieve dosimetric criteria; however, dose to the implant and the irradiated implant volume may be related with worse cosmetic outcomes. [ABSTRACT FROM AUTHOR]

Background: Studies report the need for improved pain management in the radiation oncology setting. Many patients with well controlled background pain experience breakthrough pain in cancer (BTPc) that can interrupt their treatment schedule with a potentially negative impact on outcomes. BTPc can be unpredictable and predictable; both types of pain can be managed with fast-acting analgesics, but predictable pain lends itself to anticipatory management. Methods: Five consecutive cases are described in which fentanyl pectin nasal spray (FPNS) was used to manage BTPc, with an emphasis on the anticipatory management of predictable pain in cancer patients receiving radiotherapy. Results: Patients (four men, one woman), age range 32-84 years, were diagnosed with various cancers. All patients were receiving opioid treatment for chronic pain, and experienced predictable pain with radiotherapy which included pain associated with lying on a treatment table for a sustained time during an average of 29 radiotherapy treatments; pain associated with radiation simulation and radiotherapy; pain associated with odynophagia related to increasing mucositis during treatment, resulting in decreased nutritional intake; pain associated with the customized immobilization mask for head and neck cancer patients; and pain associated with defecation. Some patients also reported pain awakening them randomly at night (eg, sleep interruption). All patients attained lower pain intensity scores (2/10 to 3/10), reduced from approximately 7/10, when they were treated with FPNS 20 minutes before a predictable pain event. No patient experienced any pain-related interruptions to their course of radiotherapy. The average number of radiotherapy sessions was 29 per patient, excluding one short-course treatment for one patient. Conclusion: FPNS offers a good solution to the management of BTPc because its fast onset of action makes it very suitable for the anticipatory treatment of predictable pain, which is likely to minimize interruptions to the radiotherapy schedule. [ABSTRACT FROM AUTHOR]

BACKGROUND: The current study was conducted to determine whether the use of cochlear-sparing intensity-modulated radiotherapy (IMRT) boost results in excess local failures in children with medulloblastoma. METHODS: Fifty children with a median age of 7.8 years underwent resection, craniospinal irradiation (CSI), IMRT posterior fossa (PF) and/or tumor bed (TB) boost, and cisplatin-based chemotherapy for medulloblastoma. For standard-risk patients, the CSI dose was 18 to 23.4 grays (Gy) and was followed either by an IMRT PF boost to 36 Gy and a TB boost of 54 to 55.8 Gy (n = 29) or by an IMRT TB boost to 55.8 Gy (n = 4). For high-risk patients, the CSI dose was 36 to 39.6 Gy followed by an IMRT PF boost to 54 to 55.8 Gy (n = 8), an IMRT PF boost to 45 Gy and a TB boost to 55.8 Gy (n = 2), or an IMRT TB boost to 55.8 Gy (n = 7). For the TB boost, a 2-cm margin around the surgical bed was treated in most patients. RESULTS: The 5-year overall and progression-free survival rates (±standard deviation) were 72% ± 6.6% and 68.3% ± 6.8%, respectively, for all patients; 77.8% ± 7.4% and 75.1% ± 7.6%, respectively, for standard-risk patients; and 60.8% ± 12.8% and 55.4% ± 12.8%, respectively, for high-risk patients. The 5-year PF control rate was 90.5% ± 4.6%. TB failures occurred in 3 patients (including 2 patients who had distant failure), whereas an isolated non-TB PF failure occurred in 1 patient. CONCLUSIONS: The use of IMRT was associated with excellent local control and did not result in excess PF failures outside of the TB. [ABSTRACT FROM AUTHOR]

Background: Perifosine is a membrane-targeted alkylphospholipid developed to inhibit the PI3K/Akt pathway and has been suggested as a favorable candidate for combined use with radiotherapy. In this study, we investigated the effect of the combined treatment of perifosine and radiation (CTPR) on prostate cancer cells in vitro and on prostate cancer xenografts in vivo.Methods: Human prostate cancer cell line, CWR22RV1, was treated with perifosine, radiation, or CTPR. Clonogenic survival assays, sulforhodamine B cytotoxity assays and cell density assays were used to assess the effectiveness of each therapy in vitro. Measurements of apoptosis, cell cycle analysis by flow cytometry and Western blots were used to evaluate mechanisms of action in vitro. Tumor growth delay assays were used to evaluate radiation induced tumor responses in vivo.Results: In vitro, CTPR had greater inhibitory effects on prostate cancer cell viability and clonogenic survival than either perifosine or radiation treatment alone. A marked increase in prostate cancer cell apoptosis was noted in CTPR. Phosphorylation of AKT-T308 AKT and S473 were decreased when using perifosine treatment or CTPR. Cleaved caspase 3 was significantly increased in the CTPR group. In vivo, CTPR had greater inhibitory effects on the growth of xenografts when compared with perifosine or radiation treatment alone groups.Conclusions: Perifosine enhances prostate cancer radiosensitivity in vitro and in vivo. These data provide strong support for further development of this combination therapy in clinical studies. [ABSTRACT FROM AUTHOR]

Purpose: We reviewed 13 years of experience with artificial urinary sphincter implantation (narrow backed cuff) at a single institution. Materials and Methods: Between 1992 and 2005, 270 patients underwent artificial urinary sphincter implantation, as performed by a single surgeon at Baylor College of Medicine, and followup data were available on 218 of them. Mean followup was 36.5 months (maximum 151.4). Of the 218 patients 60 underwent prostatectomy and pelvic radiation, 116 underwent prostatectomy without radiotherapy, 11 had neurogenic bladder and 31 underwent secondary artificial urinary sphincter implantation. Results: The complication rate did not differ among the 4 treatment groups. Complication rates were infection in 5.5% of cases, erosion in 6.0%, urethral atrophy in 9.6%, mechanical failure in 6.0% and surgical removal or revision in 27.1%. Median time to complications was 3.7 months for infection, 19.8 months for erosion, 29.6 months for atrophy, 68.1 months for failure and 14.4 months for surgery. At 5 years 75% of patients were free from revision or removal. A history of failed injectable or male sling, or of Valsalva voiding did not adversely impact the outcome. The rate of bladder neck contracture was high in artificial urinary sphincter candidates, especially in irradiated patients (36% and 57%, respectively). Patients with prior pelvic radiation continued to be at higher risk for contracture recurrence after artificial urinary sphincter implantation (12%). Two-stage UroLume® stent and artificial urinary sphincter placement offered long-term contracture and continence control in 8 of 11 patients with recurrent anastomotic contractures. Conclusions: An artificial urinary sphincter is durable treatment for sphincter deficiency even in patients with a history of complications, neurogenic bladder, pelvic radiation, bladder neck contracture, Valsalva voiding, or failed injectables or slings. [Copyright &y& Elsevier]

Purpose: The benefit of adjuvant radiotherapy after prostatectomy for patients with pathological risk factors but with an undetectable postoperative PSA remains controversial. In this retrospective study we define the benefits of elective postoperative radiotherapy in this setting. Materials and Methods: A total of 44 patients received elective postoperative radiotherapy at a single institution in the PSA era (1989 to 1995) for positive surgical margins and undetectable postoperative PSA. Radiotherapy was delivered to a median dose of 60 Gy. Clinical target volume included the prostate bed. Pelvic nodes were not treated. The four-field box technique with customized blocking of bladder, rectum and small bowels was used and defined the planning target volume. The patients were then compared to a contemporaneous group of 189 patients with positive surgical margins who underwent radical prostatectomy without any adjuvant therapy. Failure was defined as biochemical (PSA) recurrence and was timed from first detectable PSA. Results: The 5 and 10-year biochemical no evidence of disease was 90.9% and 90.9% for the elective postoperative radiotherapy group, and 66.4% and 54.5% for the observation group, respectively (p = 0.0012). Median time to biochemical failure was also longer in the elective postoperative radiotherapy group (88.6 months) compared to the observation group (43.5 months) (p <0.001). Risk factors for biochemical recurrence on multivariate analysis were Gleason score greater than 7 (p = 0.017), established extracapsular extension (p = 0.002) and lack of elective postoperative radiation (p = 0.001). Conclusions: This is one of the longest followup studies showing that elective postoperative radiation therapy is associated with improved bNED and prolonged time to recurrence. Combined radical prostatectomy and elective postoperative radiotherapy should be considered in the management of high risk prostate cancer, especially in the presence of positive surgical margins despite undetectable PSA. [Copyright &y& Elsevier]

Intensity modulated radiation therapy (IMRT) is gaining widespread use in the radiation therapy community. Prostate cancer is the ideal target for IMRT due to the growing body of literature supporting dose escalation and normal tissue limitations. The need for dose escalation and the limits of conventional radiation therapy necessitate precise patient and prostate localization as well as advanced treatment delivery. The treatment of prostate cancer has been dramatically altered by the introduction of technology that can focus on the target while avoiding normal tissue. IMRT is evolving as the treatment of the future for prostate cancer. [ABSTRACT FROM AUTHOR]

Context: Salvage radiotherapy may potentially cure patients with disease recurrence after radical prostatectomy, but previous evidence has suggested that it is ineffective in patients at the highest risk of metastatic disease progression. Objective: To delineate patients who may benefit from salvage radiotherapy for prostate cancer recurrence by identifying variables associated with a durable response. Design, Setting, and Patients: Retrospective review of a cohort of 501 patients at 5 US academic tertiary referral centers who received salvage radiotherapy between June 1987 and November 2002 for detectable and increasing prostate-specific antigen (PSA) levels after radical prostatectomy. Main Outcome Measure: Disease progression after salvage radiotherapy, defined as a serum PSA value ≥0.1 ng/mL above the postradiotherapy PSA nadir confirmed by a second PSA measurement that was higher than the first by any amount, by a continued increase in PSA level after treatment, or by the initiation of androgen deprivation therapy after treatment. Results: Over a median follow-up of 45 months, 250 patients (50%) experienced disease progression after treatment, 49 (10%) developed distant metastases, 20 (4%) died from prostate cancer, and 21 (4%) died from other or unknown causes. The 4-year progression-free probability (PFP) was 45% (95% confidence interval [CI], 40%-50%). By multivariable analysis, predictors of progression were Gleason score of 8 to 10 (hazard ratio [HR], 2.6; 95% CI, 1.7-4.1; P<.001), preradiotherapy PSA level greater than 2.0 ng/mL (HR, 2.3; 95% CI, 1.7-3.2; P<.001), negative surgical margins (HR, 1.9; 95% CI, 1.4-2.5; P<.001), PSA doubling time (PSADT) of 10 months or less (HR, 1.7; 95% CI, 1.2-2.2; P = .001), and seminal vesicle invasion (HR, 1.4; 95% CI, 1.1-1.9; P = .02). Patients with no adverse features had a 4-year PFP of 77% (95% CI, 64%-91%). When treatment was given for early recurrence (PSA level ≤2.0 ng/mL), patients with Gleas... [ABSTRACT FROM AUTHOR]

PURPOSE Tightly constricted isodose lines are generated using brachytherapy or intensity-modulated radiation therapy (IMRT) treatment planning systems for prostate cancer. Definition of margins that encompass subclinical disease extension is important to maximize dose escalation while attempting to adhere to normal tissue dose tolerances. In this study, we attempted to find predictors of extracapsular extension (ECE) and its radial distance. MATERIALS AND METHODS Pathological assessment of ECE and its radial distance was performed on 712 radical prostatectomy specimens. Preoperative data (initial prostate-specific antigen, clinical stage, ultrasound volume, and biopsy Gleason score) were evaluated for their ability to predict the presence of ECE and its radial distance. RESULTS Measurable disease was noted outside the prostatic capsule in 185 of 712 (26.0%) specimens. All preoperative parameters except ultrasound volume were able to predict the presence of ECE. However, none of them was predictive of the radial ECE distance. In this group, the median and the range of the maximum depth of invasion (radial extension from the capsule) were 2.00 and 0.5-12.00 mm, respectively. The mean radial distance from the capsule was 2.93 mm, SD ± 2.286 mm. All subgroups had some patients with radial extension ranging from 0-2 mm, 2-5 mm, to > 5 mm. Only patients with a prostate-specific antigen of 0-4 ng/mL had no extension ≥ 5 mm. CONCLUSIONS This is the largest series in the literature thus far that quantitatively assesses radial extracapsular extension. Coverage of subclinical disease must be addressed carefully before successful implementation of intensity-modulated radiation therapy, brachytherapy, or prostatectomy in order to avoid geographical miss. [ABSTRACT FROM AUTHOR]

Intensity modulated radiation therapy (IMRT), a new form of three-dimensional conformal radiation therapy (3DCRT), optimizes the concept of computer-controlled radiation deposition in tumor (target) while sparing adjacent normal structures. A retrospective review was done on the initial 185 patients with tumors in different sites including prostate cancer, head and neck cancer, pediatric tumors, adult brain tumors, and previously irradiated recurrent tumors treated with IMRT. Preliminary findings indicate that IMRT is a new clinically feasible tool in radiation oncology. Treatment-related morbidity profile was favorable. Tumor response, local control, and the ability to palliate previously irradiated patients are encouraging. Intensity modulated radiation therapy will allow dose escalation, leading to better tumor control. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine if intensity modulated radiation therapy (IMRT) offers a better treatment plan compared to conventional radiotherapy for patients with pectus excavatum desiring breast-conserving therapy and to assess the feasibility of simultaneous modulated accelerated radiation therapy (SMART) boost. A patient with pectus excavatum desired breast-conserving therapy for her early stage breast cancer. She underwent lumpectomy and axillary lymph node dissection followed by chemotherapy. She was then referred for radiotherapy. A breast board (Med-Tec) with aquaplast body cast was used to limit the movement of the patient, chest wall, and breasts before planning a computed tomography (CT) scan. IMRT including dose-volume histogram (DVH) was compared to that of the conventional plan using parallel opposed tangential beams with a 15-degree wedge pair. Forty-five gray was prescribed to the whole breast to each plan, while 50 Gy was prescribed to the tumor bed using IMRT with SMART boost in 25 fractions over 5 weeks. The coverage of the whole breast was adequate for both plans. IMRT allowed a more homogeneous dose distribution within the breast at the desired dose range. With IMRT there is less volume of ipsilateral lung receiving the radiation dose that is above the tolerance threshold of 15 Gy when compared to that of the conventional plan. However, there is more volume of surrounding normal tissues (the heart, spinal cord, and contralateral breast and lung) receiving low-dose irradiation when IMRT was employed. SMART boost was feasible, allowing a mean dose of 57 Gy to be delivered to the tumor bed simultaneously along with the rest of the breast in 5 weeks. IMRT is feasible in treating early breast cancer patients with pectus excavatum by decreasing the ipsilateral lung volume receiving high-dose radiation when compared to the conventional method. SMART boost shortens the overall treatment time that may have potential radiobiological benefit. [ABSTRACT FROM AUTHOR]

Trimodality therapy is the standard of care for locally advanced resectable esophageal cancer (EC) but carries morbidity and mortality risks; thus, therapy at high-volume facilities (HVFs) may offer advantages. This investigation studied postoperative outcomes and overall survival (OS) in EC patients receiving trimodality therapy at HVFs versus lower-volume facilities (LVFs). The National Cancer Data Base was queried for patients with locally advanced EC receiving trimodality therapy. HVFs referred to the 90th percentile of case volume. Multivariate logistic regression determined factors associated with treatment at HVFs, the Kaplan–Meier analysis compared OS between the HVF and LVF groups, and the Cox proportional hazards modeling determined variables associated with OS. Sensitivity analysis evaluated the impact of varying the HVF definition cutoff on OS. A total of 3,229 patients met study criteria, including 330 (10%) treated at HVFs and 2,899 (90%) at LVFs. Treatment at HVFs was associated with decreased 30-day mortality (1.2% vs. 3.3%, P  = 0.044) and trends toward lower 90-day mortality (4.8% vs. 7.8%, P  = 0.055) and the length of postoperative hospitalization (11.2 vs. 12.3d, P  = 0.059). HVF patients experienced higher median OS (55 vs. 36 months, P  = 0.004), which also independently correlated on the Cox multivariate analysis (P  = 0.001). Sensitivity analysis showed similar results as the HVF/LVF cutoff was decreased until the 80th percentile. This is the first study demonstrating that the trimodality management of EC at HVFs is associated with improved postoperative outcomes and survival. These data have implications for multidisciplinary oncologic providers, in addition to patient counseling by both referring and treating clinicians. [ABSTRACT FROM AUTHOR]

Highlights • 17% of patients achieved a pathologic complete response (pCR). • 37% achieved pathologic nodal clearance (PNC). • Patients who had pCR had superior overall survival compared all patients. • There was no improvement in OS with higher radiation therapy dose. Abstract Purpose From prospective studies, pathologic nodal clearance (PNC, ypN0) and pathologic complete response (pCR, ypT0N0) correlate with overall survival (OS) following neoadjuvant chemoradiation for cN2 non-small cell lung cancer (NSCLC). Contemporary cooperative group trials attempt to increase radiation doses to achieve nodal clearance and/or pCR. However, long-term comparative outcomes of dose-escalated neoadjuvant chemoradiation are lacking. The goal of this study was to evaluate rates of PNC and pCR in a large population of cN2 NSCLC, predictors thereof, and long-term outcomes thereafter. Methods The National Cancer Database was queried (2004–2015) for histologically-confirmed cT1-4N2M0 NSCLC undergoing neoadjuvant chemoradiation followed by lobectomy. Statistics included multivariable logistic regression, Kaplan-Meier OS analysis before and following propensity matching, Cox proportional hazards modeling, and sensitivity analysis when varying neoadjuvant radiation dose. Results Of 1750 patients, the pCR and PNC rates were 17% and 37%, respectively. Radiation dose >54 Gy independently predicted for pCR. Patients achieving pCR experienced significantly higher OS than non-pCR cases (p < 0.001) and ypT + ypN0 cases (p < 0.001). In the subset of non-PNC patients, there was a trend towards higher OS in patients in whom ypT0 was achieved (p = 0.059). On sensitivity analysis, when separating the cohort into doses of 45.0–50.4 Gy, 50.5–54.0 Gy, 54.1–59.4 Gy, and >59.4 Gy, 30-day mortality rates in the respective groups were 2.9%, 1.8%, 1.2%, and 3.4%. Conclusions Although neoadjuvant dose-escalation increases pCR rates, there is no OS benefit with dose-escalation, and high dose-escalation (i.e., >59.4 Gy) was associated with numerically higher mortality rates, indicating the importance of careful multidisciplinary discussion. [ABSTRACT FROM AUTHOR]

• In modern practice, patients age ≥70 with T1N0 ER/PR + HER2- breast cancer who are treated with breast conserving surgery and endocrine therapy have been considered candidates for omission of radiotherapy. • Recurrence score (RS) is predictive for prognostic benefit of radiotherapy in patients age ≥70 years. • There is an overall survival benefit with the use of radiotherapy in patients with RS ≥11 but not in patients with RS < 11. • Assessment of RS in patients age ≥70 years is recommended with consideration of RT when RS is ≥11. Based on the results of the Cancer and Leukemia Group B (CALGB) 9343 trial, patients age ≥70 with T1N0 hormone receptor positive (ER/PR+), human epidermal growth factor receptor-2 negative (HER2-) breast cancer who are treated with breast conserving surgery (BCS) and endocrine therapy (ET) are candidates for omission of radiotherapy (RT). Because the CALGB 9343 trial did not stratify based on recurrence score (RS) test (Oncotype Dx), we conducted the present retrospective study to determine whether RS is predictive of who may benefit from RT following BCS in this cohort. The National Cancer Database (NCDB) was queried (2004–2017) for patients age ≥ 70 with pT1N0 ER+/PR + HER2- breast cancer treated with BCS and ET. Patients were stratified based on their RS (low risk [LR] = 1–10, intermediate risk [IR] = 11–25, high risk [HR] = 26–99). Propensity score matching (PSM) created 1:1 matched cohorts of patients who received radiotherapy and those who did not. Kaplan-Meier analysis evaluated overall survival (OS). Univariable (UVA) and multivariable (MVA) Cox proportional hazard analyses identified clinical and treatment factors prognostic for OS. A total of 11,891 patients met the selection criteria: 3364 in the LR cohort, 7305 in the IR cohort, and 1222 in the HR cohort. A total of 79 % received RT: 77 % in the LR cohort, 79 % in the IR cohort, and 85 % in the HR cohort. Because PSM could not be efficiently performed in the HR cohort alone, the IR and HR cohort were merged (IRHR) for matching. After PSM, the 5-year OS in the LR cohort was 91 % for those who received RT and 89 % for those who did not (p = 0.605). In the IRHR cohort, the 5-year OS was 91 % for those who received RT and 87 % for those who did not (p = 0.003). On MVA in the LR cohort, RT (p = 0.727) was not predictive of improved OS. On MVA in the IRHR cohort, RT (p = 0.010) was a positive prognostic factor for OS. In this older cohort of patients, there is an OS benefit with the use of RT in patients with IRHR RS but not in patients with LR RS. Pending prospective evaluation, assessment of RS in this older subset of patients is recommended with consideration of RT when RS is ≥11. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: Endorectal balloons (ERBs) are being used in prostate radiotherapy for prostate immobilization and rectal wall (Rwall) sparing. Some of their aspects, however, have been questioned, like patient’s tolerance and their value in modern high-precision radiotherapy. This paper gives an overview of published data concerning ERB application in prostate radiotherapy. Materials and methods: Systematic literature review based on PubMed/MEDLINE database searches. Results: Overall, ERBs are tolerated well, although patients with pre-existing anorectal disease have an increased risk of developing ERB-related toxicity. Planning studies show reduced Rwall and anal wall (Awall) doses with ERB application. Clinical data, however, are scarce, as only one study shows reduced late rectal damage. There is no consensus about the immobilizing properties of ERBs and it is recommended to use additional set-up and correction protocols, especially because there are potential pitfalls. Conclusion: ERBs seem well-tolerated and in planning studies reduce anorectal wall doses. This may lead to reduced anorectal toxicity, although clinical studies are warranted to confirm this hypothesis and to further investigate the immobilizing properties of ERBs, preferably in combination with advanced techniques for position verification. [Copyright &y& Elsevier]

• PMRT was not associated with an overall survival benefit in all patients. • Number of lymph nodes removed was not associated with overall survival. • PMRT improved overall survival in patients with cT3-4 and cN3 disease. The utility of post-mastectomy radiotherapy (PMRT) in women with a nodal complete response (CRn) to neoadjuvant chemotherapy (NAC) is unknown. The NSABP B-51 trial is evaluating this question, but has not reported results thus far. Therefore, we sought to answer this question with the National Cancer Database. The National Cancer Database was queried for women with cT1–4N1-3M0 breast cancer who had undergone NAC and were ypN0 upon mastectomy. Statistics included multivariable logistic regression, Kaplan-Meier overall survival (OS) analysis, Cox proportional hazards modeling, and construction of forest plots. Of 14,690 women, 10,092 (69%) underwent adjuvant PMRT and 4598 (31%) did not. The median follow-up was 55.6 months. In all patients, the 10-year OS was 76.3% for PMRT and 78.6% without (p = 0.412). There were no notable effects of PMRT on OS based on age or the axillary management (number of nodes removed). Specifically, in the NSABP B-51 population of cT1–3 cN1 patients, the 10-year OS was 82.6% for PMRT and 80.0% without (p = 0.250). PMRT benefitted women with increasing cT stage (i.e. cT3–4), increasing ypT stages (with the exception of ypT4 potentially owing to small sample sizes), and cN3 cases (p < 0.05 for all). In the absence of published results from NSABP B-51, this assessment of over 14,000 women from a contemporary US database revealed that PMRT may be most useful for a "moderately-high" risk group – women with more advanced primary and/or nodal disease at diagnosis, yet with tumor biology favorable enough that the disease does not progress or remain stable after NAC. The OS findings notwithstanding, this study cannot exclude potential differences between groups in recurrence-free survival, which is the primary endpoint of NSABP B-51, While the results of the NSABP B-51 will confirm optimal management for patients with limited nodal disease having a CRn following NAC, the present results suggest PMRT should remain the standard of care for more advanced disease than NSABP B-51 eligibility criteria. [ABSTRACT FROM AUTHOR]

• Breast tubular carcinoma is a low-grade histology with favorable prognosis. • Radiotherapy is associated with overall survival benefit for tubular carcinoma. • Adjuvant radiotherapy should remain standard of care for tubular carcinoma. Tubular carcinoma (TC) is an invasive breast cancer with favorable prognosis. While pathology-specific guidelines exist for TC regarding adjuvant chemotherapy and endocrine therapy, no recommendations exist regarding locoregional treatment based on tumor histology. Prognostic impact of radiotherapy for patients with TC remains unclear. The National Cancer Database was queried (2004–2015) for patients with pN0M0 TC who underwent lumpectomy. Chi-square testing compared categorized variables between those who did and did not receive radiotherapy. Kaplan–Meier analysis evaluated overall survival (OS). Cox proportional hazard analysis identified variables prognostic for OS. Patients were divided into age cohorts ≤60 years and >60 years. Propensity score matching (PSM) was utilized to create similar cohorts. 9705 patients met selection criteria; 6182 (75.1%) received radiotherapy while 2045 (24.9%) did not. After PSM, radiotherapy (HR 0.582; 95% CI 0.494–0.686) and endocrine therapy (HR 0.737; 95% CI 0.623–0.872) were favorable prognostic factors on multivariate Cox regression analysis while age > 60 years (HR 5.131; 95% CI 3.753–7.016), Black race (HR 1.445; 95% CI 1.016–2.055), and Charlson-Deyo comorbidity score > 0 (HR 1.708; 95% CI 1.403–2.079) were unfavorable prognostic factors. After PSM, 5-year OS was 91.7% for those who received radiotherapy and 84.5% for those who did not; 10-year OS was 76.1% and 64.1%, respectively (p < 0.001). This is the largest study to date on TC and the prognostic impact of adjuvant radiotherapy. Postoperative radiotherapy is a favorable prognostic factor for OS in patients with pN0M0 TC, suggesting adjuvant radiotherapy should remain standard of care in these patients. [ABSTRACT FROM AUTHOR]

Highlights • Use of PMRT is low for all node negative TNBC patients. • Higher PMRT rates are observed for patients with T3 or T4 disease. • PMRT was associated with improved OS only for T3 patients. Abstract Purpose The use of post-mastectomy radiation therapy (PMRT) for patients with node-negative, triple negative breast cancer (TNBC) is controversial. This study of a large, contemporary US database described national practice patterns and addressed the impact of PMRT on survival for patients with node-negative TNBC. Methods The National Cancer Data Base was queried (2004–2014) for women with non-metastatic TNBC with pT1-4N0M0 disease undergoing mastectomy. Use of PMRT was assessed. Multivariable logistic regression ascertained factors associated with PMRT use. The Kaplan–Meier analysis evaluated overall survival (OS) between patients managed with either PMRT or observation following mastectomy when stratifying by pT stage. Cox proportional hazards modeling determined variables associated with OS. Results A total of 14,464 patients met the selection criteria; of these, 1,569 (10.8%) received PMRT, whereas 12,895 (89.2%) did not receive PMRT. Use of PMRT varied significantly with pT stage, with only 5.7% of T1 patients undergoing PMRT, while 51.6% of patients with T3 disease underwent PMRT. Use of PMRT was associated with superior OS for patients with pT3 disease but not for patients with other T stages. Greater age was associated with decreased likelihood of PMRT use, while increased T stage and positive surgical margins were associated with use of PMRT. On multivariate analysis, increased age, T stage, and positive surgical margins were associated with worse OS. Conclusions In the largest study to date evaluating the use of PMRT in patients with node-negative TNBC, the use of PMRT was low in patients with T1 and T2 disease. Additionally, while an OS benefit was observed with the use of PMRT in patients with T3 disease, there was no benefit with the use of PMRT in other T stage groups. Further prospective studies are recommended to further elucidate the benefit on PMRT in patients with node-negative TNBC. [ABSTRACT FROM AUTHOR]

Abstract Introduction Life expectancy of patients with limited-stage small cell lung cancer (LS-SCLC) continues to rise; thus, characterization of long-term toxicities is essential. Although there are emerging data linking cardiac irradiation doses with survival for non-small cell lung cancer, there are currently minimal data on cardiac-specific mortality (CSM) in LS-SCLC. The goal of this investigation was to evaluate CSM between left- and right-sided cases. Methods The Surveillance, Epidemiology, and End Results database was queried for stage I–III primary SCLC patients receiving radiotherapy; CSM was compared between left- and right-sided diseases. Accounting for mortality from other causes, Gray’s test compared cumulative incidences of CSM between both groups. Multiple multivariate models examined the independent effect of laterality on CSM, including the Fine and Gray competing risk model and the Cox proportional hazards model. Results Of 19,692 patients, 7991 (41%) were left-sided and 11,701 (59%) were right-sided. Left-sided patients experienced significantly higher CSM overall (3.3% vs. 2.6%, p = 0.004). Laterality was an independent predictor of CSM in the overall population in the Fine and Gray competing risk model (p = 0.006) as well as the Cox proportional hazards model (p = 0.007). The overall hazard ratio for CSM by disease laterality was 1.27 (95% confidence interval, 1.08–1.50). Laterality had no statistical association with non-cardiac mortality in the Fine and Gray competing risk model (p = 0.130). Conclusions Although causation between radiotherapy and CSM in LS-SCLC cannot be stated based on these data, we encourage clinical attentiveness to cardiac-sparing radiotherapy for LS-SCLC, along with further investigation evaluating dosimetric correlates for cardiotoxicity. [ABSTRACT FROM AUTHOR]

Purpose: To use the Surveillance, Epidemiology, and End Results (SEER) database to compare cardiac-specific mortality (CSM) between left- and right-sided locally advanced non-small cell lung cancer (LA-NSCLC) patients treated with definitive radiation therapy; and to stratify these patients over fixed time intervals to assess for differences in events by treatment era.Methods and Materials: The SEER database was queried for patients with stage III NSCLC who received radiation therapy to compare CSM between left- and right-sided primary cases at 5 time intervals: 1988-1992, 1993-1997, 1998-2002, 2003-2007, and 2008-2012. Cumulative incidence of CSM was compared between left- and right-sided patients using Gray's test. The multivariate Fine and Gray competing risk model was used to compare CSM while accounting for other-cause mortality.Results: Of 884,610 lung cancer patients, 52,624 met inclusion criteria; of these, 31,549 (60%) were right-sided and 21,075 (40%) were left-sided. When evaluating CSM in each of the 5 time periods, the overall incidence of CSM decreased over time. There was a statistically significant (P<.05) difference based on laterality in all time periods except 1988-1992 (P=.14). The subdistribution hazard ratio for CSM based on disease laterality in all time periods was 1.30 (95% confidence interval 1.18-1.42) and did not discernibly differ by time interval. On multivariate analysis using the Fine and Gray competing risk model, left-sided laterality independently predicted for CSS from 1993 to 2007 (P<.05).Conclusions: Cardiac-specific mortality has decreased over time, and left-sided disease independently predicted for CSS during 1993-2007 but not 2008-2012. The time course of cardiac mortality seems to be early, consistent with other studies. These findings underscore the importance of minimizing cardiac irradiation during radiation treatment planning. [ABSTRACT FROM AUTHOR]

Abstract: Aims: To analyse the outcomes and to evaluate the prognostic factors involved in the re-irradiation of locally recurrent nasopharyngeal carcinoma (NPC) using intensity-modulated radiotherapy (IMRT). Materials and methods: A retrospective analysis of 239 NPC patients with local recurrence who were re-irradiated with IMRT between 2001 and 2008 was conducted. The distribution of disease re-staging was 5.4% for stage I, 18.4% for stage II, 29.7% for stage III and 46.4% for stage IV. Cisplatin-based chemotherapy was administered to 117 patients (49.0%) in addition to the IMRT. Results: The mean D95 and the V95 of the gross tumour volume (GTV) were 66.78Gy and 98.61%, respectively. The mean dose to the GTV was 70.04Gy (61.73–77.54Gy). The 5 year overall survival, local recurrence-free survival, distant metastasis-free survival and disease-free survival were 44.9, 85.8, 80.6 and 45.4%, respectively. In a univariate analysis, patient age, recurrent T (rT), recurrent N (rN), recurrent stage, tumour volume, mean dose and mean fractional dose of the GTV were significant prognostic factors for overall survival. In a multivariate analysis, only patient age, rN stage, recurrent stage, mean fractional dose and tumour volume remained significant for overall survival. Conclusions: Re-irradiation using IMRT is available to improve local tumour control and to prolong patients’ survival. A smaller tumour volume, higher fractional dose, younger patient ages, lower rN0 stage and early recurrent stage are all independent prognostic factors for overall survival of recurrent NPC. It is of clinical importance to select the appropriate recurrent NPC cases for salvage re-irradiation by IMRT. [Copyright &y& Elsevier]

Purpose: To compile and review data on radiation proctopathy in the treatment of prostate cancer with respect to epidemiology, clinical manifestations, pathogenesis, risk factors, and treatment. Methods: Medical literature databases including PubMed and Medline were screened for pertinent reports, and critically analyzed for relevance in the scope of our purpose. Results: Rectal toxicity as a complication of radiotherapy has received attention over the past decade, especially with the advent of dose-escalation in prostate cancer treatment. A number of clinical criteria help to define acute and chronic radiation proctopathy, but lack of a unified grading scale makes comparing studies difficult. A variety of risk factors, related to either radiation delivery or patient, are the subject of intense study. Also, a variety of treatment options, including medical therapy, endoscopic treatments, and surgery have shown varied results, but a lack of large randomized trials evaluating their efficacy prevents forming concrete recommendations. Conclusion: Radiation proctopathy should be an important consideration for the clinician in the treatment of prostate cancer especially with dose escalation. With further study of possible risk factors, the advent of a standardized grading scale, and more randomized trials to evaluate treatments, patients and physicians will be better armed to make appropriate management decisions. [Copyright &y& Elsevier]

Purpose: To explore long-term immune responses after combined radio-gene-hormonal therapy. Methods and Materials: Thirty-three patients with prostate specific antigen 10 or higher or Gleason score of 7 or higher or clinical stage T2b to T3 were treated with gene therapy that consisted of 3 separate intraprostatic injections of AdHSV-tk on Days 0, 56, and 70. Each injection was followed by 2 weeks of valacyclovir. Intensity-modulated radiation therapy was delivered 2 days after the second AdHSV-tk injection for 7 weeks. Hormonal therapy was initiated on Day 0 and continued for 4 months or 2.3 years. Blood samples were taken before, during, and after treatment. Lymphocytes were analyzed by fluorescent antibody cell sorting (FACS). Results: Median follow-up was 26 months (range, 4–48 months). The mean percentages of DR+CD8+ T cells were increased at all timepoints up to 8 months. The mean percentages of DR+CD4+ T cells were increased later and sustained longer until 12 months. Long-term (2.3 years) use of hormonal therapy did not affect the percentage of any lymphocyte population. Conclusions: Sustained long-term (up to 8 to 12 months) systemic T-cell responses were noted after combined radio-gene-hormonal therapy for prostate cancer. Prolonged use of hormonal therapy does not suppress this response. These results suggest the potential for sustained activation of cell-mediated immune responses against cancer. [Copyright &y& Elsevier]

Abstract: The use of an air-filled rectal balloon has been shown to decrease prostate motion during prostate radiotherapy. However, the perturbation of radiation dose near the air-tissue interfaces has raised clinical concerns of underdosing the prostate gland. The aim of this study was to investigate the dosimetric effects of an air-filled rectal balloon on the rectal wall/mucosa and prostate gland. Clinical rectal toxicity and dose-volume histogram (DVH) were also assessed to evaluate for any correlation. A film phantom was constructed to simulate the 4-cm diameter air cavity created by a rectal balloon. Kodak XV2 films were utilized to measure and compare dose distribution with and without air cavity. To study the effect in a typical clinical situation, the phantom was computed tomography (CT) scanned on a Siemens DR CT scanner for intensity-modulated radiation therapy (IMRT) treatment planning. A target object was drawn on the phantom CT images to simulate the treatment of prostate cancer. Because patients were treated in prone position, the air cavity was situated superiorly to the target. The treatment used a serial tomotherapy technique with the Multivane Intensity Modulating Collimator (MIMiC) in arc treatment mode. Rectal toxicity was assessed in 116 patients treated with IMRT to a mean dose of 76 Gy over 35 fractions (2.17-Gy fraction size). They were treated in the prone position, immobilized using a Vac-Lok™ bag and carrier-box system. Rectal balloon inflated with 100 cc of air was used for prostate gland immobilization during daily treatment. Rectal toxicity was assessed using modifications of the Radiation Therapy Oncology Group (RTOG) and late effects Normal Tissue Task Force (LENT) scales systems. DVH of the rectum was also evaluated. From film dosimetry, there was a dose reduction at the distal air-tissue interface as much as 60% compared with the same geometry without the air cavity for 15-MV photon beam and 2 × 2-cm field size. The dose beyond the interface recovered quickly and the dose reductions due to air cavity were 50%, 28%, 11%, and 1% at 2, 5, 10, and 15 mm, respectively, from the distal air-tissue interface. Evaluating the dose profiles of the more clinically relevant situation revealed the dose at air-tissue interface was approximately 15% lower in comparison to that without an air cavity. The dose built up rapidly so that at 1 and 2 mm, there was only an 8% and 5% differential, respectively. The dosimetric coverage at the depth of the posterior prostate wall was essentially equal with or without the air cavity. The median follow-up was 31.3 months. Rectal toxicity profile was very favorable: 81% (94/116) patients had no rectal complaint while 10.3% (12/116), 6.9% (8/116), and 1.7% (2/116) had grade 1, 2, and 3 toxicity, respectively. There was no grade 4 rectal toxicity. DVH analysis revealed that none of the patients had more than 25% of the rectum receiving 70 Gy or greater. Rectal balloon has rendered anterior rectal wall sparing by its dosimetric effects. In addition, it has reduced rectal volume, especially posterior and lateral rectal wall receiving high-dose radiation by rectal wall distension. Both factors may have contributed to decreased rectal toxicity achieved by IMRT despite dose escalation and higher than conventional fraction size. The findings have clinical significance for future very high-dose escalation trials whereby radiation proctitis is a major limiting factor. [Copyright &y& Elsevier]

: PurposeThere is an evolving role for combining radiotherapy (RT) with gene therapy in the management of prostate cancer. However, the clinical results of this combined approach are much needed. The preliminary results addressing the safety of this Phase I-II study combining RT and gene therapy (adenovirus/herpes simplex virus-thymidine kinase gene/valacyclovir with or without hormonal therapy) in the treatment of prostate cancer have been previously reported. We now report the prostate-specific antigen (PSA) response and biopsy data.: Methods and materialsThis trial was composed of three separate arms. Arm A consisted of low-risk patients (Stage T1-T2a, Gleason score <7, pretreatment PSA <10 ng/mL) treated with combined RT-gene therapy. A mean dose of 76 Gy was delivered to the prostate with intensity-modulated RT. They also received adenovirus/herpes simplex virus-thymidine kinase/valacyclovir gene therapy. Arm B consisted of high-risk patients (Stage T2b-T3, Gleason score >6, pretreatment PSA level >10 ng/mL) treated with combined RT-gene therapy and hormonal therapy (luteinizing hormone-releasing hormone agonist [30-mg Lupron, 4-month depot] and an antiandrogen [flutamide, 250 mg t.i.d. for 14 days]). Arm C consisted of patients with Stage D1 (positive pelvic lymph nodes) who received the same regimen as Arm B with the addition of 45 Gy to the pelvic lymphatics. PSA determination and biopsy were performed before, during, and after treatment. The American Society for Therapeutic Radiology and Oncology consensus definition (three consecutive rises in PSA level) was used to denote PSA failure.: ResultsFifty-nine patients (29 in Arm A, 26 in Arm B, and 4 in Arm C) completed the trial. The median age was 68 years (range, 39–85 years). The median follow-up for the entire group was 13.5 months (range, 1.4–27.8 months). Only Arm A patients were observed to have an increase in PSA on Day 14. The PSA then declined appropriately. All patients in Arm A (median follow-up, 13.4 months) and Arm B (median follow-up, 13.9 months) had biochemical control at last follow-up. Three patients in Arm C (with pretreatment PSA of 335, 19.6, and 2.5 ng/mL and a combined Gleason score of 8, 9, and 9 involving all biopsy cores) had biochemical failure at 3, 3, and 7.7 months. Two patients had distant failure in bone and 1 patient in the para-aortic lymph nodes outside the RT portal. Six to twelve prostate biopsies performed in these 3 patients revealed no evidence of residual carcinoma. In Arm A, biopsy showed no evidence of carcinoma in 66.7% (18 of 27), 92.3% (24 of 26), 91.7% (11 of 12), 100% (8 of 8), and 100% (6 of 6) at 6 weeks, 4 months, 12 months, 18 months, and 24 months after treatment, respectively. In Arm B, no evidence of carcinoma on biopsy was noted in 96% (24 of 25), 90.5% (19 of 21), 100% (14 of 14), 100% (7 of 7), and 100% (2 of 2), respectively, in the same interval after treatment.: ConclusionThis is the first reported trial of its kind in the field of prostate cancer that aims to expand the therapeutic index of RT by combining it with in situ gene therapy. The initial transient PSA rise in the Arm A patients may have been a result of local immunologic response or inflammation elicited by in situ gene therapy. Additional investigation to elucidate the mechanisms is needed. Hormonal therapy may have obliterated this rise in Arm B and C patients. The biopsy data were encouraging and appeared to show no evidence of malignancy earlier than historical data. Combined RT, short-course hormonal therapy, and in situ therapy appeared to provide good locoregional control but inadequate systemic control in patients with positive pelvic lymph nodes. Longer term use of hormonal therapy in addition to gene therapy and RT has been adopted for this group of patients to maximize both locoregional and systemic control. [Copyright &y& Elsevier]

: PurposeA pilot study was designed to evaluate the safety and efficacy of a novel regimen of hypofractionated intensity-modulated radiotherapy (RT) in the adjuvant treatment of primary glioblastoma multiforme (GBM). The rationale of the study was to combine the potential radiobiologic advantage of hypofractionation to GBM with a highly conformal radiotherapeutic technique. The study was designed to measure the acute and chronic morbidity of patients treated with this regimen, response of GBM to the treatment, overall survival, and time to disease progression after therapy completion.: Methods and materialsTwenty eligible patients were accrued between February 1999 and May 2000 for the study. All patients had Karnofsky performance scores of ≥70. All patients were treated with intensity-modulated RT using the NOMOS Peacock system. A dose of 50 Gy was delivered in 5-Gy daily fractions within 2 weeks to enhancing primary disease, residual tumor, or surgical cavity. Simultaneously, 30 Gy was prescribed in 3-Gy daily fractions to surrounding edema. The time to progression was measured with serial neurologic examinations and MRI or CT scans after RT completion. Acute and late toxicity was graded using Radiation Therapy Oncology Group neurotoxicity scores.: ResultsOf the 20 patients, 18 were evaluated for outcome. The median time to disease progression was 6 months after RT completion. The median overall survival was 7 months after treatment completion. All recurrences were within 2 cm of the operative bed. Neurotoxicity during therapy was minimal, with all patients experiencing Grade 0 or 1 toxicity. Late toxicity included 10 patients with Grade 0, 2 patients with Grade 2, and 3 patients with Grade 4 toxicity, manifesting as brain necrosis requiring surgical reexcision. The survival of the 3 patients with brain necrosis was 23, 20, and 9 months. Mortality in all cases was the result of tumor recurrence, with no mortality resulting from brain necrosis.: ConclusionThis regimen of hypofractionated intensity-modulated RT did not improve the time to disease progression or overall survival compared with historical experience using conventional fractionation. However, the treatment duration was reduced from 6 weeks to 2 weeks, which may be of palliative benefit in certain subsets of patients. This treatment regimen demonstrated a greater incidence of brain necrosis requiring surgical intervention; however, the 3 patients experiencing this toxicity had longer survival times. Future investigation may be useful to determine which fraction size may be optimal for GBM when highly conformal RT is used in the adjuvant setting. [Copyright &y& Elsevier]

: PurposeTo report our initial experience on the feasibility, toxicity, and tumor control using intensity-modulated radiotherapy (IMRT) for retreatment of recurrent nasopharyngeal carcinoma (NPC).: Methods and materialsA total of 49 patients with locoregional recurrent carcinoma in the nasopharynx were treated with IMRT between January 2001 and February 2002 at the Sun Yat-Sen University Cancer Center, Guangzhou, China. The average time to the nasopharyngeal recurrence was 30.2 months after initial conventional RT. The median isocenter dose to the nasopharynx was 70 Gy (range 60.9–78.0) for the initial conventional RT. All patients were restaged at the time of recurrence according to the 1992 Fuzhou, China staging system on NPC. The number of patients with Stage I, II, III and IV disease was 4, 9, 10, and 26, respectively. T1, T2, T3, and T4 disease was found in 4, 9, 11, and 25 patients, respectively. N0, N1, N2, and N3 disease was found in 46, 2, 0, and 1 patient, respectively. Invasion of the nasal cavity, maxillary sinus, ethmoid sinus, sphenoid sinus, and cavernous sinus and erosion of the base of the skull was found in 8, 1, 3, 8, 15, and 20 patients, respectively. The gross tumor volume (GTV) was contoured according to the International Commission on Radiation Units and Measurements (ICRU) Report 62 guidelines. The critical structures were contoured, and the doses to critical structures were constrained according to ICRU 50 guidelines. The GTV in the nasopharynx and positive lymph nodes in the neck received a prescription dose of 68–70 Gy and 60 Gy, respectively. All patients received full-course IMRT. Three patients who had positive lymph nodes were treated with five to six courses of chemotherapy (cisplatin + 5-fluorouracil) after IMRT.: ResultsThe treatment plans showed that the percentage of GTV receiving 95% of the prescribed dose (V95-GTV) was 98.5%, and the dose encompassing 95% of GTV (D95-GTV) was 68.1 Gy in the nasopharynx. The mean dose to the GTV was 71.4 Gy. The average doses of the surrounding critical structures were much lower than the tolerable thresholds. At a median follow-up of 9 months (range 3–13), the locoregional control rate was 100%. Three cases (6.1%) of locoregional residual disease were seen at the completion of IMRT, but had achieved a complete response at follow-up. Three patients developed metastases at a distant site: two in the bone and one in the liver and lung at 13 months follow-up. Acute toxicity (skin, mucosa, and xerostomia) was acceptable according to the Radiation Therapy Oncology Group criteria. Tumor necrosis was seen toward the end of IMRT in 14 patients (28.6%).: ConclusionThe improvement in tumor target coverage and significant sparing of adjacent critical structures allow the feasibility of IMRT as a retreatment option for recurrent NPC after initial conventional RT. This is the first large series using IMRT to reirradiate local recurrent NPC after initial RT failed. The treatment-related toxicity profile was acceptable. The initial tumor response/local control was also very encouraging. In contrast to primary NPC, recurrent NPC reirradiated with high-dose IMRT led to the shedding of tumor necrotic tissue toward the end of RT. More patients and longer term follow-up are warranted to evaluate late toxicity and treatment outcome. [Copyright &y& Elsevier]

Purpose: The advent of widespread prostate-specific antigen screening has resulted in more younger, potent men being diagnosed with early-stage, organ-confined prostate cancer amenable to definitive surgery. Nerve-sparing prostatectomy is a relatively new surgical advance in the treatment of prostate cancer. Very few data exist on the effect of postoperative radiotherapy (RT) on erectile function after nerve-sparing prostatectomy. They are based on conventional techniques using moderate doses of radiation, 45–54 Gy. Intensity-modulated RT (IMRT) is becoming more widespread because it allows dose escalation with increased sparing of the surrounding normal tissue. We investigated the effect of postprostatectomy, high-dose IMRT on patients’ erectile function.Methods and Materials: A review of patient records found 51 patients treated between April 1998 and December 2000 with IMRT after unilateral or bilateral nerve-sparing prostatectomy. The pathologic disease stage in these patients was T2 in 47.4% and T3 in 52.6%. Postoperatively, 4 patients received hormonal ablation consisting of one injection of Lupron Depot (30 mg) 2 months before RT. The median age was 65 years (range 46–77) at the time of RT. The prescribed dose was 64 Gy (range 60–66). The mean dose was 69.6 Gy (range 64.0–72.3). Erectile function was assessed before and after RT by questionnaires. Sexual potency was defined as erectile rigidity adequate for vaginal penetration.Results: Of the 51 patients, 18 (35.3%) maintained their potency and 33 (64.7%) became impotent after nerve-sparing prostatectomy. Patients who underwent bilateral nerve-sparing prostatectomy had higher rates of postoperative potency than did those who underwent unilateral nerve-sparing surgery (72.2% vs. 27.8%; p = 0.025). The follow-up for the entire group was 19.5 months. All 18 patients (100%) who were potent postoperatively remained potent after RT. The median follow-up for the 18 potent patients was 27.2 months, significantly longer than that of the impotent group, 13.0 months (p <0.001).Conclusion: This is the first report on the effects of dose-escalated IMRT on men who have undergone nerve-sparing prostatectomy. Despite the high dose (mean dose 69.6 Gy) to the prostate bed and nerves, postoperative IMRT had no negative effect on erectile function for the patients who remained potent after nerve-sparing prostatectomy. Longer term follow-up and a larger cohort of patients are warranted to confirm these findings. [Copyright &y& Elsevier]

Purpose: To assess the safety and efficacy of intensity-modulated radiation therapy (IMRT) in the treatment of intracranial meningioma.Methods and Materials: Forty patients with intracranial meningioma (excluding optic nerve sheath meningiomas) were treated using IMRT with the NOMOS Peacock system between 1994 and 1999. Twenty-five patients received IMRT after surgery either as adjuvant therapy for incomplete resection or for recurrence, and 15 patients received definitive IMRT after presumptive diagnosis based on imaging. Thirty-two patients had skull base lesions, and 8 had nonskull base lesions. The prescribed dose ranged from 40 to 56 Gy (median 50.4 Gy) at 1.71 to 2 Gy per fraction, and the volume of the primary target ranged from 1.55 to 324.57 cc (median 20.22 cc). The mean dose to the target ranged from 44 to 60 Gy (median 53 Gy). Follow-up ranged from 6 to 71 months (median 30 months). Acute and chronic toxicity were assessed using Radiation Therapy Oncology Group (RTOG) morbidity criteria and tumor response was assessed by patient report, examination, and imaging. Overall survival, progression-free survival, and local control were calculated using the Kaplan-Meier method.Results: Cumulative 5-year local control, progression-free survival, and overall survival were 93%, 88%, and 89%, respectively. Two patients progressed after IMRT, one locally and one distantly. Each was treated with IMRT after multiple recurrences of benign meningioma over many years. Both were found to have malignant meningioma at the time of relapse after IMRT, and it is likely their tumors had already undergone malignant change by the time IMRT was given. Defined normal structures generally received a significantly lower dose than the target. The most common acute central nervous system (CNS) toxicity was mild headache, usually relieved with steroids. One patient experienced RTOG Grade 3 acute CNS toxicity, and 2 experienced Grade 3 or higher late CNS toxicity, with one possible treatment-related death. No toxicity was observed with mean doses to the optic nerve/chiasm up to 47 Gy and maximum doses up to 55 Gy.Conclusion: IMRT is a promising new technology that is safe and efficacious in the primary and adjuvant treatment of intracranial meningiomas. A history of local aggression may indicate malignant degeneration and predict a poorer outcome. Toxicity data are encouraging, but the potential for serious side effects exists, as demonstrated by one possible treatment-related death. Larger cohort and longer follow-up are needed to better define efficacy and late toxicity of IMRT. [Copyright &y& Elsevier]

The implementation of intensity-modulated radiation therapy (IMRT) is the result of advances in imaging, radiotherapy planning technologies, and computer-controlled linear accelerators. IMRT allows both conformal treatment of tumors and conformal avoidance of the surrounding normal structures. The first patient treated with Peacock IMRT at Baylor College of Medicine took place in March 1994. To date, more than 1500 patients have been treated with IMRT; more than 700 patients were treated for prostate cancer. Our experience in treating prostate cancer with IMRT was reviewed. Patient and prostate motions are important issues to address in delivering IMRT. The Vac-Lok bag-and-box system, as well as rectal balloon for immobilization of patient and prostate gland, respectively, are employed. Treatment planning also plays a very important role. IMRT as a boost after conventional external beam radiotherapy is not our treatment strategy. To derive maximal benefits with this new technology, all patients received full course IMRT. Three separate groups of patients receiving (1) primary IMRT, (2) combined radioactive seed implant and IMRT, and (3) post-prostatectomy IMRT were addressed. Overall, toxicity profiles in these patients were very favorable. IMRT has the potential to improve treatment outcome with dose escalation while minimizing treatment-related toxicity. [Copyright &y& Elsevier]