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Breast cancer is diagnosed in nearly 3 million people worldwide. Radiation therapy is an integral component of disease management for patients with breast cancer, and is used after breast-conserving surgery or a mastectomy to reduce the risk of a local recurrence. The following review describes the methods used to personalize radiation therapy by optimizing patient selection, using advanced treatment techniques to lessen the radiation dose to normal organs, and using hypofractionation in order to shorten the duration of radiation treatment. [ABSTRACT FROM AUTHOR]

Background: This study quantified clinical outcomes by molecular subtype of metastatic breast cancer (BC) following whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS). Doing so is important for patient counseling and to assess the potential benefit of combining targeted therapy and brain radiotherapy for certain molecular subtypes in ongoing trials. Materials and methods: The National Cancer Database was queried for BC (invasive ductal carcinoma) cases receiving brain radiotherapy (divided into WBRT and SRS). Statistics included multivariable logistic regression to determine factors associated with SRS delivery, Kaplan-Meier analysis to evaluate overall survival (OS), and Cox proportional hazards modeling. Results: Of 1,112 patients, 186 (16.7%) received SRS and 926 (83.3%) underwent WBRT. Altogether, 410 (36.9%), 195 (17.5%), 162 (14.6%), and 345 (31.0%) were ER+/HER2-, ER+/HER2+, ER-/HER2+, and ER-/HER2-, respectively. In the respective molecular subtypes, the proportion of subjects who underwent SRS was 13.4%, 19.4%, 24.1%, and 15.7%. Respective OS for WBRT patients were 12.9, 22.8, 10.6, and 5.8 months; corresponding figures for the SRS cohort were 28.3, 40.7, 15.0, and 12.9 months (p < 0.05 for both). When comparing OS between treatment different histologic subtypes, patients with ER-/HER2+ and ER-/HER2- disease had worse OS than patients with ER+/HER2- disease, for both patients treated with SRS and for patients treated with WBRT. Conclusions: Molecular subtype may be a useful prognostic marker to quantify survival following SRS/WBRT for metastatic BC. Patients with HER 2-enriched and triple-negative disease had the poorest survival following brain irradiation, lending credence to ongoing studies testing the addition of targeted therapies for these subtypes. [ABSTRACT FROM AUTHOR]

• mMGMT is prognostic for patients with Grade 3 Glioma. • mMGMT is predictive for OS benefit with chemoRT or RT. • 5% of patients with Grade 3 Glioma have the MGMT test. Grade 3 gliomas are aggressive primary brain tumors. Promoter methylation of methyl guanine methyl transferase (MGMT) has been associated with a favorable prognosis in patients with glioblastoma, but the impact of MGMT promoter methylation in patients with grade 3 gliomas is less clear. The purpose of the present study was to evaluate the utilization of MGMT testing in patients with Grade 3 glioma, as well its prognostic and predictive value. The National Cancer Database (NCDB) was queried (2004–2016) for patients with newly diagnosed grade 3 glioma without 1p19q codeletion. Statistics included Kaplan-Meier overall survival (OS) analysis, along with Cox proportional hazards modeling. Of 20,488 total patients, 1,209 (5.0%) had MGMT testing. Of these patients, 561 (46.4%) were MGMT methylated (mMGMT), and 648 (53.6%) were MGMT unmethylated (uMGMT). mMGMT patients experienced greater median overall survival (OS) than both uMGMT patients as well as patients with no MGMT status reported (p < 0.05 for both). mMGMT was associated with improved OS for patients receiving adjuvant chemoradiation or adjuvant radiation, but not for patients receiving adjuvant chemotherapy or no adjuvant treatment. This is the largest study to date describing the utilization of and outcomes for mMGMT patients with grade 3 glioma. The present results demonstrate that mMGMT is a prognostic factor and possibly a predictive biomarker, and is currently under-utilized within the US. MGMT methylation status could be used to risk-stratify and select patients for treatment intensification. The present study is the largest of its kind to examine the prognostic and predictive impact of MGMT methylation (mMGMT) amongst patients with Grade 3 Glioma. The results suggest that mMGMT is prognostic, as amongst all patients, mMGMT was associated with improved overall survival. These results also suggest that mMGMT is predictive, as patients treated with adjuvant chemoradiation or adjuvant radiation therapy did have improved overall survival with mMGMT, though there was no difference in overall survival observes amongst patients receiving adjuvant chemotherapy or those patients receiving no adjuvant treatment. The study also found that only 5% of patients nationwide with Grade 3 Glioma are tested for MGMT. [ABSTRACT FROM AUTHOR]

• Use of chemotherapy is associated with improved overall survival in patients with medulloblastoma. • Extent of resection, timing of chemotherapy, and craniospinal radiation dose do not appear to be associated with overall survival. • Concurrent chemotherapy is not associated with improved overall survival when compared to adjuvant chemotherapy. Adult medulloblastoma is rare, and management is extrapolated from pediatric cases. This investigation evaluated the prognostic role of chemotherapy (and sequencing thereof), the degree of resection, and craniospinal irradiation (CSI) dose. The National Cancer Database was queried for adult (age ≥18) medulloblastoma. Resection was coded as gross (GTR) or subtotal resection (STR) or biopsy only; concurrent chemoradiotherapy (CRT) was defined as receipt within 14 days of each other. Statistics included Kaplan-Meier overall survival (OS) analysis and Cox proportional hazards modeling. Of 1144 patients, 613 had coded surgical information; 242 (39%) did not undergo surgery, 277 (45%) underwent STR, and 94 (15%) had GTR. A total of 428 (37.4%) did not receive chemotherapy, 348 (30.4%) received sequential CRT, and 368 (32.2%) underwent concurrent CRT. Of the 711 patients with CSI dose information, 202 (28.4%) received 23–30 Gy CSI and 509 (71.6%) patients received 30–36 Gy. Median follow-up was 56.5 months. Extent of resection did not correlate with 10-year OS (74.2% biopsy only, 72.7% STR, 82.2% GTR, p > 0.05 all comparisons) or on Cox multivariate analysis. Chemotherapy was associated with higher OS (65.6% vs. 51.2%, p = 0.035) and a trend towards significance on multivariate assessment (p = 0.082). Sequencing of chemotherapy and CSI dose were not associated with OS (p > 0.05 for both). Although causation cannot be implied, neither the extent of resection nor CSI dose associated with OS in adult medulloblastoma. Chemotherapy could have utility in higher-risk patients; concurrent administration may not be beneficial, especially given therapy-induced neuro-cognitive sequelae. [ABSTRACT FROM AUTHOR]

• Multifocal glioblastoma (GBM) is associated with a worse prognosis than unifocal GBM. • MGMT methylation is a favorable prognostic factor for all GBM patients. • Multifocal GBM is associated with a great rate of biopsy only and hypofractionated radiation therapy. Glioblastoma (GBM) presents as a solitary lesion (unifocal), or as multiple discrete lesions (multifocal). Multifocal GBM may have a worse prognosis as compared to unifocal GBM, but existing data are limited to small institutional series. The purpose of the present study was to evaluate demographic and clinical characteristics of patients with unifocal versus multifocal GBM to highlight demographic differences and clinical outcomes for two groups of patients. The National Cancer Database (NCDB) was queried (2004–2016) for patients newly diagnosed with either unifocal or multifocal GBM. Statistics included Kaplan-Meier overall survival (OS) analysis, along with Cox proportional hazards modeling. Of 45,268 total patients, 37,483 (82.8%) had unifocal GBM and 7,785 (17.2%) had multifocal GBM. Patients with unifocal GBM more frequently received gross total resection (GTR) (41.2% versus 25.8%, p < 0.001) and conventionally fractionated radiation therapy (RT) (48.2% versus 42.7%, p < 0.001). Patients with multifocal GBM had a higher rate of surgery with biopsy only (34.0% compared to 24.1%, p < 0.001). Median OS was 12.8 months versus 8.3 months (p < 0.001) for patients with unifocal GBM or multifocal GBM, respectively. On multivariate analysis, factors associated with improved OS included unifocal disease, MGMT methylation, RT use, and chemotherapy use. This is the largest study to date describing outcomes for patients with multifocal GBM, and it shows that multifocal GBM is associated with a decreased use both of GTR and conventionally fractionated RT, as well as worse median OS. Further research is needed to improve clinical outcomes for patients with multifocal GBM. [ABSTRACT FROM AUTHOR]

Breast adenomyoepithelioma (AME) is a rare tumor with the published literature mainly in the form of case reports. Thus, there is currently only limited published data to guide evidence‐based management. We sought to use a large, contemporary US database to evaluate how these patients are managed and describe expected outcomes. The National Cancer Database was queried (2004‐2013) for women with AME. Statistics included multivariable logistic regression, Kaplan–Meier analysis to evaluate overall survival (OS) and Cox proportional hazards modeling. Overall, 110 patients were analyzed. At diagnosis, the median age was 67 years and the median tumor size was 2.0 cm. All but four patients had node‐negative disease. A majority (55%) of tumors were estrogen receptor negative, and only one was positive for HER2/neu. The most common surgical procedure was lumpectomy (60%); a minority (10.9%) of subjects underwent complete axillary nodal dissection, with one‐quarter not undergoing pathologic nodal sampling. Chemotherapy, hormonal therapy, and radiotherapy were utilized in a minority of patients (26%, 8%, and 36%, respectively), and none were associated with OS. At median follow‐up of 52 months, the 5‐year OS for the entire population was 74.4%. Disease‐related characteristics and practice patterns are described for AME, the largest study of this rare tumor to date. Resection is the most important aspect of management, and based on this dataset the low rate of nodal involvement suggests that in some cases nodal sampling could be safely omitted. Adjuvant therapy may be considered on a case‐by‐case basis. Taken together, these data provide valuable insight into a rare neoplasm that may better inform management of these patients. [ABSTRACT FROM AUTHOR]

Metaplastic breast cancer (MBC) is a rare, aggressive variant of breast cancer that has been associated with poor clinical outcomes, as has triple-negative breast (TNBC) cancer. Limited studies compare the clinical characteristics and prognosis of MBC to TNBC. This study uses a large, contemporary US cancer database to compare clinical characteristics and survival outcomes for patients with MBC to those with TNBC. The National Cancer Database was queried for women with cT1-4N1-3M0 MBC or TNBC diagnosed between 2004 and 2013 and treated with definitive surgery. Chi-squared analysis was performed to determine differences between the cohorts. Kaplan-Meier curves compared overall survival (OS), and Cox regression determined patient factors associated with OS. Altogether, 55,847 patients met the inclusion criteria; 50,705 (90.8%) had TNBC and 5,142 (9.2%) had MBC. Most patients had no comorbid conditions (82%), N0 disease (71%), poorly differentiated histology (77%), received chemotherapy (87%), and received radiation therapy (60%). Amongst all patients, patients with TNBC disease were observed to have greater OS than those with MBC (5-year OS 72.0% vs 55.8%, p < 0.001). The greater observed OS for patients with TNBC persisted when controlling for stage and when comparing propensity score matched cohorts. On Cox regression, lower age, T1 status, N0 status, chemotherapy, TNBC disease, and radiation therapy (RT) were associated with improved OS. MBC had an association with poorer OS compared to TNBC, while RT and chemotherapy receipt were associated with improved OS for patients regardless of stage. Further studies are needed to corroborate the conclusions herein. • Metaplastic breast cancer is associated with poor clinical outcomes. • Metaplastic breast cancer associated with worse survival than patients with triple negative invasive ductal carcinoma. • Radiation therapy and chemotherapy associated with improved survival for patients with metaplastic breast cancer. [ABSTRACT FROM AUTHOR]

Background: Although randomized data support omitting adjuvant radiotherapy (RT) following breast conservation for T1‐2N0 estrogen receptor positive breast cancer in ≥70‐year‐old women, there remains a knowledge gap regarding its omission for triple‐negative BC (TNBC). Methods and materials: The National Cancer Database (NCDB) was queried for ≥70‐year‐old females with newly diagnosed T1‐2N0M0 TNBC treated with breast conservation. Multivariable logistic regression ascertained factors associated with adjuvant RT administration. Overall survival (OS) between patients treated with or without adjuvant RT was estimated using the Kaplan‐Meier method. Cox proportional hazards modeling determined variables associated with OS. Results: Of 8526 patients, 6283 (74%) patients received adjuvant RT, and 2243 (26%) did not. RT was more frequently withheld in older patients, those with higher comorbidities, lower income, pT2 disease, following margin‐positive resection, receipt of chemotherapy, and at academic centers (P < 0.05 for all). Median follow‐up was 38.0 months. Five‐year OS was greater in the adjuvant RT group (77.2% vs 55.3%, P < 0.001); these differences persisted when stratifying for age, T stage, and chemotherapy utilization (P < 0.001 for all). Omission of RT was also independently associated with poorer OS on multivariate analysis (P < 0.001). Conclusions: This investigation, the largest known such study to date, observed that omission of adjuvant RT for elderly women with T1‐2N0 TNBC was associated with poorer OS; this was observed across a range of age groups, as well as following stratification by T stage and chemotherapy usage. Although these results do not imply causation, caution must be exercised when considering omission of adjuvant RT in node‐negative TNBC patients. [ABSTRACT FROM AUTHOR]

Abstract Purpose Pleomorphic lobular carcinoma (PLC) is a rare histologic variant of invasive lobular carcinoma (ILC) that has been associated with worse clinical outcomes than classic ILC. Owing to its rarity, high-volume studies of its clinical characteristics and prognosis are lacking. The purpose of this study was to use a large, contemporary cancer database to investigate the clinical characteristics and survival outcomes for patients with PLC. Methods The National Cancer Database (NCDB) was queried for women with cT1-4N1-3M0 breast cancer with either ILC or PLC histology having received definitive surgical therapy. Chi-squared analysis was performed to determine differences between the cohorts. Kaplan-Meier analysis evaluated overall survival (OS) between all patients and between patients when stratifying by age and subtype. Cox proportional hazards modeling determined variables associated with OS. Results A total of 115,260 patients met the study criteria; of these, 114,859 (99.6%) had ILC, while 401 (0.4%) had PLC. A greater proportion of patients with PLC had T3-4 and node-positive disease, and were more likely to have ER- and HER2+ disease. PLC histology was associated with worse OS on both univariate and multivariate analysis (p < 0.001). PLC was associated with poorer OS in subgroups that were T3-4/N+ (but not T1-2N0) disease and ER+ (but not ER-) cancers, but not by HER2 status. Conclusions Patients with PLC, who were more likely to have ER- and HER2+ disease, experienced worse OS than patients with ILC, which may be limited to patients with more advanced clinical stage and ER + disease. Further work is needed to determine the optimal treatment for this more aggressive form of breast cancer. Highlights • Patients with pleomorphic lobular cancer (PLC) more likely to have aggressive disease. • PLC patients more likely to be node positive and have T3-4 disease. • PLC patients had worse overall survival than invasive lobular patients. [ABSTRACT FROM AUTHOR]

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 ongoing randomized studies are assessing the impact of omission of chemotherapy (CT) in low-risk node-positive Luminal A breast. The goal of this investigation was to evaluate trends and practice patterns of adjuvant CT use in Luminal A pT1-3N1 breast cancer, along with determining the clinical benefit from adjuvant CT in this patient population. Methods The National Cancer Data Base was queried (2004–2014) for women with pT1-3N1 luminal A invasive ductal carcinoma receiving adjuvant hormonal therapy (HT). Multivariable logistic regression ascertained factors associated with adjuvant CT administration. Kaplan-Meier analysis evaluated overall survival (OS) between patients treated with CT/HT vs. HT alone, while sub-stratifying patients by age. Results Of 8548 total patients, 5182 (61%) received CT/HT, while 3366 (39%) received HT alone. A steady rise in omission of adjuvant CT was observed, from 14% (2004–2005) to 41% (2012–2014). A decision not to use CT was more likely in more recent time periods, in older patients, at academic centers, following lumpectomy, and with lower T classification (p < 0.05 for all). CT was associated with higher OS in all patients (p < 0.001) and women ≤50 years old (p = 0.030), but not for ages 51–60 (p = 0.116), 61–70 (p = 0.222), or >70 (p = 0.239). Conclusions Using CT for Luminal A N1 breast cancer is decreasing over time, primarily in older patients and at academic centers. Although CT is still associated with an OS advantage in all patients, subgroup analysis demonstrated no OS benefit in women >50 years of age. These results have implications on the ongoing randomized trials. [ABSTRACT FROM AUTHOR]

Aim: This study evaluated national practice patterns of cT1N0M0 renal cell cancer, with a focus on stereotactic body radiation therapy (SBRT) utilization. Methods: The National Cancer Database was queried (2004-2013) for patients with newly-diagnosed cT1a/bN0M0 renal cell cancer that received definitive treatment. Temporal trends in utilization were tabulated. Results: Altogether, 138,495 patients met inclusion criteria; 13,725 (9.9%) patients received ablative therapy, 57,924 (41.8%) partial nephrectomy, 67,168 (48.5%) radical nephrectomy and 308 (0.2%) external beam radiation therapy (EBRT). The proportion of EBRT that was SBRT increased substantially from 25% in 2004 to 95.4% in 2013, with a sharp inflection point from 2005 to 2006. Conclusion: SBRT utilization has sharply risen over time; in most recent years, the vast majority of EBRT is delivered in the form of SBRT. [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]

This study evaluated practice patterns, outcomes, and predictors of survival with respect to the addition of chemotherapy to definitive hypofractionated radiation therapy (HFRT) for glioblastoma in a general patient population. The National Cancer Data Base was queried for patients diagnosed with glioblastoma between 2005 and 2012 that received definitive HFRT with or without chemotherapy. Patient, tumor, and treatment parameters were extracted. Statistics included Kaplan-Meier analysis to evaluate overall survival (OS) as well as Cox proportional hazards modeling to determine variables associated with receipt of chemotherapy and OS. Propensity score matching was performed in order to assess groups in a balanced manner while reducing indication biases. 693 patients met the inclusion criteria, of which 297 (42.9%) received HFRT alone, while 396 (57.1%) received chemotherapy and radiation therapy. Median follow-up was 5.2 months. Factors independently associated with chemotherapy delivery included age ≤ 65, methylated MGMT, and Asian race. Chemotherapy use was associated with improved median OS (6.8 vs. 4.3 months, p < 0.001). This persisted in both age groups of age ≤ 65 (8 vs. 4.4 months, p < 0.001) and > 65 years (6.1 vs. 4.3 months, p = 0.002) as well as on propensity-matched analysis (6.0 vs. 4.3 months, p < 0.001). In this patient population, novel independent predictors of OS were identified, which included the addition of chemotherapy (p < 0.001), receipt of surgery other than biopsy (both p < 0.05), and treatment at an academic institution (p = 0.002). Addition of chemotherapy to definitive HFRT was associated with improved OS in patients ≤ 65 and > 65 years of age. Chemotherapy was an independent predictor of OS, along with receipt of surgery and treatment at an academic institution. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) is traditionally considered to be radioresistant; therefore, conventional radiotherapy (RT) fraction sizes of 1.8 to 2 Gy are thought to have little role in the management of primary RCC, especially for curative disease. In the setting of metastatic RCC, conventionally fractionated RT has been an effective palliative treatment in 50% of patients. Recent technological advances in radiation oncology have led to the clinical implementation of image-guided radiotherapy, allowing biologically potent doses to the tumors intra- and extra-cranially. As predicted by radiobiologic modeling, favorable outcomes have been observed with highly hypofractionated schemes modeled after the experience with intracranial stereotactic radiosurgery (SRS) for RCC brain metastases with reported local control rates averaging 85%. At present, both primary and metastatic RCC tumors may be successfully treated using stereotactic approaches, which utilize steep dose gradients to maximally preserve function and avoid toxicity of adjacent organs including liver, uninvolved kidney, bowel, and spinal cord regions. Future endeavors will combine stereotactic body radiation therapy (SBRT) with novel targeted therapies, such as tyrosine kinase inhibitors and targeted rapamycin (mTOR) inhibitors, to maximize both local and systemic control. [ABSTRACT FROM AUTHOR]

The standard treatment for metastatic cancer is systemic therapy. However, in a subset of patients with limited extracranial metastases or oligometastases, local ablative therapy in combination with systemic therapy may improve treatment outcomes. Stereotactic body radiation therapy (SBRT) has emerged as a novel approach for local ablation of extracranial oligometastases. There is a good body of experience in the use of SBRT for the treatment of oligometastases in various sites including the lung, the liver and the spine with promising results. This article provides an overview of the use of SBRT in the management of extracranial oligometastases. [ABSTRACT FROM AUTHOR]

: PurposeThe intensity-modulated radiation therapy (IMRT) treatment planning system generates tightly constricted isodose lines. It is very important to define the margins that are acceptable in the treatment of prostate cancer to maximize the dose escalation and normal tissue avoidance advantages offered by IMRT. It is necessary to take into account subclinical disease and the potential for extracapsular spread. Organ and patient motion as well as setup errors are variables that must be minimized and defined to avoid underdosing the tumor or overdosing the normal tissues. We have addressed these issues previously. The purpose of the study was twofold: to quantify the radial distance of extracapsular extension in the prostatectomy specimens, and to quantify differences between the pathologic prostate volume (PPV), CT-based gross tumor volume (GTV), and planning target volume (PTV).: Methods and materialsTwo related studies were undertaken. A total of 712 patients underwent prostatectomy between August 1983 and September 1995. Pathologic assessment of the radial distance of extracapsular extension was performed. Shrinkage associated with fixation was accounted for with a linear shrinkage factor. Ten patients had preoperative staging studies including a CT scan of the pelvis. The GTV was outlined and volume determined from these CT scans. The PTV, defined as GTV with a 5-mm margin in all dimensions, was then calculated. The Peacock inverse planning system (NOMOS Corp., Sewickley, PA) was used. The PPV, GTV, and PTV were compared for differences and evaluated for correlation.: ResultsExtracapsular extension (ECE) (i.e., prostatic capsular invasion level 3 [both focal and established]) was found in 299 of 712 patients (42.0%). Measurable disease extending radially outside the prostatic capsule (i.e., ECE level 3 established) was noted in 185 of 712 (26.0%). The median radial extension was 2.0 mm (range 0.50–12.00 mm) outside the prostatic capsule. As a group, 20 of 712 (2.8%) had extracapsular extension of more than 5 mm. In the volumetric comparison and correlation study of the GTV and PTV to the PPV, the average GTV was 2 times larger than the PPV. The average PTV was 4.1 times larger than the PPV.: ConclusionsThis is the largest series in the literature quantitatively assessing prostatic capsular invasion (i.e., the radial extracapsular extension). It is the first report of a comparison of PPV to CT-planned GTV and PTV. Using patient and prostate immobilization, 5 mm of margin to the GTV in this study provided sufficient coverage of the tumor volume based on data gathered from 712 patients. In the absence of prostate immobilization, additional margins of differing amounts depending on the technique employed would have to be placed to account for target, patient, and setup uncertainties. The large mean difference between CT-based estimates of the tumor volume and target volume (GTV+PTV) and PPV added further evidence for adequacy of tumor coverage. Target immobilization, setup error, and coverage of subclinical disease must be addressed carefully before successful implementation of IMRT to maximize its ability to escalate dose and to spare normal tissue simultaneously and safely. [Copyright &y& Elsevier]

: PurposeTo evaluate the predictors of xerostomia in the treatment of head-and-neck cancers treated with intensity-modulated radiation therapy (IMRT), using the simultaneous modulated accelerated radiation therapy (SMART) boost technique. Dosimetric parameters of the parotid glands are correlated to subjective salivary gland function.: Methods and materialsBetween January 1996 and June 2000, 30 patients with at least 6 months follow-up were evaluated for subjective xerostomia after being treated definitively for head-and-neck cancer with the SMART boost technique. Threshold limits for the ipsilateral and contralateral parotid glands were 35 Gy and 25 Gy, respectively. Dosimetric parameters to the parotid glands were evaluated. The median follow-up time was 38.5 months (mean 39.9 months). The results of the dosimetric parameters and questionnaire were statistically correlated.: ResultsXerostomia was assessed with a 10-question subjective salivary gland function questionnaire. The salivary gland function questionnaire (questions 1, 2, 3, 4, 6, and 9) correlated significantly with the dosimetric parameters (mean and maximum doses and volume and percent above tolerance) of the parotid glands. These questions related to overall comfort, eating, and abnormal taste. Questions related to thirst, difficulty with speech or sleep, and the need to carry water daily did not correlate statistically with the dosimetric parameters of the parotid glands.: ConclusionsQuestions regarding overall comfort, eating, and abnormal taste correlated significantly with the dosimetric parameters of the parotid glands. Questions related to thirst, difficulty with speech or sleep, and the need to carry water daily did not correlate statistically with the dosimetric parameters of the parotid glands. Dosimetric sparing of the parotid glands improved subjective xerostomia. IMRT in the treatment of head-and-neck cancer can be exploited to preserve the parotid glands and decrease xerostomia. This is feasible even with an accelerated treatment regimen like the SMART boost. More patients need to be evaluated using IMRT to identify relevant dosimetric parameters. [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]

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 In 2009, the American Society for Radiation Oncology (ASTRO) published consensus recommendations that stated ductal carcinoma in situ (DCIS) patients were in a “cautionary” group for accelerated partial breast irradiation (APBI) and should not receive APBI outside of a clinical trial. However, very recently, ASTRO placed low-risk DCIS patients in the “suitable” category. Given this recent change, we aimed to use the Surveillance, Epidemiology, and End Results (SEER) database to evaluate past patterns of implantable APBI (IAPBI) utilization in women with DCIS. Methods and Materials The Surveillance, Epidemiology, and End Results database was queried for patients from 2000 to 2012 with DCIS that underwent lumpectomy and adjuvant radiation therapy. Patients receiving IAPBI were differentiated from those receiving whole breast radiation therapy. Trends based on treatment year and patient demographics were collected, and multivariable logistic regression determined factors independently predictive of use of IAPBI. Results Of 52,012 eligible patients, 49,450 (95%) underwent external beam radiation and 2562 (5%) received APBI. Though IAPBI utilization steadily increased from 2000 (0.2% of the study population) to 2008 (9.4%), it abruptly declined in 2009 (7.9%, p = 0.009) and yearly thereafter. The 40–49 age group was proportionally most associated with this decline (8.6% in 2008 to 4.3% in 2009). Factors independently associated with IAPBI receipt included increasing age, hormone receptor negative status, and women living in the South. Conclusions Patterns of IAPBI administration in DCIS are described. These trends are important to consider as a benchmark going forward, in light of the very recent change in ASTRO recommendations to include low-risk DCIS patients. [ABSTRACT FROM AUTHOR]

Purpose The standard treatment for stage IB1 and IIA1 cervical carcinoma is surgery. For non-operative cases, the National Comprehensive Cancer Network recommends definitive radiotherapy (RT) with or without chemotherapy. This study sought to determine whether the addition of chemotherapy to RT improved overall survival (OS) for patients with stage IB1 and IIA1 cervical cancer. Methods We used the National Cancer Data Base to identify patients with stage IB1 or stage IIA1 cervical cancer diagnosed in 2004 to 2012 who received definitive RT with or without chemotherapy. Patient, tumor, and treatment facility characteristics were assessed. Kaplan-Meier analysis was performed to compare overall survival (OS) between groups. Cox regression analysis was performed to identify factors associated with survival. Propensity-score matching was used to compare survival outcomes while accounting for indication bias. Results 825 patients met the specified criteria. 275 (33.3%) of patients received treatment with RT alone, whereas 550 (66.7%) were treated with CRT. The median OS in patients treated with RT alone was 121.1 months, while the median OS for patients treated with CRT was not reached (hazard ratio [HR] = 0.719; 95% confidence interval [CI] 0.549–0.945). Propensity-score matched analysis confirmed that CRT was superior to RT alone (HR = 0.701; 95% CI 0.509 to 0.963). Conclusions Our study suggests the addition of chemotherapy to definitive RT in patients with stage IB1 or stage IIA1 cervical cancer is associated with an improvement in OS. Prospective studies are recommended to validate these results and to further investigate the quality of life differences associated with chemotherapy use. [ABSTRACT FROM AUTHOR]

Abstract: 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 &y& Elsevier]