The radiopharmaceutical radium-223 has immunomodulatory effects in patients and facilitates anti-programmed death receptor-1 therapy in murine models of bone metastatic prostate cancer.

BACKGROUND & PURPOSE: Radium-223 (Ra223) improves survival in metastatic prostate cancer (mPC), but its impact on systemic immunity is unclear, and biomarkers of response are lacking. We examined markers of immunomodulatory activity during standard clinical Ra223 and studied the impact of Ra223 on response to immune checkpoint inhibition (ICI) in preclinical models. MATERIALS & METHODS: We conducted a single-arm biomarker study of Ra223 in 22 bone mPC patients. We measured circulating immune cell subsets and a panel of cytokines before and during Ra223 therapy and correlated them with overall survival (OS). Using two murine mPC models-orthotopic PtenSmad4-null and TRAMP-C1 grafts in syngeneic immunocompetent mice-we tested the efficacy of combining Ra223 with ICI. RESULTS: Above-median level of IL-6 at baseline was associated with a median OS of 358 versus 947 days for below levels; p = 0.044, from the log-rank test. Baseline PlGF and PSA inversely correlated with OS (p = 0.018 and p = 0.037, respectively, from the Cox model). Ra223 treatment was associated with a mild decrease in some peripheral immune cell populations and a shift in the proportion of MDSCs from granulocytic to myeloid. In mice, Ra223 increased the proliferation of CD8+ and CD4+ helper T cells without leading to CD8+ T cell exhaustion in the mPC lesions. In one of the models, combining Ra223 and anti-PD-1 antibody significantly prolonged survival, which correlated with increased CD8+ T cell infiltration in tumor tissue. CONCLUSION: The inflammatory cytokine IL-6 and the angiogenic biomarker PlGF at baseline were promising outcome biomarkers after standard Ra223 treatment. In mouse models, Ra223 increased intratumoral CD8+ T cell infiltration and proliferation and could improve OS when combined with anti-PD-1 ICI.

Disparities in testicular cancer incidence, mortality, and place of death trends from 1999 to 2020: A comprehensive cohort study.

BACKGROUND: Testicular cancer (TC) mortality rates have decreased over time, however it is unclear whether these improvements are consistent across all communities. AIMS: The aim of this study was to analyze trends in TC incidence, mortality, and place of death (PoD) in the United States between 1999-2020 and identify disparities across race, ethnicity, and geographic location. METHODS AND RESULTS: This cross-sectional study used CDC WONDER and NAACCR, to calculate age-adjusted rates of TC incidence and mortality, respectively. PoD data for individuals who died of TC were collected from CDC WONDER. Using Joinpoint analysis, longitudinal mortality trends were evaluated by age, race, ethnicity, US census region, and urbanization category. TC stage (localized vs metastatic) trends were also evaluated. Univariate and multivariate regression analysis identified demographic disparities for PoD. A total of 8,456 patients died of TC from 1999-2020. Average annual percent change (AAPC) of testicular cancer-specific mortality (TCSM) remained largely stable (AAPC, 0.4; 95% CI -0.2 to 0.9; p = 0.215). Men ages 25-29 experienced a significant increase in TCSM (AAPC, 1.3, p = 0.003), consistent with increased metastatic testicular cancer-specific incidence (TCSI) trend for this age group (AAPC, 1.6; p < 0.01). Mortality increased for Hispanic men (AAPC, 1.7, p < 0.001), with increased metastatic TCSI (AAPC, 2.5; p < 0.001). Finally, younger (<45), single, and Hispanic or Black men were more likely to die in medical facilities (all p < 0.001). The retrospective study design is a limitation. CONCLUSION: Significant increases in metastatic TC were found for Hispanic men and men aged 25-29 potentially driving increasing testicular cancer specific mortality in these groups. Evidence of racial and ethnic differences in place of death may also highlight treatment disparities.

Longitudinal Analysis of Bladder Cancer-Specific Mortality Trends in the United States.

BACKGROUND: Bladder cancer is the tenth leading cause of cancer death in the United States (US). Advances in diagnosis, imaging, and treatments have led to improvements in bladder cancer management. OBJECTIVE: To evaluate longitudinal bladder cancer mortality trends from 1999-2020 in the US by gender, race, ethnicity, age, geographic region, and urbanization category. METHODS: Age-adjusted bladder cancer death and incidence rates of individuals in the US of all ages between 1999-2020 were obtained using the CDC WONDER and NAACCR databases. Trends and average annual percent changes (AAPC) in age-adjusted Bladder Cancer-Specific Mortality (BCSM) and incidence rates were estimated. Data were analyzed from May 2023 to October 2023. RESULTS: From 1999-2020, overall BCSM decreased by 0.4% annually, with a dramatic decrease in deaths between 2015-2020 (AAPC: -2.0% [95% CI: -2.6,-1.3]). However, BCSM rates and metastatic malignant bladder cancer incidence rates from 1999-2020 increased for individuals≥85 years old (AAPC for BCSM: 0.8% [95% CI:0.5,1.1]; AAPC for metastatic malignant incidence: 2.5% [95% CI: 2.0,2.9]). Increases in BCSM were found for certain years in the South, in rural areas, and for Non-Hispanic White and Asian or Pacific Islander individuals. CONCLUSIONS: Overall mortality from bladder cancer has been decreasing in the US over two decades. Upon disaggregation, increasing trends were found for BCSM and for metastatic malignant bladder cancer incidence for individuals≥85 years old from 1999-2020. Further evaluation of these trends is essential to understand how to target specific populations to improve patient outcomes.

Low-dose preoperative radiation, resection, and reduced-field postoperative radiation for soft tissue sarcomas.

BACKGROUND AND OBJECTIVES: Radiotherapy (RT) enables conservative surgery for soft tissue sarcoma (STS). RT can be delivered either pre-operatively (PreRT) or postoperatively (PORT), yet in some patients, neither approach is fully satisfactory (e.g., urgent surgery or wound healing risk prevents PreRT, yet PORT alone cannot cover the entire surgical field). We hypothesized that, in such situations, low-dose PreRT (LD-PreRT) would decrease the risk of intraoperative tumor seeding and thus permit PORT to a reduced volume (covering the high-risk tumor bed but not all surgically manipulated tissues). METHODS: We identified a single-institution retrospective cohort of 78 patients treated with LD-PreRT (10-30 Gy), resection, and PORT between 1980 and 2018. RESULTS: At a median follow-up of 8.2 years, 8-year overall survival (OS) was 65.9%, disease-free survival (DFS) 50.5%, and local control (LC) 76.7%; in 45 patients with extremity/superficial trunk (E/ST) STS, 8-year LC was 80.9%. Both before and after propensity score adjustment, there were no differences in OS, DFS, or LC between this cohort and a separate cohort of 394 STS (221 E/ST-STS) patients treated with surgery and PORT alone. CONCLUSIONS: In patients for whom neither PreRT nor PORT alone is optimal, LD-PreRT may prevent intraoperative tumor seeding and enable PORT to a reduced volume while preserving oncologic outcomes.

Brain-Specific Relative Biological Effectiveness of Protons Based on Long-term Outcome of Patients With Nasopharyngeal Carcinoma.

PURPOSE: Uncertainties in relative biological effectiveness (RBE) constitute a major pitfall of the use of protons in clinics. An RBE value of 1.1, which is based on cell culture and animal models, is currently used in clinical proton planning. The purpose of this study was to determine RBE for temporal lobe radiographic changes using long-term follow-up data from patients with nasopharyngeal carcinoma. METHODS AND MATERIALS: Five hundred sixty-six patients with newly diagnosed nasopharyngeal carcinoma received double-scattering proton therapy or intensity modulated radiation therapy at our institutions. The 2 treatment cohorts were well matched. Proton dose distributions were simulated using Monte Carlo and compared with those obtained from the proton clinical treatment planning system. Late treatment effect was defined as development of enhancement of temporal lobe on T1-weighted magnetic resonance imaging, with or without accompanying clinical symptoms. The tolerance dose was calculated with receiving operator characteristic analysis and the Youden index. Tolerance curves, expressed as a cumulative dose-volume histogram, were generated using the cutoff points. RESULTS: With a median follow-up period >5 years for both cohorts, 10% of proton patients and 4% of patients undergoing intensity modulated radiation therapy developed temporal lobe enhancement in unilateral temporal lobe. There was no significant difference in dose distributions between the Monte Carlo method and treatment planning system. The tolerance dose-volume levels were V10 (26.1%), V20 (21.9%), V30 (14.0%), V40 (7.7%), V50 (4.8%), and V60 (3.3%) for proton therapy (P < .03). Comparison of the two tolerance curves revealed that tolerance doses of proton treatments were lower than that of photon treatments at all dose levels. The dose tolerance at D1% was 58.56 Gy for protons and 69.07 Gy for photons. The RBE for temporal lobe enhancement from proton treatments were calculated to be 1.18. CONCLUSIONS: Using long-term clinical outcome of patients with nasopharyngeal carcinoma, our data suggest that the RBE for temporal lobe enhancement is 1.18 at D1%. A prospective study in a large cohort would be necessary to confirm these findings.

Lifestyle Counseling and Long-term Clinical Outcomes in Patients With Diabetes.

OBJECTIVE: To investigate the relationship between lifestyle counseling in primary care settings and clinical outcomes in patients with diabetes. RESEARCH DESIGN AND METHODS: We retrospectively studied hyperglycemic adults with diabetes treated at primary care practices between 2000 and 2014. We analyzed the relationship between frequency of lifestyle counseling (identified using natural language processing of electronic notes) and a composite outcome of death and cardiovascular events during subsequent follow-up. RESULTS: Among patients with monthly counseling or more, 10-year cumulative incidence of the primary outcome was 33.0% compared with 38.1% for less than monthly counseling (P = 0.0005). In multivariable analysis, higher frequency of lifestyle counseling was associated with lower incidence of the primary outcome (hazard ratio 0.88 [95% CI 0.82-0.94]; P < 0.001). CONCLUSIONS: More frequent lifestyle counseling was associated with a lower incidence of cardiovascular events and death among patients with diabetes.

Individualization of Clinical Target Volume Delineation Based on Stepwise Spread of Nasopharyngeal Carcinoma: Outcome of More Than a Decade of Clinical Experience.

PURPOSE: Radiation-related toxicity in nasopharyngeal carcinoma (NPC) is common. There are no well-established guidelines for clinical target volume (CTV) delineation with long-term follow-up. Current consensus continues to rely heavily on bony landmarks and fixed margins around the gross tumor volume (GTV), an approach used to define fields in the conventional 2- and 3-dimensional radiation therapy era. METHODS AND MATERIALS: We retrospectively evaluated patients with newly diagnosed nonmetastatic NPC treated with definitive radiation therapy using a technique of CTV delineation based on individual tumor extent and the orderly stepwise pattern of tumor spread. Dosimetric comparisons were made between national protocol HN001 and our contouring strategies on a representative early- and advanced-stage NPC. The primary endpoints were patterns of failure and local control; secondary endpoints included regional control and survival, estimated using the Kaplan-Meier method. RESULTS: Between 1999 and 2013, 73 patients (88% with stage 3-4 disease) were treated with median follow-up of 90 months for surviving patients. Median dose to GTV was 70 Gy. Four patients developed local recurrence and 1 patient developed regional recurrence. All locoregional recurrences occurred within the high-dose GTV. The 5-year local control, regional control, and overall survival was 94% (95% confidence interval [CI], 85%-98%), 99% (95% CI, 90%-100%), and 84% (95% CI, 73%-91%), respectively. Compared with HN001, our contouring strategy resulted in 62% and 36% reduction in CTV for T1 and T4 disease, respectively. In the T1 tumor, the reduction of doses to the contralateral parotid, optic nerve, and cochlea were 54%, 50%, 34% respectively. In the T4 case, there was a decrease of optic chiasm dose of 46% and contralateral optic nerve of 37%. There were 10 grade 3 toxicities. There was no grade 2 or higher xerostomia and no grade 4/5 toxicity. CONCLUSIONS: Our long-term experience with individualized CTV delineation based on stepwise patterns of spread results in excellent local control, with no recurrence outside the GTV.

Quality of life in patients with proton-treated pediatric medulloblastoma: Results of a prospective assessment with 5-year follow-up.

BACKGROUND: To the authors' knowledge, health-related quality of life (HRQOL) outcomes are not well described in patients with medulloblastoma. The use of proton radiotherapy (RT) may translate into an improved HRQOL. In the current study, the authors report long-term HRQOL in patients with proton-treated pediatric medulloblastoma. METHODS: The current study was a prospective cohort HRQOL study of patients with medulloblastoma who were treated with proton RT and enrolled between August 5, 2002, and October 8, 2015. Both child report and parent-proxy report Pediatric Quality of Life Inventory (PedsQL) surveys were collected at baseline during RT and annually thereafter (score range on surveys of 0-100, with higher scores indicating better HRQOL). Patients were dichotomized by clinical/treatment variables and subgroups were compared. Mixed-model analysis was performed to determine the longitudinal trajectory of PedsQL scores. The Student t test was used to compare long-term HRQOL measures with published means from a healthy child population. RESULTS: Survey data were evaluable for 116 patients with a median follow-up of 5 years (range, 1-10.6 years); the median age at the time of diagnosis was 7.6 years (range, 2.1-18.1 years). At baseline, children reported a total core score (TCS) of 65.9, which increased by 1.8 points annually (P<.001); parents reported a TCS of 59.1, which increased by 2.0 points annually. Posterior fossa syndrome adversely affected baseline scores, but these scores significantly improved with time. At the time of last follow-up, children reported a TCS of 76.3, which was 3.3 points lower than that of healthy children (P = .09); parents reported a TCS of 69, which was 11.9 points lower than that of parents of healthy children (P<.001). Increased follow-up time from diagnosis correlated with improved HRQOL scores. CONCLUSIONS: HRQOL scores appear to increase over time after treatment in children treated with proton RT for medulloblastoma but remain lower compared with those of parent-proxy reports as well as published means from a healthy normative sample of children. Additional follow-up may translate into continued improvements in HRQOL. Cancer 2018. © 2018 American Cancer Society.

Long-Term Outcomes After Proton Beam Therapy for Sinonasal Squamous Cell Carcinoma.

PURPOSE: Squamous cell carcinoma (SCC) is the most common sinonasal cancer and is associated with one of the poor outcomes. Proton therapy allows excellent target coverage with maximal sparing of adjacent normal tissues. We evaluated the long-term outcomes in patients with sinonasal SCC treated with proton therapy. METHODS AND MATERIALS: Between 1991 and 2008, 54 patients with Stage III and IV SCC of the nasal cavity and paranasal sinus received proton beam therapy at our institution to a median dose of 72.8 Gy(RBE). Sixty-nine percent underwent prior surgical resection, and 74% received elective nodal radiation. Locoregional control and survival probabilities were estimated with the Kaplan-Meier method. Multivariate analyses were performed using the Cox proportional-hazards model. Treatment toxicity was scored using the Common Terminology Criteria for Adverse Events version 4.0. RESULTS: With a median follow-up time of 82 months in surviving patients, there were 10 local, 7 regional, and 11 distant failures. The 2-year and 5-year actuarial local control rate was 80%. The 2-year and 5-year rates of overall survival were 67% and 47%, respectively. Only smoking status was predictive for worse locoregional control, with current smokers having a 5-year rate of 23% compared with 83% for noncurrent smokers (P=.004). Karnofsky performance status ≤80 was the most significant factor predictive for worse overall survival in multivariate analysis (adjusted hazard ratio 4.5, 95% confidence interval 1.6-12.5, P=.004). There were nine grade 3 and six grade 4 toxicities, and no grade 5 toxicity. Wound adverse events constituted the most common grade 3-4 toxicity. CONCLUSIONS: Our long-term results show that proton radiation therapy is well tolerated and yields good locoregional control for SCC of the nasal cavity and paranasal sinus. Current smokers and patients with poor performance status had inferior outcomes. Prospective study is necessary to compare IMRT with proton therapy in the treatment of sinonasal malignancy.

Body mass index and all-cause mortality in patients with hypertension.

OBJECTIVE: To characterize the relationship between body mass index (BMI) and all-cause mortality among adults with hypertension. METHODS: We conducted a retrospective cohort study of adults with hypertension from The Health Improvement Network primary care research database in the United Kingdom. Mortality rates within each BMI category were compared after adjustment for age, sex, pre existing medical conditions, smoking, alcohol use, and socioeconomic status. RESULTS: During a median follow-up period of 8.0 years, 34,354 deaths occurred (8.8%) among the 388,724 study patients. In multivariable analysis that included interaction terms between smoking, heavy alcohol use, preexisting cardiovascular disease and chronic obstructive pulmonary disease (COPD), and BMI category to account for these conditions' association with increased mortality at lower BMI levels, a U-shaped relationship was observed between BMI and mortality, with no difference in mortality in overweight (25.0-29.9 kg/m(2) ) versus normal (18.5-24.9 kg/m(2) ) BMI (risk ratio 1.00, 95% confidence interval 0.95 to 1.04, P = 0.80). In multivariable analysis that used narrower BMI categories, lowest mortality was observed between BMI of 23.0 and 26.9 kg/m(2) . CONCLUSIONS: Patients with hypertension who have no history of smoking, heavy alcohol use, cardiovascular disease, or COPD have lowest mortality between BMI of 23.0 and 26.9 kg/m(2) .

Electronic Documentation of Lifestyle Counseling and Glycemic Control in Patients With Diabetes.

OBJECTIVE: To establish quantitative characteristics of lifestyle counseling documentation associated with improved glycemic control in patients with diabetes. RESEARCH DESIGN AND METHODS: We retrospectively studied 10,870 hyperglycemic (HbA1c ≥7.0% [53 mmol/mol]) adults with diabetes followed at primary care practices affiliated with two academic hospitals between 2000 and 2010. Documentation intensity was represented by the mean number of characters per note documenting lifestyle counseling. Heterogeneity was calculated as the normalized Levenshtein distance between lifestyle counseling sentences between consecutive notes. Cox proportional hazards model was constructed to assess association of heterogeneity and intensity of lifestyle counseling documentation to time to HbA1c <7.0% (53 mmol/mol) while adjusting for demographics, initial HbA1c level, insulin therapy, medication intensification, and frequency of lifestyle counseling. RESULTS: Comparing patients in the highest versus lowest tertile by documentation heterogeneity and documentation intensity, median time to HbA1c <7.0% (53 mmol/mol) was 26 vs. 39 months and 24 vs. 39 months, respectively (P < 0.001 for all). In multivariable analysis, an increase of documentation heterogeneity by 0.15 units and an increase of documentation intensity by 45 characters/note was associated with hazard ratios of 1.08 (95% CI 1.04-1.12; P < 0.001) and 1.27 (95% CI 1.23-1.31; P < 0.001) for time to HbA1c target, respectively. CONCLUSIONS: Higher heterogeneity and intensity of lifestyle counseling documentation in provider notes were associated with better glycemic control. Further studies involving direct observation of patient care are needed to establish the nature of the relationship between documentation characteristics and patient outcomes.

Optimal systolic blood pressure target, time to intensification, and time to follow-up in treatment of hypertension: population based retrospective cohort study.

OBJECTIVES: To investigate the optimal systolic blood pressure goal above which new antihypertensive medications should be added or doses of existing medications increased ("systolic intensification threshold") and to determine the relation between delays in medication intensification and follow-up and the risk of cardiovascular events or death. DESIGN: Retrospective cohort study. SETTING: Primary care practices in the United Kingdom, 1986-2010. PARTICIPANTS: 88 756 adults with hypertension from The Health Improvement Network nationwide primary care research database. MAIN OUTCOME MEASURES: Rates of acute cardiovascular events or death from any cause for patients with different hypertension treatment strategies (defined by systolic intensification threshold, time to intensification, and time to follow-up over the course of a 10 year treatment strategy assessment period) after adjustment for age, sex, smoking status, socioeconomic deprivation, history of diabetes, cardiovascular disease or chronic kidney disease, Charlson comorbidity index, body mass index, medication possession ratio, and baseline blood pressure. RESULTS: During a median follow-up of 37.4 months after the treatment strategy assessment period, 9985 (11.3%) participants had an acute cardiovascular event or died. No difference in risk of the outcome was seen between systolic intensification thresholds of 130-150 mm Hg, whereas systolic intensification thresholds greater than 150 mm Hg were associated with progressively greater risk (hazard ratio 1.21, 95% confidence interval 1.13 to 1.30; P<0.001 for intensification threshold of 160 mm Hg). Outcome risk increased progressively from the lowest (0-1.4 months) to the highest fifth of time to medication intensification (hazard ratio 1.12, 1.05 to 1.20; P=0.009 for intensification between 1.4 and 4.7 months after detection of elevated blood pressure). The highest fifth of time to follow-up (>2.7 months) was also associated with increased outcome risk (hazard ratio 1.18, 1.11 to 1.25; P<0.001). CONCLUSIONS: Systolic intensification thresholds higher than 150 mm Hg, delays of greater than 1.4 months before medication intensification after systolic blood pressure elevation, and delays of greater than 2.7 months before blood pressure follow-up after antihypertensive medication intensification were associated with increased risk of an acute cardiovascular event or death. These findings support the importance of timely medical management and follow-up in the treatment of patients with hypertension.

Role of post-operative radiation boost for soft tissue sarcomas with positive margins following pre-operative radiation and surgery.

BACKGROUND AND OBJECTIVES: The role of a radiation therapy (RT) boost for positive margins following pre-operative RT and surgery in extremity soft tissue sarcomas (STS) is unclear. We assessed the contribution of a boost to local control (LC), disease-free survival (DFS), and overall survival (OS). METHODS: We identified 67 patients treated from 1987 to 2011 with pre-operative RT and surgery with positive margin(s). Select patients received a boost delivered as peri-operative Iridium-192 brachytherapy (BRT), intra-operative electrons (IORT), or post-operative external beam RT (EBRT). RESULTS: Ten patients received no RT boost, 10 received a BRT or IORT boost, and 47 received an EBRT boost. Five-year LC rates for no boost, BRT/IORT boost, and EBRT boost were 100%, 78%, and 71% (P = 0.5). On multivariate analysis, there were no significant predictors for LC. Variables associated with improved DFS rates were single positive margin (P = 0.007) and low tumor grade (P = 0.03). Tumor size <5 cm (P = 0.003), low grade (P = 0.001), and boost (P = 0.02) were associated with longer survival. CONCLUSIONS: We did not identify a LC advantage for an RT boost. Given the unidentified selection factors for delivery of boost and its potential toxicities, its role in this setting remains unproven.

Clinical outcome of isolated locoregional recurrence in patients with breast cancer according to their primary local treatment.

INTRODUCTION: This study assessed the clinical outcome and prognostic factors in patients with breast cancer who presented with isolated locoregional recurrence (ILRR) as a first event. MATERIALS AND METHODS: Between 1970 and 2008, 2960 patients with pT1-2, N0-3, M0 primary invasive breast cancer had either breast-conserving therapy (BCT) using lumpectomy and radiation therapy (RT) (group A = 1849 patients) or mastectomy without RT (group B = 1111 patients). Out of groups A and B, 117 and 103 patients, respectively, developed ILRR as a first event. Those 220 patients served as the basis for this study. A multivariate analysis was performed to estimate the clinical outcome of both groups, taking into account clinically relevant variables for the primary tumor and ILRR. RESULTS: The median follow-up after ILRR was 83 months. The median disease-free interval (DFI) was 79 and 38 months for groups A and B, respectively. The overall survival (OS) for group A was 81% and 69% at 5 and 8 years, respectively. For group B, it was 61% and 46%, respectively. The distant metastasis-free survival (DMFS) for group A was 84% at 5 years and remained 84% at 8 years. The DMFS for group B was 60% at 5 years and 52% at 8 years. In multivariate analysis, initial local treatment (BCT vs. mastectomy without RT), pathologic T stage, locoregional recurrence site (local vs. regional), and DFI (≤ 4 years vs. > 4 years) were significant prognostic variables for both OS and DMFS. CONCLUSION: Patients with breast cancer who developed ILRR after BCT as their initial local treatment have better clinical outcome compared with those who had mastectomy without RT.

MRI surveillance following treatment of extremity soft tissue sarcoma.

BACKGROUND AND OBJECTIVES: Local recurrence (LR) following limb-sparing surgery and radiation therapy (RT) for extremity soft tissue sarcoma (STS) is rare. The current study investigates the utility of surveillance nuclear magnetic resonance imaging (MRI) for detection of asymptomatic LRs. METHODS: The study cohort consisted of 168 adult patients with extremity STS treated with limb-sparing surgery and RT with curative intent between October 2001 and January 2011. Follow-up surveillance MRIs and history and physical examinations were performed per the NCCN guidelines with additional MRIs as clinically indicated. The method of LR detection and MRI number and indication were determined. RESULTS: After a median follow-up of 4.7 years (range: 0.6-10.5) 11 (6.5%; 11/168) patients developed LRs. Five hundred two MRIs were obtained, 429 (85.5%; 429/502) for surveillance and 73 (14.5%; 73/502) as clinically indicated. One hundred fourteen patients underwent ≥1 surveillance MRI. The median surveillance MRI interval was 6.4 months (range 1.4-68.9). Surveillance MRI detected an asymptomatic LR in 1 (0.9%; 1/114) patient with a complex reconstruction. CONCLUSIONS: Surveillance MRI infrequently detects asymptomatic LRs following limb-sparing surgery and RT for extremity STS and should be limited to patients whose primary tumor sites are not easily assessed by history and physical examination.

Risk of local failure in breast cancer patients with lobular carcinoma in situ at the final surgical margins: is re-excision necessary?

PURPOSE: To compare the outcome of patients with invasive breast cancer both with and without lobular carcinoma in situ (LCIS)-positive/close surgical margins after breast-conserving treatment. METHODS AND MATERIALS: We retrospectively studied 2358 patients with T1-T2 invasive breast cancer treated with lumpectomy and radiation therapy from January 1980 to December 2009. Median age was 57 years (range, 24-91 years). There were 82 patients (3.5%) with positive/close LCIS margins (<0.2 cm) and 2232 patients (95.7%) with negative margins. A total of 1789 patients (76%) had negative lymph nodes. Patients who received neoadjuvant chemotherapy were excluded. A total of 1783 patients (76%) received adjuvant systemic therapy. Multivariable analysis (MVA) was performed using Cox's proportional hazards model. RESULTS: The 5-year cumulative incidence of locoregional recurrence (LRR) was 3.2% (95% confidence interval [CI] 2.5%-4.1%) for the 2232 patients with LCIS-negative surgical margins (median follow-up 104 months) and 2.8% (95% CI 0.7%-10.8%) for the 82 patients with LCIS-positive/close surgical margins (median follow-up 90 months). This was not statistically significant (P=.5). On MVA, LCIS-positive margins after the final surgery were not associated with increased risk of LRR (hazard ratio [HR] 3.4, 95% CI 0.5-24.5, P=.2). Statistically significant prognostic variables on Cox's MVA for risk of LRR included systemic therapy (HR 0.5, 95% CI 0.33-0.75, P=.001), number of positive lymph nodes (HR 1.11, 95% CI 1.05-1.18, P=.001), menopausal status (HR 0.96, 95% CI 0.95-0.98, P=.001), and histopathologic grade (grade 3 vs grade 1/2) (HR 2.6, 95% CI 1.4-4.7, P=.003). CONCLUSION: Our results suggest that the presence of LCIS at the surgical margin after lumpectomy does not increase the risk of LRR or the final outcome. These findings suggest that re-excision or mastectomy in patients with LCIS-positive/close final surgical margins is unnecessary.

Updated long-term outcomes and prognostic factors for patients with unresectable locally advanced pancreatic cancer treated with intraoperative radiotherapy at the Massachusetts General Hospital, 1978 to 2010.

BACKGROUND: In the current study, the authors evaluated long-term outcomes, intraoperative radiotherapy (IORT)-related toxicity, and prognostic factors for overall survival (OS) among patients with unresectable locally advanced pancreatic cancer (LAPC) who received IORT as part of their treatment at the Massachusetts General Hospital (MGH). METHODS: Medical records were reviewed for 194 consecutive patients with unresectable LAPC who were treated with IORT at MGH between 1978 and 2010. OS was calculated using the Kaplan-Meier method. Prognostic factors were evaluated at the univariate level by the log-rank test and at the multivariate level by the Cox proportional hazards model. Rates of disease progression and treatment toxicity were calculated. RESULTS: The 1-year, 2-year, and 3-year survival rates were 49%, 16%, and 6%, respectively. Six patients (3%) survived for > 5 years. The median OS was 12.0 months. Among 183 patients with known post-IORT disease status, the 2-year local progression-free survival and distant metastasis-free survival rates were 41% and 28%, respectively. On multivariate analysis, an IORT applicator diameter ≤ 8 cm (hazards ratio [HR], 0.51; 95% confidence interval [95% CI], 0.30-0.84 [P = .009]), a Charlson age-comorbidity index ≤ 3 (HR, 0.47; 95% CI, 0.31-0.73 [P = .001]), and receipt of chemotherapy (HR, 0.46; 95% CI, 0.33-0.66 [P < .001]) predicted improved OS. The median OS for patients with all 3 positive prognostic factors was 21.2 months. CONCLUSIONS: Well-selected patients with LAPC with small tumors and low Charlson age-comorbidity indices can achieve good long-term survival outcomes with a treatment regimen that incorporates chemotherapy and IORT.

Localized therapy for male breast cancer: functional advantages with comparable outcomes using breast conservation.

BACKGROUND: Male breast cancer (MBC) accounts for approximately 1% of all breast cancers. Given the rarity of this disease, treatment of MBC generally follows the same principles as treatment of female breast cancer. However, the traditional surgical approach for MBC is modified radical mastectomy (MRM) or total simple mastectomy (TSM) instead of breast conservation surgery (BCS). The purpose of this study was to examine the feasibility of BCS as an alternative to mastectomy for MBC with respect to musculoskeletal functionality and treatment outcome. PATIENTS AND METHODS: A retrospective analysis was undertaken of all male patients with breast cancer who presented to Massachusetts General Hospital or Boston Medical Center for localized therapy from 1990 to 2003. Musculoskeletal functionality (tissue fibrosis, arm edema, and range of motion) and treatment outcome (local-regional control, disease-free survival, and overall survival) were evaluated. Functional/cosmetic outcomes were assessed by multidisciplinary review of patient follow-up visits and were scored as either "good-excellent" or "fair-poor" to account for subjectivity between different clinicians. RESULTS: Forty-two patients in total were identified to undergo localized treatment. Thirty patients (71%) received MRM, 4 (10%) had TSM, and 8 (19%) underwent BCS. Actuarial overall 1-year fair-poor documented tissue fibrosis, arm edema, and decreased range of motion rates were 13%, 23%, and 27% for patients receiving MRM; 25%, 0%, and 50% for patients who underwent TSM; and 13%, 0%, and 0% for those undergoing BCS, respectively. Overall survival and disease-free survival were not statistically different between the groups. CONCLUSIONS: These data suggest that breast conservation therapy may be considered a reasonable local treatment option for male patients presenting with breast cancer because it may offer functional advantages over mastectomy with comparable rates of local control and disease-free survival and overall survival.

Performance of primary care physicians and other providers on key process measures in the treatment of diabetes.

OBJECTIVE: Studies have shown that patients without a consistent primary care provider have inferior outcomes. However, little is known about the mechanisms for these effects. This study aims to determine whether primary care physicians (PCPs) provide more frequent medication intensification, lifestyle counseling, and patient encounters than other providers in the primary care setting. RESEARCH DESIGN AND METHODS: This retrospective cohort study included 584,587 encounters for 27,225 patients with diabetes and elevated A1C, blood pressure, and/or LDL cholesterol monitored for at least 2 years. Encounters occurred at primary care practices affiliated with two teaching hospitals in eastern Massachusetts. RESULTS: Of the encounters documented, 83% were with PCPs, 13% were with covering physicians, and 5% were with midlevel providers. In multivariable analysis, the odds of medication intensification were 49% (P < 0.0001) and 26% (P < 0.0001) higher for PCPs than for covering physicians and midlevel providers, respectively, whereas the odds of lifestyle counseling were 91% (P < 0.0001) and 21% (P = 0.0015) higher. During visits with acute complaints, covering physicians were even less likely, by a further 52% (P < 0.0001), to intensify medications, and midlevel providers were even less likely, by a further 41% (P < 0.0001), to provide lifestyle counseling. Compared with PCPs, the hazard ratios for time to the next encounter after a visit without acute complaints were 1.11 for covering physicians and 1.19 for midlevel providers (P < 0.0001 for both). CONCLUSIONS: PCPs provide better care through higher rates of medication intensification and lifestyle counseling. Covering physicians and midlevel providers may enable more frequent encounters when PCP resources are constrained.