Should patients with hormone receptor-positive, HER2-negative breast cancer and one or two positive sentinel nodes undergo axillary dissection to determine candidacy for adjuvant abemaciclib?

BACKGROUND: The monarchE trial demonstrated improved outcomes with the use of adjuvant abemaciclib in patients with high-risk hormone receptor-positive, HER2-negative (HR+/HER2-) breast cancer defined as ≥4 positive lymph nodes (+LNs) or one to three +LNs with one or more additional high-risk features (HRFs). The proportion of patients with one or two positive sentinel lymph nodes (+SLNs) without HRFs who had ≥4 +LNs at the time of completion axillary lymph node dissection (cALND), and who therefore qualified for receipt of abemaciclib, was investigated. METHODS: Females with pathologically node-positive nonmetastatic HR+/HER2- breast cancer stratified by the number of +SLNs and +LNs and the presence of one or more HRFs were identified from the National Cancer Database (2018-2019). The proportion of patients meeting the criteria for abemaciclib both before and after ALND was assessed. RESULTS: Of the 22,048 patients identified, 1578 patients underwent upfront surgery, had one or two +SLNs without HRFs, and went on to cALND. Only 213 (13%) of these patients had ≥4 +LNs; thus, cALND performed solely to determine abemaciclib candidacy would have constituted surgical overtreatment in 1365 patients (87%). When stratified by the number of +SLNs, only 10% of those with one +SLN and 24% of those with two +SLNs had ≥4 +LNs after cALND, which meets the criteria for abemaciclib. CONCLUSIONS: Patients with one +SLN without HRFs are unlikely to have ≥4 +LNs and should not be subjected to the morbidity of ALND in order to inform candidacy for abemaciclib. An individualized multidisciplinary discussion should be undertaken about the risk:benefit ratio of ALND and abemaciclib for those with two +SLNs.

Pathological and Clinical Outcomes in a Large Surveillance and Intervention Cohort of Radiographically Cystic Renal Masses.

PURPOSE: We evaluated oncologic risks in a large cohort of patients with radiographic cystic renal masses who underwent active surveillance or intervention. MATERIALS AND METHODS: A single-institutional database of 4,340 kidney lesions managed with either active surveillance or intervention between 2000-2020 was queried for radiographically cystic renal masses. Association of radiographic tumor characteristics and high-grade pathology was evaluated. RESULTS: We identified 387 radiographically confirmed cystic lesions in 367 patients. Of these, 247 were resected (n=240) or ablated (n=7; n=247, 203 immediate vs 44 delayed intervention). Pathologically, 23% (n=56) demonstrated high-grade pathology. Cystic features were explicitly described by pathology in only 18% (n=33) of all lesions and in 7% (n=4) of high-grade lesions. Of the intervention cohort, African American race, male gender, and Bosniak score were associated with high-grade pathology (P < .05). On active surveillance (n=184), Bosniak IV lesions demonstrated faster growth rates than IIF and III lesions (2.7 vs 0.6 and 0.5 mm/y, P ≤ .001); however, growth rates were not associated with high-grade pathology (P = .5). No difference in cancer-specific survival was identified when comparing intervention vs active surveillance at 5 years (99% vs 100%, P = .2). No difference in recurrence was observed between immediate intervention vs delayed intervention (P > .9). CONCLUSIONS: A disconnect between "cystic" designation on imaging and pathology exists for renal lesions. Over 80% of radiographic Bosniak cystic lesions are not described as "cystic" on pathology reports. More than 1 in 5 resected cystic renal lesions demonstrated high-grade disease. Despite this finding, judiciously managed active surveillance ± delayed intervention is a safe and effective management option for most radiographic cystic renal masses.

The Impact of an Electromagnetic Seed Localization Device Versus Wire Localization on Breast-Conserving Surgery: A Matched-Pair Analysis.

BACKGROUND: For breast-conserving surgery (BCS), several alternatives to wire localization (WL) have been developed. The newest, electromagnetic seed localization (ESL), provides three-dimensional navigation using the electrosurgical tool. This study assessed operative times, specimen volumes, margin positivity, and re-excision rates for ESL and WL. METHODS: Patients who had ESL-guided breast-conserving surgery between August 2020 and August 2021 were reviewed and matched one-to-one with patients who had WL based on surgeon, procedure type, and pathology. Variables were compared between ESL and WL using Wilcoxon rank-sum and Fisher's exact tests. RESULTS: The study matched 97 patients who underwent excisional biopsy (n = 20) or partial mastectomy with (n = 53) or without (n = 24) sentinel lymph node biopsy (SLNB) using ESL. The median operative time for ESL versus WL for lumpectomy was 66 versus 69 min with SLNB (p = 0.76) and 40 versus 34.5 min without SLNB (p = 0.17). The median specimen volume was 36 cm3 using ESL versus 55 cm3 using WL (p = 0.001). For the patients with measurable tumor volume, excess tissue was greater using WL versus ESL (median, 73.2 vs. 52.5 cm3; p = 0.017). The margins were positive for 10 (10 %) of the 97 ESL patients and 18 (19 %) of the 97 WL patients (p = 0.17). In the ESL group, 6 (6 %) of the 97 patients had a subsequent re-excision compared with 13 (13 %) of the 97 WL patients (p = 0.15). CONCLUSIONS: Despite similar operative times, ESL is superior to WL, as evidenced by decreased specimen volume and excess tissue excised. Although the difference was not statistically significant, ESL resulted in fewer positive margins and re-excisions than WL. Further studies are needed to confirm that ESL is the most advantageous of the two methods.

The Impact of Radiotherapy Delay in Breast Conservation Patients Not Receiving Chemotherapy and the Rationale for Dichotomizing the Radiation Oncology Time-Dependent Standard into Two Quality Measures.

INTRODUCTION: The Commission on Cancer/National Quality Forum breast radiotherapy quality measure establishes that for women < 70 years, adjuvant radiotherapy after breast conserving surgery (BCS) should be started < 1 year from diagnosis. This was intended to prevent accidental radiotherapy omission or delay due to a long interval between surgery and chemotherapy completion, when radiation is delivered. However, the impact on patients not receiving chemotherapy, who proceed from surgery directly to radiotherapy, remains unknown. PATIENTS AND METHODS: Patients aged 18-69, diagnosed with stage I-III breast cancer as their first and only cancer diagnosis (2004-2016), having BCS, for whom this measure would be applicable, were reviewed from the National Cancer Database. RESULTS: Among 308,521 patients, the median age was 57.0 years, and > 99% of all patients were compliant with the measure. The cohort of interest included 186,650 (60.5%) patients not receiving chemotherapy, with a mean age of 57.9 years. Of these, 90.5% received external beam radiotherapy (EBRT) and 9.5% brachytherapy. Among them, 24.9% started radiotherapy > 8 weeks after surgery. In a multivariable model, delay from surgery to radiotherapy increased the hazard ratios for overall survival to 9.0% (EBRT) per month and 3.0% (brachytherapy) per week. CONCLUSION: While 99.9% of patients undergoing BCS without chemotherapy remain compliant with the current quality measure, 25% have delays > 8 weeks to start radiation, which is associated with impaired survival. These data suggest that the current quality measure should be dichotomized into two, with or without chemotherapy, in order to impel prompt radiotherapy initiation and maximize outcomes in all patients.

Adverse Events Reported by Patients With Cancer After Administration of a 2-Dose mRNA COVID-19 Vaccine.

BACKGROUND: Most safety and efficacy trials of the SARS-CoV-2 vaccines excluded patients with cancer, yet these patients are more likely than healthy individuals to contract SARS-CoV-2 and more likely to become seriously ill after infection. Our objective was to record short-term adverse reactions to the COVID-19 vaccine in patients with cancer, to compare the magnitude and duration of these reactions with those of patients without cancer, and to determine whether adverse reactions are related to active cancer therapy. PATIENTS AND METHODS: A prospective, single-institution observational study was performed at an NCI-designated Comprehensive Cancer Center. All study participants received 2 doses of the Pfizer BNT162b2 vaccine separated by approximately 3 weeks. A report of adverse reactions to dose 1 of the vaccine was completed upon return to the clinic for dose 2. Participants completed an identical survey either online or by telephone 2 weeks after the second vaccine dose. RESULTS: The cohort of 1,753 patients included 67.5% who had a history of cancer and 12.0% who were receiving active cancer treatment. Local pain at the injection site was the most frequently reported symptom for all respondents and did not distinguish patients with cancer from those without cancer after either dose 1 (39.3% vs 43.9%; P=.07) or dose 2 (42.5% vs 40.3%; P=.45). Among patients with cancer, those receiving active treatment were less likely to report pain at the injection site after dose 1 compared with those not receiving active treatment (30.0% vs 41.4%; P=.002). The onset and duration of adverse events was otherwise unrelated to active cancer treatment. CONCLUSIONS: When patients with cancer were compared with those without cancer, few differences in reported adverse events were noted. Active cancer treatment had little impact on adverse event profiles.

Total Neoadjuvant Treatment for Pancreatic Ductal Adenocarcinoma Is Associated With Limited Lymph Node Yield but Improved Ratio.

INTRODUCTION: The lymph node yield (LNY) and lymph node ratio (LNR) of nodal metastases following pancreatoduodenectomy (PD) have been reported as prognostic parameters in patients with pancreatic ductal adenocarcinoma (PDAC). However, they have not been compared in the setting of various neoadjuvant therapy modalities. METHODS: A single institutional retrospective study identified 134 patients diagnosed with resectable, BLR- and LA-PDAC who underwent PD at Fox Chase Cancer Center between 2010 and 2019. Patients were categorized based on first-line treatment as follows: surgery first (SF), total neoadjuvant therapy (TNT), and single modality neoadjuvant therapy (SMNT). The histopathological reports of the surgical specimens were examined to obtain LNY and determine the counts of lymph nodes with metastases. Subsequently, LNR was calculated as the number of positive lymph nodes divided by the number of lymph nodes examined. RESULTS: Overall, 49, 38, 27, 12, and 8 patients underwent SF approach, SMNT, incomplete TNT, induction TNT, and consolidation TNT, respectively. There was no difference in R0 resection and vascular resection between the groups (P = 0.096 and 0.794, respectively). The median counts of LNY were 22, 15, 21, 11.5, and 10, respectively (P < 0.001). The average LNR was 0.16, 0.07, 0.03, 0.02, and 0.02, respectively (P < 0.001). There were statistically significant differences in overall survival in the TNT groups (log-rank test P = 0.030). CONCLUSIONS: PDAC patients who undergo the TNT modality exhibit lower LNY and improved LNR compared with the SF approach and SMNT neoadjuvant therapy groups. This is likely explained by the increased treatment response and lymph node obliteration associated with the TNT approach. Our results question the minimal requirement of 11-18 harvested lymph nodes for PD following TNT.

Total neoadjuvant therapy is associated with improved overall survival and pathologic response in pancreatic adenocarcinoma.

BACKGROUND: Few studies have evaluated outcomes of total neoadjuvant therapy (TNT) compared with single modality neoadjuvant therapy (SMNT) or surgery first (SF) for pancreatic ductal adenocarcinoma (PDAC). METHODS: A single-institution retrospective review of PDAC patients who underwent pancreatectomy was conducted (1993-2019). Overall survival (OS) estimates from diagnosis and from surgery were determined using Kaplan-Meier methods; Cox proportional hazards models adjusted for covariates. RESULTS: Surgery was performed upfront (SF) in 168 (46.9%), while 111 (31.0%) had chemotherapy or chemoradiation before resection (SMNT), and 79 (22.1%) underwent TNT (chemotherapy and chemoradiation). Resection margins were more frequently R0 in the TNT group (86.1%) compared with SMNT (64.0%) and SF (72%) (p < 0.001). Complete pathologic response was more common in the TNT group (10.1%) compared with SMNT (3.6%) or SF (0.6%) (p = 0.001), resulting in prolonged survival (median OS = 100.2 months). TNT patients demonstrated longer median OS from surgery (33.6 months) compared with SF (19.1 months) and SMNT (17.4 months) (p = 0.010), which persisted after controlling for covariates. CONCLUSIONS: TNT is associated with more frequent complete pathologic response, a higher rate of margin negative resection, and prolonged OS as compared with SF or SMNT. Additional studies to identify subgroups that derive the greatest benefit are warranted.

Breakfast in the Classroom Initiative and Students' Breakfast Consumption Behaviors: A Group Randomized Trial.

Objectives. To identify the effect of a Breakfast in the Classroom (BIC) initiative on the foods and drinks students consume in the morning.Methods. Sixteen public schools in Philadelphia, Pennsylvania, that provide universal breakfast participated in a group randomized trial to examine the effects of BIC with complementary nutrition promotion between 2013 and 2016. Control schools (n = 8) offered breakfast in the cafeteria before school. Baseline data were collected from 1362 students in grades 4 to 6. Endpoint data were collected after 2.5 years. Students self-reported the foods and drinks they consumed in the morning.Results. At endpoint, there was no effect of the intervention on breakfast skipping. Nearly 30% of intervention students consumed breakfast foods or drinks from multiple locations, as compared with 21% of control students. A greater proportion of intervention students than control students consumed 100% juice, and a smaller proportion consumed sugar-sweetened beverages and foods high in saturated fat and added sugar.Conclusions. A BIC initiative led to improvements in the types of foods and drinks students consumed in the morning. However, the program did not reduce breakfast skipping and increased the number of locations where students ate.

Title: efficacy of a food parenting intervention for mothers with low income to reduce preschooler's solid fat and added sugar intakes: a randomized controlled trial.

BACKGROUND: Few interventions have shown efficacy to influence key energy balance behaviors during the preschool years. OBJECTIVE: A randomized controlled trial (RCT) was used to evaluate the efficacy of Food, Fun, and Families (FFF), a 12 week authoritative food parenting intervention for mothers with low-income levels, to reduce preschool-aged children's intake of calories from solid fat and added sugar (SoFAS). METHODS: Mothers were randomly assigned to receive FFF (n = 59) or to a delayed treatment control (n = 60). The primary outcome was children's daily energy intake from SoFAS at the end of the 12 week intervention, controlling for baseline levels, assessed by 24-h dietary recalls. Secondary outcomes included children's daily energy intake, children's BMI z-scores, and meal observations of maternal food parenting practices targeted in FFF (e.g. providing guided choices). RESULTS: Participating mothers were predominantly African American (91%), with 39% educated beyond high school and 66% unemployed. Baseline demographics and child SoFAS intakes did not differ by group. Lost to follow-up was 13% and did not differ between groups. At post-intervention, FFF children consumed ~ 94 kcal or 23% less daily energy from SoFAS than children in the control group, adjusting for baseline levels (307.8 (95%CI = 274.1, 341.5) kcal vs. 401.9 (95%CI = 369.8, 433.9) kcal, FFF vs. control; p < 0.001). FFF mothers also displayed a greater number of authoritative parenting practices when observed post-intervention with their child at a buffet-style meal (Wilcoxon z = - 2.54, p = 0.012). Neither child total daily energy intake nor BMI z-scores differed between groups post-intervention. CONCLUSIONS: Findings demonstrate the initial efficacy of an authoritative food parenting intervention for families with low-income to reduce SoFAS intake in early childhood. Additional research is needed to evaluate longer-term effects on diet and growth. TRIAL REGISTRATION: Retrospectively registered at ClinicalTrials.gov : #NCT03646201.

Predictive Value of Leukocyte- and Platelet-Derived Ratios in Rectal Adenocarcinoma.

BACKGROUND: Advances in treatment of rectal cancer have improved survival, but there is variability in response to therapy. Recent data suggest the utility of the lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) in predicting survival. Our aim was to examine these ratios in rectal cancer patients and determine whether any association exists with overall survival (OS). METHODS: Using prospectively maintained institutional data, a query was completed for clinical stage II-III rectal adenocarcinoma patients treated from 2002 to 2016. We included patients who had a complete blood count collected before neoadjuvant chemoradiation (pre-CRT) and again before surgery (post-CRT). The LMR, NLR, and PLR were calculated for the pre-CRT and post-CRT time points. Potential cutpoints associated with OS differences were determined using maximally selected rank statistics. Survival curves were compared using log-rank tests and were adjusted for age and stage using Cox regression. RESULTS: A total of 146 patients were included. Cutpoints were significantly associated with OS for pre-CRT ratios but not for post-CRT ratios. Within the pretreatment group, a "low" (<2.86) LMR was associated with decreased OS (log-rank P = 0.004). In the same group, a "high" (>4.47) NLR and "high" PLR (>203.6) were associated with decreased OS (log-rank P < 0.001). With covariate adjustment for age, and separately for final pathologic stage, the associations between OS and LMR, NLR, and PLR each retained statistical significance. CONCLUSIONS: If obtained before the start of neoadjuvant chemoradiation, LMR, NLR, and PLR values are accurate predictors of 5-y OS in patients with locally advanced rectal adenocarcinoma.

Pathologic response following treatment for locally advanced rectal cancer: Does location matter?

BACKGROUND: Despite advances in the treatment of rectal adenocarcinoma, the management of locally advanced disease remains a challenge. The standard of care for patients with stages II and III rectal cancer includes neoadjuvant chemoradiation followed by total mesorectal excision and postoperative chemotherapy. Much effort has been dedicated to the identification of predictive factors associated with pathologic complete response (pCR). The aim of our study was to examine our institutional experience and determine whether any association exists between anatomic tumor location and the rate of pCR. We hypothesized that lesions more than 6 cm from the anal verge are more likely to achieve a pCR. METHODS: Using data from our prospectively maintained tumor registry, a query was completed to identify all patients with locally advanced rectal adenocarcinoma who underwent treatment at Fox Chase Cancer Center from 2002 to 2015. Demographics, pretreatment, posttreatment, and final pathologic TNM staging data were collected as well as treatment intervals in days, recurrence status, overall survival, and disease-free survival. Patients with incomplete endoscopic data, staging information, survival, or recurrence status were excluded. The primary outcome measured was the degree of pathologic response. Logistic regression was used to adjust for covariates. RESULTS: Of the 135 patients eligible in the study cohort, 39% were female and 61% were male. Regarding initial clinical stage, 43% were stage II and 57% were stage III. A total of 29% had a pCR, 43% had partial pathologic response, and 28% had no response to neoadjuvant treatment. Tumor location ranged from 0 to 13 cm from the anal verge. Longitudinal tumor length was recorded in 111 patients, facilitating the calculation of mean tumor distance from the anal verge. This ranged from 0 to 15.5 cm. Univariate and multivariable analyses were completed using pCR as a primary outcome. No statistically significant difference was noted based on tumor location, regardless of measurement approach. CONCLUSIONS: Anatomic location of cancer of the rectum does not affect pCR after neoadjuvant therapy and subsequent surgical resection.

LincIN, a novel NF90-binding long non-coding RNA, is overexpressed in advanced breast tumors and involved in metastasis.

BACKGROUND: Recent genome-wide profiling by sequencing and distinctive chromatin signatures has identified thousands of long non-coding RNA (lncRNA) species (>200 nt). LncRNAs have emerged as important regulators of gene expression, involving in both developmental and pathological processes. While altered expression of lncRNAs has been observed in breast cancer development, their roles in breast cancer progression and metastasis are still poorly understood. METHODS: To identify novel breast cancer-associated lncRNA candidates, we employed a high-density SNP array-based approach to uncover intergenic lncRNA genes that are aberrantly expressed in breast cancer. We first evaluated the potential value as a breast cancer prognostic biomarker for one breast cancer-associated lncRNA, LincIN, using a breast cancer cohort retrieved from The Cancer Genome Atlas (TCGA) Data Portal. Then we characterized the role of LincIN in breast cancer progression and metastasis by in vitro invasion assay and a mouse tail vein injection metastasis model. To study the action of LincIN, we identified LincIN-interacting protein partner(s) by RNA pull-down experiments followed with protein identification by mass spectrometry. RESULTS: High levels of LincIN expression are frequently observed in tumors compared to adjacent normal tissues, and are strongly associated with aggressive breast cancer. Importantly, analysis of TCGA data further suggest that high expression of LincIN is associated with poor overall survival in patients with breast cancer (P = 0.044 and P = 0.011 after adjustment for age). The functional experiments demonstrate that knockdown of LincIN inhibits tumor cell migration and invasion in vitro, which is supported by the results of transcriptome analysis in the LincIN-knockdown cells. Furthermore, knockdown of LincIN diminishes lung metastasis in a mouse tail vein injection model. We also identified a LincIN-binding protein, NF90, through which overexpression of LincIN may repress p21 protein expression by inhibiting its translation, and upregulation of p21 by LincIN knockdown may be associated with less aggressive metastasis phenotypes. CONCLUSIONS: Our studies provide clear evidence to support LincIN as a new regulator of tumor progression-metastasis at both transcriptional and translational levels and as a promising prognostic biomarker for breast cancer.

Mutational studies on single circulating tumor cells isolated from the blood of inflammatory breast cancer patients.

PURPOSE: The molecular characterization of circulating tumor cells (CTCs) is critical to identify the key drivers of cancer metastasis and devising therapeutic approaches, particularly for inflammatory breast cancer (IBC) which is usually diagnosed at advance stages and progresses rapidly. METHODS: Genomic alterations in tumor tissue samples were studied using Foundation One™. Single CTCs were isolated using CellSearch followed by single-cell isolation by DEPArray™. Samples with 20 or more CTCs were chosen to isolate single CTCs using the DEPArray™. RESULTS: Genomic alterations were studied in primary tumor or metastatic sites from 32 IBC patients. Genes with high-frequency mutations were as follows: TP53 (69%), RB1 (16%), PIK3CA (13%), and also ErbB2 (3%). At least once during treatment, CTCs were detected in 26 patients with metastatic IBC, in two patients with locally advanced IBC, and four patients had no detectable CTCs. Per 7.5 mL of blood, fifteen patients (47%) had ≥20 CTCs and six of them were chosen at random to isolate single CTCs. These cells were tested for the presence of TP53, RB1, PIK3CA, and/or ErbB2 mutations previously found in matching tissue biopsies. The isolated CTCs showed the same mutations as primary or metastatic tumor samples. Intra-patient CTC heterogeneity was found by the presence of different CTC subclones, with some CTCs harboring different combinations of mutated and wild-type genes. CONCLUSIONS: Our results indicate that CTCs could represent a non-invasive source of cancer cells from which to determine genetic markers as the disease progresses and identify potential therapeutic targets in IBC patients.

The need for androgen deprivation therapy in patients with intermediate-risk prostate cancer treated with dose-escalated external beam radiation therapy.

INTRODUCTION: To evaluate if androgen deprivation therapy (ADT) improves outcomes for patients with localized, intermediate-risk prostate cancer treated with definitive external beam radiation therapy (EBRT) in the dose-escalated era. MATERIALS AND METHODS: This is a retrospective study using a single institutional database. We included patients with localized, intermediate-risk prostate cancer treated with dose-escalated radiation therapy (RT) with 3D conformal radiotherapy or intensity-modulated radiotherapy (74-80 Gy in daily fraction of 1.8 Gy-2.0 Gy, or 70.2 Gy in daily fraction of 2.7 Gy) from 1992 to 2013. To further risk stratify the patients, PSA 10 ng/mL-20 ng/mL, Gleason 3+4, and T2b-T2c were assigned risk score (RS) of 1, while Gleason 4+3 was assigned RS of 2. Patients with prior treatment for prostate cancer, those on long term ADT (>= 23 months), or those with follow up < 1 year were excluded. We defined initial ADT as initiation within 9 months prior to the start of RT, during RT, or within 2 months after the completion of RT. Outcomes for patients who received initial ADT were compared to men treated with RT alone. Covariates included number of intermediate risk factors, age, and baseline comorbidities. Kaplan Meier estimates were compared using log rank tests. Competing risk regression and Cox proportional hazards regression were used to estimate hazard ratios adjusted for covariates. RESULTS: Of 1,134 patients included in this study, 155 received initial ADT with median duration of 4.0 months (m) (range 0.5 m-22.0 m). The median follow up was 56.4 m (range 12.3 m-200.7 m). Patients on ADT had higher RS compared to those with radiation alone (RS 1: 48% versus 58%; RS 2: 35% versus 32%; RS 3: 14% versus 9%; RS 4: 3% versus 1%; p=0.01). When patients with ADT were compared to those treated with radiation alone, there were no significant differences in freedom from biochemical failure (FFBF) (84.0% versus 87.3%, p = 0.83), freedom from distant metastasis (FFDM) (94.4% versus 96.9%, p = 0.41), or overall survival (OS) (92.3% versus 90.7%, (p = 0.48) at 5 years. Among patients with RS >= 2, there were still no significant differences in FFBF, FFDM, or OS when patients treated with ADT were compared to those treated with radiation alone. In multivariable analyses adjusting for RS and age, the adjusted hazard ratio for ADT use was sHR = 0.89 (95% CI = 0.64-1.66, p = 0.64) for BCF; sHR = 1.13 (95% CI = 0.48-2.65, p = 0.77) for DM. For overall mortality, adjusted HR = 1.23 (95% CI = 0.76-2.01, p = 0.40) where comorbidities (including diabetes, cardiac disease, and hypertension) were also included as covariates. CONCLUSION: Our study suggested that treatment of intermediate-risk prostate cancer with definitive dose-escalated EBRT alone resulted in acceptable outcomes, and it failed to show improved outcomes in patients who received short term ADT.

Breast conservation versus mastectomy for patients with T3 primary tumors (>5 cm): A review of 5685 medicare patients.

BACKGROUND: Although breast conservation therapy (BCT) is standard for breast cancer treatment, patients with tumors measuring >5 cm have been excluded from clinical trials. Nevertheless, only a few small retrospective series to date have compared BCT with mastectomy for tumors measuring >5 cm. The current study was performed to determine whether survival is equivalent for BCT versus mastectomy using a large national data set. METHODS: Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked cases were identified for patients aged ≥ 66 years undergoing breast conservation for invasive, noninflammatory, nonmetastatic breast cancer between 1992 and 2009. Propensity score-based adjustment was used to account for demographics and tumor and treatment factors. RESULTS: A total of 5685 patients with tumors measuring >5.0 cm underwent breast surgery, with 15.6% receiving BCT. Mean ages of the patients and tumor sizes were similar. Predictors of BCT included neoadjuvant chemotherapy and postoperative radiotherapy use, higher income, breast cancer as a first malignancy, and a higher Charlson Comorbidity Index. Predictors of mastectomy included younger age, nonductal histology, higher grade, numbers of lymph nodes examined and found to be positive, American Joint Committee on Cancer stage III disease, postoperative chemotherapy use, and residential region of the country. Adjusted overall and breast cancer-specific survival were not different between patients treated with BCT and mastectomy (hazard ratio, 0.934; 95% confidence interval, 0.791-1.103 [P = .419] for overall survival; and subdistribution hazard ratio, 1.042; 95% confidence interval, 0.793-1.369 [P = .769] for breast cancer-specific survival), with each improving over time. The median follow-up was 7.0 years. CONCLUSIONS: For Medicare patients with tumors measuring >5 cm, survival is similar between those treated with BCT and mastectomy as for patients with smaller primary tumors. Despite exclusion from randomized trials, BCT may remain an option for patients with larger tumors when deemed clinically and cosmetically amenable to surgical resection.

Patient reported outcomes among treatment modalities for prostate cancer.

INTRODUCTION: To characterize patient reported outcomes for urinary and sexual function using International Prostate Symptom Score (IPSS) and Sexual Health Inventory for Men (SHIM) comparing intensity modulated radiation therapy (IMRT), low dose rate brachytherapy (LDR), post-prostatectomy IMRT (PPRT), and radical prostatectomy (RP). MATERIALS AND METHODS: Patients treated for prostate cancer from 2001-2012 completed self-reported SHIM and IPSS surveys. Subgroups were created by baseline score. Mean change from baseline was determined at each time point for the cohort and subgroups. Statistical analysis was performed with generalized estimating equation method. Incontinence was not captured in the questionnaires. RESULTS: A total of 14,523 IPSS surveys from 3,515 men were evaluated. Patients treated with IMRT experienced a minimal decrease in IPSS score from baseline. PPRT scores did not differ from IMRT at any time point (range: +/- 3 points from baseline in IPSS score over 50 months). LDR had an initial IPSS rise (between 5-10 points on the IPSS over 1-9 months) versus IMRT but returned to comparable levels at 34 months. RP was associated with a lower IPSS versus IMRT. LDR had the largest rise from baseline, with return toward baseline. A total of 2,624 SHIM surveys from 857 men were evaluated. LDR and PPRT did not differ from IMRT at any time point (range: +/- 5 points from baseline in SHIM score for 36 months). RP experienced the largest decline from baseline (up to -7 points on SHIM score), at 3 to 7 months; RP had a larger early decrease in SHIM score versus IMRT between 3 and 22 months, after which there was no difference. CONCLUSIONS: IPSS and SHIM score patterns differed among treatment modalities. These data can be used to predict changes in urinary and sexual function over time based on modality and baseline score.

Impact of obesity on outcomes after definitive dose-escalated intensity-modulated radiotherapy for localized prostate cancer.

BACKGROUND: Previous publications have demonstrated conflicting results regarding body mass index (BMI) and prostate cancer (CaP) outcomes after definitive radiotherapy (RT) before the dose escalation era. The goal of the current study was to determine whether increasing BMI was associated with outcomes in men with localized CaP who were treated with dose-escalated RT. METHODS: The authors identified patients with localized (T1b-T4N0M0) CaP who were treated with definitive intensity-modulated RT and image-guided RT from 2001 through 2010. BMI was analyzed as a continuous variable. Adjusting for confounders, multivariable competing risk and Cox proportional hazards regression models were used to assess the association between BMI and the risk of biochemical failure (BF), distant metastases (DM), cause-specific mortality (CSM), and overall mortality. RESULTS: Of the 1442 patients identified, approximately 20% had a BMI <25 kg/m(2) , 48% had a BMI of 25 to 29.9 kg/m(2) , 23% had a BMI of 30 to 34.9 kg/m(2) , 6% had a BMI of 35 to 39.9 kg/m(2) , and 4% had a BMI of ≥40 kg/m(2) . The median follow-up was 47.6 months (range, 1-145 months), with a median age of 68 years (range, 36-89 years). The median dose was 78 grays (range, 76-80 grays) and 30% of patients received androgen deprivation therapy. Increasing BMI was found to be inversely associated with age (P<.001) and pretreatment prostate-specific antigen level (P = .018). On multivariable analysis, increasing BMI was associated with an increased risk of BF (hazard ratio [HR], 1.03; 95% confidence interval [95% CI], 1.00-1.07 [P = .042]), DM (HR, 1.07; 95% CI, 1.02-1.11 [P = .004]), CSM (HR, 1.15; 95% CI, 1.07-1.23 [P<.001]), and overall mortality (HR, 1.05; 95% CI, 1.02-1.08 [P = .004]). CONCLUSIONS: For patients with CaP receiving dose-escalated intensity-modulated RT with daily image-guidance, increasing BMI appears to be associated with an increased risk of BF, DM, CSM, and overall mortality.

Association of treatment factors with surgical outcomes in tri-modality therapy for esophageal cancer.

BACKGROUND AND OBJECTIVES: To identify the impact of the interval between chemoradiation to surgery on morbidity and mortality in patients undergoing tri-modality therapy for esophageal cancer. METHODS: Eighty-five patients completed chemoradiation followed by esophagectomy between 2006 and 2011. The interval between completion of chemoradiation and surgery was calculated for each patient. We evaluated the association of quartiles and 3-week groups with morbidity and mortality using logistic regression. Other treatment and clinical factors were also assessed. RESULTS: A total of 59 patients(69%) experienced at least one complication. When examining specific complications, patients with pulmonary complications had a longer mean time interval from chemoradiation to surgery (P = 0.02). Linear regression showed an association between longer interval between chemoradiation to surgery and hospital length of stay (LOS) >14 days when analyzing by both interval quartile (P = 0.04) and 3-week intervals (P = 0.04). On multivariable analysis, increased time interval predicted for pulmonary complications (P < 0.01) and LOS >14 days (P = 0.03). When examining other treatment factors, squamous cell histology (P = 0.02) also predicted for a hospital length of stay >14 days. CONCLUSIONS: Factors such as interval between completion of chemoradiation and surgery and squamous cell histology may be associated with surgical morbidity. Further data is warranted to confirm these findings.

Effects of genetic and environmental risk assessment feedback on colorectal cancer screening adherence.

Little is known about the impact of genetic and environmental risk assessment (GERA) feedback on colorectal cancer (CRC) screening. In a recently completed randomized trial, primary care patients received GERA feedback based on a blood test for genetic polymorphisms and serum folate level (GERA Group) versus usual care (Control Group). Subsequently, participants were offered CRC screening. Among participants who received GERA feedback, being at elevated risk was negatively associated with prospective CRC screening adherence. Secondary analyses of data from this study were performed to identify independent predictors of adherence among participants who received GERA feedback. We obtained baseline survey, follow-up survey, and endpoint medical records data on sociodemographic background, knowledge, psychosocial characteristics, risk status, and adherence for 285 GERA Group participants. Univariate and multivariable analyses were performed to identify predictors of CRC screening adherence. Following a 6-month outcomes observation period, we also conducted two focus groups with GERA Group participants to assess their perceptions of GERA risk feedback and screening. Content analyses of focus group data were evaluated to gain insights into participant response to risk feedback. Overall, half of GERA Group participants adhered to screening within 6 months after randomization. Multivariable analyses showed a statistically significant interaction between race and GERA feedback status relative to screening adherence (p = 0.043). Among participants who received average risk feedback, adherence was comparable among whites (49.7 %) and nonwhites (54.1 %); however, among those at elevated risk, adherence was substantially higher among whites (66.7 %) compared to nonwhites (33.3 %). Focus group findings suggest that whites were more likely than nonwhites to view elevated risk feedback as a prompt to screen. In response to receiving elevated risk feedback, nonwhites were more likely than whites to report feeling anxiety about the likelihood of being diagnosed with CRC. Further research is needed to explore race-related CRC screening differences in response to GERA feedback.