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.

Factors Associated with Reconstruction Failure and Major Complications After Postmastectomy Radiation to a Reconstructed Breast.

PURPOSE: Postmastectomy radiation therapy is known to increase risk of complications in the reconstruction setting. We aim to identify the variables associated with reconstruction failure and other major complications. METHODS AND MATERIALS: A prospectively collected institutional database was queried for patients with up to stage IIIC breast cancer treated from 2000 to 2017, undergoing mastectomy, immediate implant or autologous tissue reconstruction, and radiation to the reconstructed breast within 1 year of surgery. Reconstruction failure was defined as complication requiring surgical revision or implant removal. Additional major complications were defined as any infection, contracture, necrosis, or fibrosis. Covariates of interest included age, body mass index, smoking status, stage, hormone receptor and HER2 status, systemic therapy timing, radiation technique, nodal irradiation, and interval between surgery and start of postmastectomy radiation therapy. Differences in complication rates were assessed with χ² or Fisher exact tests. Competing risk regression was used to estimate hazard ratios; covariates were included one at a time to avoid over adjustment. RESULTS: A total of 206 reconstructed breasts in 202 patients resulted from our initial query, with 139 treated with intensity-modulated radiation therapy (IMRT) and 67 treated with conventional radiation therapy (CRT). Median follow-up was 45 months (range, 4-210 months); patient cohorts were generally similar. Eight patients were excluded from toxicity analysis for insufficient follow-up (<2 years). Overall, reconstruction failure and major complication rates were significantly lower in the IMRT group. Reconstruction failure rates were 3.0% for IMRT versus 16.4% for CRT (P = .002), and major complication rates were 6.8% for IMRT versus 24.6% for CRT (P < .001). On univariate analysis, CRT was significantly predictive of implant failure (hazard ratio, 5.54; P = .003) and increased complication rates (hazard ratio, 3.83; P = .001). Significance persisted on multivariable analysis. Survival outcomes were similar, with no difference in 2 year overall survival (P = .12) and local recurrence (P = .41). CONCLUSIONS: Using IMRT may improve reconstruction outcomes over CRT, with significantly lower reconstruction failure and complication rates without compromising local control or survival.

A tool to predict disparities in the timeliness of surgical treatment for breast cancer patients in the USA.

PURPOSE: Breast cancer outcomes are impaired by both delays and disparities in treatment. This study was performed to assess their relationship and to provide a tool to predict patient socioeconomic factors associated with risk for delay. METHODS: The National Cancer Database was reviewed between 2004 and 2017 for patients with non-metastatic breast cancer managed with upfront surgery. Times to treatment were measured from the date of diagnosis. Patient, tumor, and treatment factors were assessed with attention paid to sociodemographic variables. RESULTS: 514,187 patients remained after exclusions, with 84.3% White, 10.8% Black, 3.7% Asian, and Hispanics comprising 5.6% of the cohort. Medicaid and uninsured patients had longer mean adjusted time to surgery (≥ 46 days) versus private (36.7 days), Medicare (35.9 days), or other governmental insurance (39.8 days). After adjustment, Black race and Hispanic ethnicity were most impactful, adding 6.0 and 6.4 preoperative days, 10.9 and 11.5 days to chemotherapy, 11.1 and 9.1 days to radiation, and 12.5 and 8.9 days to endocrine therapy, respectively. Income, education, and insurance, among other factors, also affected delay. A nomogram, including race and sociodemographic factors, was created to predict the risk of preoperative delay. CONCLUSION:  Significant disparities exist in timeliness of care for factors, including but not limited to, race and ethnicity. Although exact causes cannot be discerned, these data indicate population subsets whose intervals of care risk being longer than those specified by national quality standards. The nomogram created here may help direct resources to those at highest risk of incurring a treatment delay.

Neoadjuvant Endocrine Therapy and Delays in Surgery for Ductal Carcinoma in Situ: Implications for the Coronavirus Pandemic.

BACKGROUND: Surgical delays are associated with invasive cancer for patients with ductal carcinoma in situ (DCIS). During the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) pandemic, neoadjuvant endocrine therapy (NET) was used as a bridge until postponed surgeries resumed. This study sought to determine the impact of NET on the rate of invasive cancer for patients with a diagnosis of DCIS who have a surgical delay compared with those not treated with NET. METHODS: Using the National Cancer Database, the study identified women with hormone receptor-positive (HR+) DCIS. The presence of invasion on final pathology was evaluated after stratifying by receipt of NET and by intervals based on time from diagnosis to surgery (≤30, 31-60, 61-90, 91-120, or 121-365 days). RESULTS: Of 109,990 women identified with HR+ DCIS, 276 (0.3%) underwent NET. The mean duration of NET was 74.4 days. The overall unadjusted rate of invasive cancer was similar between those who received NET ((15.6%) and those who did not (12.3%) (p = 0.10). In the multivariable analysis, neither the use nor the duration of NET were independently associated with invasion, but the trend across time-to-surgery categories demonstrated a higher rate of upgrade to invasive cancer in the no-NET group (p < 0.001), but not in the NET group (p = 0.97). CONCLUSIONS: This analysis of a pre-COVID cohort showed evidence for a protective effect of NET in HR+ DCIS against the development of invasive cancer as the preoperative delay increased, although an appropriately powered prospective trial is needed for a definitive answer.

Use of Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer: Initial Results From the Pembrolizumab Arm of a Phase 2 Randomized Clinical Trial.

IMPORTANCE: Total neoadjuvant therapy (TNT) is often used to downstage locally advanced rectal cancer (LARC) and decrease locoregional relapse; however, more than one-third of patients develop recurrent metastatic disease. As such, novel combinations are needed. OBJECTIVE: To assess whether the addition of pembrolizumab during and after neoadjuvant chemoradiotherapy can lead to an improvement in the neoadjuvant rectal (NAR) score compared with treatment with FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) and chemoradiotherapy alone. DESIGN, SETTING, AND PARTICIPANTS: In this open-label, phase 2, randomized clinical trial (NRG-GI002), patients in academic and private practice settings were enrolled. Patients with stage II/III LARC with distal location (cT3-4 ≤ 5 cm from anal verge, any N), with bulky disease (any cT4 or tumor within 3 mm of mesorectal fascia), at high risk for metastatic disease (cN2), and/or who were not candidates for sphincter-sparing surgery (SSS) were stratified based on clinical tumor and nodal stages. Trial accrual opened on August 1, 2018, and ended on May 31, 2019. This intent-to-treat analysis is based on data as of August 2020. INTERVENTIONS: Patients were randomized (1:1) to neoadjuvant FOLFOX for 4 months and then underwent chemoradiotherapy (capecitabine with 50.4 Gy) with or without intravenous pembrolizumab administered at a dosage of 200 mg every 3 weeks for up to 6 doses before surgery. MAIN OUTCOMES AND MEASURES: The primary end point was the NAR score. Secondary end points included pathologic complete response (pCR) rate, SSS, disease-free survival, and overall survival. This report focuses on end points available after definitive surgery (NAR score, pCR, SSS, clinical complete response rate, margin involvement, and safety). RESULTS: A total of 185 patients (126 [68.1%] male; mean [SD] age, 55.7 [11.1] years) were randomized to the control arm (CA) (n = 95) or the pembrolizumab arm (PA) (n = 90). Of these patients, 137 were evaluable for NAR score (68 CA patients and 69 PA patients). The mean (SD) NAR score was 11.53 (12.43) for the PA patients (95% CI, 8.54-14.51) vs 14.08 (13.82) for the CA patients (95% CI, 10.74-17.43) (P = .26). The pCR rate was 31.9% in the PA vs 29.4% in the CA (P = .75). The clinical complete response rate was 13.9% in the PA vs 13.6% in the CA (P = .95). The percentage of patients who underwent SSS was 59.4% in the PA vs 71.0% in the CA (P = .15). Grade 3 to 4 adverse events were slightly increased in the PA (48.2%) vs the CA (37.3%) during chemoradiotherapy. Two deaths occurred during FOLFOX: sepsis (CA) and pneumonia (PA). No differences in radiotherapy fractions, FOLFOX, or capecitabine doses were found. CONCLUSIONS AND RELEVANCE: Pembrolizumab added to chemoradiotherapy as part of total neoadjuvant therapy was suggested to be safe; however, the NAR score difference does not support further study. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02921256.

Breast Reconstruction in Inflammatory Breast Cancer: An Analysis of Predictors, Trends, and Survival from the National Cancer Database.

INTRODUCTION: Survival for women diagnosed with inflammatory breast cancer (IBC) has improved with advances in multimodal therapy. This study was performed to evaluate trends, predictors, and survival for reconstruction in IBC patients in the United States. METHODS: Women who underwent mastectomy with or without reconstruction for IBC between 2004 and 2016 were included from the National Cancer Database. Predictors for undergoing reconstruction and association with overall survival were determined. RESULTS: Of 12,544 patients with IBC who underwent mastectomy, 1307 underwent reconstruction. Predictors of reconstruction included younger age, private insurance, higher income, performance of contralateral prophylactic mastectomy, and location within a metropolitan area (P < 0.001). The proportion of women having reconstruction for IBC increased from 7.3% to 12.3% from 2004 to 2016. Median unadjusted overall survival was higher in the reconstructive group l [93.7 months, 95% confidence interval (CI) 75.2-117.5] than the nonreconstructive group (68.1 months, 95% CI 65.5-71.7, hazard ratio = 0.79 95% CI 0.72-0.88, P < 0.001). With adjustment for covariates, differences in overall mortality were not significant, with hazard ratio of 0.95 (95% CI 0.85-1.06, P = 0.37). CONCLUSIONS: Reconstruction rates for IBC are increasing. Women with IBC who undergo reconstruction tend to be younger and are not at the increased risk of all-cause mortality compared to those not having reconstruction. The National Cancer Database does not differentiate immediate from delayed reconstruction. However, the outcomes of immediate reconstruction in carefully selected patients with IBC should be further studied to evaluate its safety. This could impact current guidelines, which are based largely on an expert opinion.

Evaluation of Safety of Stereotactic Body Radiotherapy for the Treatment of Patients With Multiple Metastases: Findings From the NRG-BR001 Phase 1 Trial.

IMPORTANCE: Stereotactic body radiotherapy (SBRT) for oligometastases is hypothesized to improve survival and is increasingly used. Little evidence supports its safe use to treat patients with multiple metastases. OBJECTIVE: To establish safety of SBRT dose schedules in patients with 3 to 4 metastases or 2 metastases in close proximity to each other. DESIGN, SETTING, AND PARTICIPANTS: This phase 1 trial opened on August 4, 2014, and closed to accrual on March 20, 2018. Metastases to 7 anatomic locations were included: bone/osseous (BO), spinal/paraspinal (SP), peripheral lung (PL), central lung (CL), abdominal-pelvic (AP), mediastinal/cervical lymph node (MC), and liver (L). Six patients could be enrolled per anatomic site. The setting was a consortium of North American academic and community practice cancer centers participating in NRG Oncology trials. Patients with breast, prostate, or non-small cell lung cancer with 3 to 4 metastases or 2 metastases in close proximity (≤5 cm) amenable to SBRT were eligible for this phase 1 study. Statistical analyses were performed from December 31, 2017, to September 19, 2019. INTERVENTIONS: The starting dose was 50 Gy in 5 fractions (CL, MC), 45 Gy in 3 fractions (PL, AP, L), and 30 Gy in 3 fractions (BO, SP). MAIN OUTCOMES AND MEASURES: The primary end point was dose-limiting toxicity (DLT) defined by the Common Terminology Criteria for Adverse Events, version 4.0, as specific adverse events (AEs) of grades 3 to 5 (definite or probable per the protocol DLT definition) related to SBRT within 180 days of treatment. Dose levels were considered safe if DLTs were observed in no more than 1 of 6 patients per location; otherwise, the dose at that location would be de-escalated. RESULTS: A total of 42 patients enrolled, 39 were eligible, and 35 (mean [SD] age, 63.1 [14.2] years; 20 men [57.1%]; 30 White patients [85.7%]) were evaluable for DLT. Twelve patients (34.3%) had breast cancer, 10 (28.6%) had non-small cell lung cancer, and 13 (37.1%) had prostate cancer; there was a median of 3 metastases treated per patient. Median survival was not reached. No protocol-defined DLTs were observed. When examining all AEs, 8 instances of grade 3 AEs, most likely related to protocol therapy, occurred approximately 125 to 556 days from SBRT initiation in 7 patients. CONCLUSIONS AND RELEVANCE: This phase 1 trial demonstrated the safety of SBRT for patients with 3 to 4 metastases or 2 metastases in close proximity. There were no treatment-related deaths. Late grade 3 AEs demonstrate the need for extended follow-up in long-surviving patients with oligometastatic disease. Treatment with SBRT for multiple metastases has been expanded into multiple ongoing randomized phase 2/3 National Cancer Institute-sponsored trials (NRG-BR002, NRG-LU002). TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02206334.

Does the false-negative rate for 1 or 2 negative sentinel nodes after neo-adjuvant chemotherapy translate into a high local recurrence rate?

Prospective trials demonstrate that sentinel node (SN) biopsy after neo-adjuvant chemotherapy (NACT) has a significant false-negative rate (FNR) when only 1 or 2 SNs are removed. It is unknown whether this increased FNR correlates with an elevated risk of recurrence. Tumor Registry data at an NCI-Designated Comprehensive Cancer Center were reviewed from 2004 to 2018 for patients having a negative SN biopsy after NACT. Among 190 patients with histologically negative nodes after NACT having 1 (n = 42), 2 (n = 46), and ≥3 (n = 102) SNs, axillary recurrences occurred in 7.14%, 0%, and 1.96% (p = 0.09), breast recurrences occurred in 2.38%, 6.52%, and 0.98% (p = 0.12), and distance recurrences occurred in 16.67%, 8.70%, and 7.84% (p = 0.27), respectively. Time to first recurrence did not differ by SN count (p = 0.41). After adjustment for age, race, clinical stage, and receptor status, there were no differences in the rates of axillary (p = 0.26), breast (p = 0.44), or distance recurrence (p = 0.24) by numbers of SNs harvested. Median follow-up was 46.8 months. Despite higher post-NACT FNRs reported in randomized trials for patients having <3 sentinel nodes, recurrence rates were not significantly different for 1 versus 2 versus ≥3 SNs. This suggests that patients having 1 or 2 post-NACT SNs identified may not necessitate axillary dissection.

Feasibility of Fitness Tracker Usage to Assess Activity Level and Toxicities in Patients With Colorectal Cancer.

PURPOSE: Performance status (PS) is a subjective assessment of patients' overall health. Quantification of physical activity using a wearable tracker (Fitbit Charge [FC]) may provide an objective measure of patient's overall PS and treatment tolerance. MATERIALS AND METHODS: Patients with colorectal cancer were prospectively enrolled into two cohorts (medical and surgical) and asked to wear FC for 4 days at baseline (start of new chemotherapy [± 4 weeks] or prior to curative resection) and follow-up (4 weeks [± 2 weeks] after initial assessment in medical and postoperative discharge in surgical cohort). Primary end point was feasibility, defined as 75% of patients wearing FC for at least 12 hours/d, 3 of 4 assigned days. Mean steps per day (SPD) were correlated with toxicities of interest (postoperative complication or ≥ grade 3 toxicity). A cutoff of 5,000 SPD was selected to compare outcomes. RESULTS: Eighty patients were accrued over 3 years with 55% males and a median age of 59.5 years. Feasibility end point was met with 68 patients (85%) wearing FC more than predefined duration and majority (91%) finding its use acceptable. The mean SPD count for patients with PS 0 was 6,313, and for those with PS 1, it was 2,925 (122 and 54 active minutes, respectively) (P = .0003). Occurrence of toxicity of interest was lower among patients with SPD > 5,000 (7 of 33, 21%) compared with those with SPD < 5,000 (14 of 43, 32%), although not significant (P = .31). CONCLUSION: Assessment of physical activity with FC is feasible in patients with colorectal cancer and well-accepted. SPD may serve as an adjunct to PS assessment and a possible tool to help predict toxicities, regardless of type of therapy. Future studies incorporating FC can standardize patient assessment and help identify vulnerable population.

A novel surgeon credentialing and quality assurance process using transoral surgery for oropharyngeal cancer in ECOG-ACRIN Cancer Research Group Trial E3311.

PURPOSE: Understanding the role of transoral surgery in oropharyngeal cancer (OPC) requires prospective, randomized multi-institutional data. Meticulous evaluation of surgeon expertise and surgical quality assurance (QA) will be critical to the validity of such trials. We describe a novel surgeon credentialing and QA process developed to support the ECOG-ACRIN Cancer Research Group E3311 (E3311) and report outcomes related to QA. PATIENTS AND METHODS: E3311 was a phase II randomized clinical trial of transoral surgery followed by low- or standard-dose, risk-adjusted post-operative therapy with stage III-IVa (AJCC 7th edition) HPV-associated OPC. In order to be credentialed to accrue to this trial, surgeons were required to demonstrate active hospital credentials and technique-specific surgical expertise with ≥20 cases of transoral resection for OPC. In addition, 10 paired operative and surgical pathology reports from the preceding 24 months were reviewed by an expert panel. Ongoing QA required <10% rate of positive margins, low oropharyngeal bleeding rates, and accrual of at least one patient per 12 months. Otherwise surgeons were placed on hold and not permitted to accrue until re-credentialed using a new series of transoral resections. RESULTS: 120 surgeons trained in transoral minimally invasive surgery applied for credentialing for E3311 and after peer-review, 87 (73%) were approved from 59 centers. During QA on E3311, positive final pathologic margins were reported in 19 (3.8%) patients. Grade III/IV and grade V oropharyngeal bleeding was reported in 29 (5.9%) and 1 (0.2%) of patients. CONCLUSIONS: We provide proof of concept that a comprehensive credentialing process can support multicenter transoral head and neck surgical oncology trials, with low incidence of positive margins and *grade III/V oropharyngeal bleeding.

Treatment times in breast cancer patients receiving neoadjuvant vs adjuvant chemotherapy: Is efficiency a benefit of preoperative chemotherapy?

BACKGROUND/OBJECTIVE: Delays in times to surgery, chemotherapy, and radiotherapy impair survival in breast cancer patients. Neoadjuvant chemotherapy (NAC) confers equivalent survival to adjuvant chemotherapy (AC), but it remains unknown which approach facilitates faster initiation and completion of treatment. METHODS: Women ≥18 years old with nonrecurrent, noninflammatory, clinical stage I-III breast cancer diagnosed between 2004 and 2015 who underwent both surgery and chemotherapy were reviewed from the National Cancer Database. RESULTS: Among 155 606 women overall, 28 241 patients received NAC and 127 365 patients received AC. NAC patients had higher clinical T and N stages (35.8% T3/4 vs 4.9% T3/4; 14.4% N2/3 vs 3.7% N2/3). After adjusting for stage and other factors, NAC patients had longer times to begin treatment (36.1 vs 35.4 days adjusted, P = .15), and took significantly longer to start radiotherapy (240.8 vs 218.2 days adjusted, P < .0001), and endocrine therapy (301.6 vs 275.7 days adjusted, P < .0001). Unplanned readmissions (1.2% vs 1.7%), 30-day mortality (0.04% vs 0.01%), and 90-day mortality (0.30% vs 0.08%) were all low and clinically insignificant between NAC and AC. CONCLUSION: Compared to patients receiving AC, those receiving NAC do not start treatment sooner. In addition, patients receiving NAC do not complete treatment faster. Although there are clear indications for administering NAC vs AC, rapidity of treatment should not be considered a benefit of giving chemotherapy preoperatively.

Preoperative Delays in the Treatment of DCIS and the Associated Incidence of Invasive Breast Cancer.

BACKGROUND: Although treatment delays have been associated with survival impairment for invasive breast cancer, this has not been thoroughly investigated for ductal carcinoma in situ (DCIS). With trials underway to assess whether DCIS can remain unresected, this study was performed to determine whether longer times to surgery are associated with survival impairment or increased invasion. METHODS: A population-based study of prospectively collected national data derived from women with a clinical diagnosis of DCIS between 2004 and 2014 was conducted using the National Cancer Database. Overall survival (OS) and presence of invasion were assessed as functions of time by evaluating five intervals (≤ 30, 31-60, 61-90, 91-120, 121-365 days) between diagnosis and surgery. Subset analyses assessed those having pathologic DCIS versus invasive cancer on final pathology. RESULTS: Among 140,615 clinical DCIS patients, 123,947 had pathologic diagnosis of DCIS and 16,668 had invasive ductal carcinoma. For all patients, 5-year OS was 95.8% and unadjusted median delay from diagnosis to surgery was 38 days. With each delay interval increase, added relative risk of death was 7.4% (HR 1.07; 95% CI 1.05-1.10; P < 0.001). On final pathology, 5-year OS for noninvasive patients was 96.0% (95% CI 95.9-96.1%) versus 94.9% (95% CI 94.6-95.3%) for invasive patients. Increasing delay to surgery was an independent predictor of invasion (OR 1.13; 95% CI 1.11-1.15; P < 0.001). CONCLUSIONS: Despite excellent OS for invasive and noninvasive cohorts, invasion was seen more frequently as delay increased. This suggests that DCIS trials evaluating nonoperative management, which represents infinite delay, require long term follow up to ensure outcomes are not compromised.

Intergroup Randomized Phase III Study of Postoperative Oxaliplatin, 5-Fluorouracil, and Leucovorin Versus Oxaliplatin, 5-Fluorouracil, Leucovorin, and Bevacizumab for Patients with Stage II or III Rectal Cancer Receiving Preoperative Chemoradiation: A Trial of the ECOG-ACRIN Research Group (E5204).

BACKGROUND: The addition of bevacizumab to chemotherapy improved outcomes for patients with metastatic colon cancer. E5204 was designed to test whether the addition of bevacizumab to mFOLFOX6, following neoadjuvant chemoradiation and definitive surgery, could improve overall survival (OS) in patients with stage II/III adenocarcinoma of the rectum. SUBJECTS, MATERIALS, AND METHODS: Patients with stage II/III rectal cancer who had completed neoadjuvant 5-fluorouracil-based chemoradiation and had undergone complete resection were enrolled. Patients were randomized to mFOLFOX6 (Arm A) or mFOLFOX6 with bevacizumab (Arm B) administered every 2 weeks for 12 cycles. RESULTS: E5204 registered only 355 patients (17% of planned accrual goal) as it was terminated prematurely owing to poor accrual. At a median follow-up of 72 months, there was no difference in 5-year overall survival (88.3% vs. 83.7%) or 5-year disease-free survival (71.2% vs. 76.5%) between the two arms. The rate of treatment-related grade ≥ 3 adverse events (AEs) was 68.8% on Arm A and 70.7% on Arm B. Arm B had a higher proportion of patients who discontinued therapy early as a result of AEs and patient withdrawal than did Arm A (32.4% vs. 21.5%, p = .029).The most common grade 3-4 treatment-related AEs were neutropenia, leukopenia, neuropathy, diarrhea (without prior colostomy), and fatigue. CONCLUSION: At 17% of its planned accrual, E5204 did not meet its primary endpoint. The addition of bevacizumab to FOLFOX6 in the adjuvant setting did not significantly improve OS in patients with stage II/III rectal cancer. IMPLICATIONS FOR PRACTICE: At 17% of its planned accrual, E5204 was terminated early owing to poor accrual. At a median follow-up of 72 months, there was no significant difference in 5-year overall survival (88.3% vs. 83.7%) or in 5-year disease-free survival (71.2% vs. 76.5%) between the two arms. Despite significant advances in the treatment of rectal cancer, especially in improving local control rates, the risk of distant metastases and the need to further improve quality of life remain a challenge. Strategies combining novel agents with chemoradiation to improve both distant and local control are needed.

Time to Surgery and the Impact of Delay in the Non-Neoadjuvant Setting on Triple-Negative Breast Cancers and Other Phenotypes.

BACKGROUND: Characterization of breast cancer phenotypes has improved our ability to predict breast cancer behavior. Triple-negative (TN) breast cancers have higher and earlier rates of distant events. It has been suggested that this behavior necessitates treating TNs faster than others, including use of neoadjuvant chemotherapy (NACT) if time to surgery is not rapid. METHODS: A review of women diagnosed with non-inflammatory, invasive breast cancer was conducted using the National Cancer Database for patients not having NACT, diagnosed between 2010 and 2014. Changes in overall survival due to delay were measured by phenotype. RESULTS: Overall, 351,087 patients met the inclusion criteria, including 36,505 (10.4%) TNs, 77.9% hormone receptor-positive (HR+) and 11.7% human epidermal growth factor receptor 2 (HER2)-enriched (HER2+). Phenotype, among other factors, was predictive of treatment delays. Adjusted median days from diagnosis to surgery and chemotherapy were 29.9, 31.6 and 31.5 (p< 0.001), and 72.7, 78.0 and 74.4 (p< 0.001) for TNs, HR+ and HER2+ cancers, respectively. After diagnosis, OS declined for all patients per month of preoperative delay (hazard ratio 1.104; p< 0.001). In models separating or combining surgery and chemotherapy, this survival decline did not vary by breast cancer phenotype (p > 0.3). CONCLUSIONS: Delays cause small but measurable effects overall, but the effect on survival does not differ among breast cancer phenotypes. Our data suggest that urgency between diagnosis and surgery or chemotherapy is similar for breast cancers of different subtypes. Although NACT is sometimes advocated solely to avoid treatment delays, this study does not suggest a greater surgical urgency for TNs compared with other breast cancer phenotypes.

Impact of PET/CT for Restaging Patients With Locally Advanced Rectal Cancer After Neoadjuvant Chemoradiation.

BACKGROUND: A major challenge in identifying candidates for nonoperative management of locally advanced rectal cancer is predicting pathologic complete response (pCR) following chemoradiation. We evaluated pre- and post-CRT PET-CT imaging to predict pCR and prognosis in this set of patients undergoing resection after neoadjuvant therapy. METHODS: We retrospectively identified patients from 2002 to 2015 with locally advanced rectal cancer who underwent CRT, pre- and post-CRT PET-CT imaging, and resection. Univariate and multivariate analysis was performed and receiver operating characteristic (ROC) curves were generated to evaluate the association of PET-CT characteristics with pCR and survival. ROC curves were generated to define optimal cutoff points for predictive PET-CT characteristics. RESULTS: 125 patients were included. pCR rate was 28%, and follow-up was 48 mo. On multivariable analysis, patients who had a pCR had lower median post-CRT maximal standardized uptake value (SUVmax) (3.2 versus 5.2, P = 0.009) and higher median %SUV decrease (72 versus 58%, P = 0.009). ROC curves were generated for %SUVmax decrease (AUC = 0.70) and post-CRT SUV (AUC = 0.69). Post-CRT SUVmax <4.3 and %SUVmax decrease of >66% were equally predictive of pCR with a sensitivity of 65%, specificity of 72%, PPV of 44%, and NPV of 86%. Median 5-y overall and relapse-free survival were improved for patients with post-CRT SUV <4.3 (OS: 86 versus 66%, P = 0.01; RFS: 75 versus 52%, P = 0.01) or %SUV decrease of >66% (OS, 82 versus 66%, P = 0.05; RFS, 75 versus 54%, P = 0.01). CONCLUSIONS: PET/CT may be useful in identifying patients who did not achieve pCR, as well as overall survival in patients undergoing CRT for rectal cancer. Patients with a post-CRT SUV of >4.3 should be considered for operative management, as an estimated 86% of these patients will not have a pCR.

Patterns of Care and Efficacy of Chemotherapy and Radiotherapy in Skin-Involved Breast Cancers of All Sizes.

BACKGROUND: The management of small skin-involved (SI) invasive breast cancers is controversial because although they are considered unresectable, their prognosis is far better than their stage III classification. This study was undertaken to determine how SI lesions are treated in the United States and to discern the benefit of systemic therapy. PATIENTS AND METHODS: Data of patients diagnosed with stage I-III breast cancer in the National Cancer Data Base between 2004 and 2011 were reviewed. Treatment patterns were examined and overall survival assessed. RESULTS: A total of 3485 patients had SI and 456,287 patients had non-SI breast cancers. Chemotherapy was administered to 68.5% of SI and 45.9% of non-SI tumors (P < .001), including 77.2% of SI and 33% of non-SI tumors < 2 cm (P < .001). After adjusting for patient and tumor characteristics, SI patients were 19.4% more likely to receive chemotherapy than non-SI patients. Radiotherapy was provided to 61.1% of SI and 64.3% of non-SI tumors (P < .001), including 65.5% of SI and 66.5% non-SI tumors < 2 cm (P = .711). After adjusting for patient and tumor characteristics, SI patients were 76.6% more likely to receive radiotherapy than non-SI patients. Chemotherapy and radiotherapy provided an overall survival benefit for stage II and III SI and non-SI tumors. CONCLUSION: Despite controversy regarding staging and prognosis of SI tumors, the majority of patients are provided systemic therapy and radiotherapy. Varied patterns of chemotherapy administration for SI tumors suggests that further treatment guidance and standardization are required, especially because chemotherapy and radiotherapy are equally efficacious in SI and non-SI tumors alike.

Breast conservation versus mastectomy in patients with T3 breast cancers (> 5 cm): an analysis of 37,268 patients from the National Cancer Database.

PURPOSE: Breast conservation therapy (BCT) is standard for T1-T2 tumors, but early trials excluded breast cancers > 5 cm. This study was performed to assess patterns and outcomes of BCT for T3 tumors. METHODS: We reviewed the National Cancer Database (NCDB) for noninflammatory breast cancers > 5 cm, between 2004 and 2011 who underwent BCT or mastectomy (Mtx) with nodal evaluation. Patients with skin or chest wall involvement were excluded. Patients having clinical T3 tumors were analyzed to determine outcomes based upon presentation, with those having pathologic T3 tumors, subsequently assessed, irrespective of presentation. Overall survival (OS) was analyzed using multivariable Cox proportional hazards models, with adjusted survival curves estimated using inverse probability weighting. RESULTS: After exclusions, 37,268 patients remained. Median age and tumor size for BCT versus Mtx were 53 versus 54 years (p < 0.001) and 6.0 versus 6.7 cm (p < 0.001), respectively. Predictors of BCT included age, race, location, facility type, year of diagnosis, tumor size, grade, histology, nodes examined and positive, and administration of chemotherapy and radiotherapy. OS was similar between Mtx and BCT (p = 0.36). This held true when neoadjuvant chemotherapy patients were excluded (p = 0.39). BCT percentages declined over time (p < 0.001), while tumor sizes remained the same (p = 0.77). Median follow-up was 51.4 months. CONCLUSIONS: OS for patients with T3 breast cancers is similar whether patients received Mtx or BCT, confirming that tumor size should not be an absolute BCT exclusion. Declining use of BCT for tumors > 5 cm in younger patients may be accounted for by recent trends toward mastectomy.