Modified Docetaxel, Cisplatin, and Fluorouracil (mDCF) as a Neoadjuvant Chemotherapy for Non-metastatic Esophageal Cancer (nMEC).

Objective: Perioperative chemotherapy can potentially downstage esophageal cancer, reducing the risk of early systemic dissemination. One recommended neoadjuvant regimen for managing gastroesophageal junction and esophageal cancer is docetaxel, cisplatin, and 5-fluorouracil (DCF). To address the high toxicity profile of DCF, modifications in dosages and treatment intervals have been studied. We integrated a modified DCF regimen (mDCF) into a multimodal treatment approach for non-metastatic esophageal cancer (nMEC). Retrospectively, we sought to describe our community experience of administrating neoadjuvant mDCF to patients with nMEC.Design: Patients diagnosed with nMEC between August 2008 and November 2017 and prescribed mDCF were identified for retrospective review. Outcomes of interest included disease-free survival (DFS), overall survival (OS), and hematologic toxicities. Analyses were performed using SAS 9.4.Results: Thirty patients met inclusion criteria with a median age of 64.9 years; 90% were male. The 2-year and 5-year DFS was 60.8% and 41.7%, respectively, for adenocarcinoma and 71.4% and 71.4% for squamous cell carcinoma (SCC). The 2-year and 5-year OS was 64.9% and 44.5%, respectively, for adenocarcinoma and 71.4% and 71.4% for SCC. Both DFS and OS decreased with increasing disease stage, histology (adenocarcinoma versus squamous), esophageal compared to esophagogastric-junction involvement, and without surgical intervention. Frequent toxicity grades for leukopenia and thrombocytopenia were Grades I and II.Conclusion: Using an mDCF regimen in combination with chemoradiation +/- surgical resection in a community setting appears to have an acceptable toxicity profile as well as DFS and OS outcomes compared to chemotherapeutic regimens reported in other similar studies.

Breast Cancer Outcomes of Neoadjuvant Versus Adjuvant Chemotherapy by Receptor Subtype: A Scoping Review.

BACKGROUND: Trials demonstrate equivalent survival for breast cancers treated with neoadjuvant chemotherapy (NAC) or adjuvant chemotherapy (AC). However, these were conducted before the recognition of the importance of receptor subtype for survival and chemotherapy response. Therefore, chemotherapy timing may impact survival for certain receptor subtypes. A scoping review of studies assessing outcomes by chemotherapy timing based on receptor subtype was conducted to evaluate gaps in the existing literature. METHODS: Three databases were searched in February 2019 with terms related to breast cancer, NAC/AC, and survival. Inclusion criteria were original peer-reviewed studies published in English after 1989 comparing breast cancer outcomes for females based on chemotherapy timing. Studies/sections of studies lacking outcomes by receptor subtype or including patients missing appropriate targeted therapy were excluded. RESULTS: Of 7354 articles, 262 abstracts and 60 full texts were reviewed. Three studies met criteria. All were single-institution retrospective studies analyzing outcomes for triple negative (TN) patients with one study also examining luminal A patients. Significant differences in clinical characteristics existed between patients selected for NAC versus AC. Two studies demonstrated no survival difference by chemotherapy timing for TN patients, with the third showing improved likelihood of survival after AC for TN patients. No difference was seen for patients with luminal A cancer. CONCLUSIONS: Our scoping review reveals a significant gap in the existing literature regarding optimal timing of chemotherapy for modern-era patients receiving targeted therapy based on receptor subtype. Review of the identified studies identified methodological challenges to answering this question through observational study designs.

Management of the Axilla after Neoadjuvant Systemic Therapy.

OPINION STATEMENT: As the use of neoadjuvant systemic therapy (NAST) increases, the optimal management of the axilla has become increasingly complex. Consensus among professional organizations is that those patients with clinically negative axillary nodes who are being considered for NAST should undergo a sentinel lymph node (SLN) biopsy following NAST. If a positive SLN is subsequently identified, an axillary lymph node dissection (ALND) is the current standard of care. For patients with clinically node-positive disease, SLN biopsy is a reasonable option for those with a good response to NAST. Patients should undergo SLN mapping with a dual dye technique. Additionally, at least 2 lymph nodes should be removed, including the previously biopsied and marked lymph node with cancer. In this setting, the identification and false negative rates are acceptable. Patients found to have a negative SLN at this time may be spared the morbidity associated with ALND. Patients found to have persistently positive lymph nodes following NAST, either clinically or pathologically, should undergo a complete ALND.

Time to initiation of neo-adjuvant chemotherapy for breast cancer treatment does not influence patient survival: A study of US breast cancer patients.

Delays in the initiation of adjuvant chemotherapy or radiation therapy are associated with worse outcomes in patients undergoing treatment for breast cancer. However, the impact of the time to initiation of neo-adjuvant chemotherapy (NAC) on patient outcomes has not previously been studied. The purpose of this study was to determine whether delays in NAC initiation impact patient survival. The National Cancer Database was queried for women ≥ 18 years old who underwent NAC within 6 months of being diagnosed with stage I-III invasive breast cancer in 2010-2011. ER+ or PR+, Her2- cancers were excluded from analysis. Multivariable Cox proportional hazard modeling was used to evaluate the relationship between time to NAC, sociodemographic, diagnosis, and treatment factors with patient survival. The median age of the 12 806 women included in this study was 52 (range 21-90) with 62% presenting with cT2 disease and 62% with nodal involvement. Half of the women (50%) had triple negative, 30% ER/PR+Her2+ and 20% ER-PR-Her2+ cancers. The median time to starting NAC was 4 weeks (range 0-26) for all subtypes. Time to NAC initiation was not associated with a difference in survival for triple negative or Her2+ cancers. Delays from diagnosis to starting NAC are not associated with worse survival for patients with Her2+ or triple negative breast cancer. This study demonstrates that the majority of women in the modern era start NAC in a timely fashion and delays in starting NAC within 6 months of diagnosis do not impact long-term patient outcomes.

Breast Cancer Found Incidentally After Reduction Mammaplasty in Young Insured Women.

BACKGROUND: Reduction mammaplasty is a common operation performed for healthy women. The estimated incidence of breast cancer diagnosed at the time of reduction mammaplasty varies from 0.06 to 4.5%, and information on the care of these patients is limited. This study aimed to determine the incidence of breast cancer identified incidentally during reduction mammaplasty and to characterize preoperative imaging. METHODS: Women 18 years of age or older who underwent reduction mammaplasty from 2013 to 2015 were identified from the Truven Health MarketScan® Research Databases. Patients with prior breast cancer were excluded. Descriptive statistics were calculated for patient characteristics, incidental breast cancer, preoperative breast imaging, and postoperative treatment. RESULTS: Reduction mammaplasty was performed for 18,969 women with a mean age of 42.5 years. Of these patients, 186 (0.98%) were incidentally found to have breast cancer, with 134 (0.71%) having invasive breast cancer and 52 (0.27%) having carcinoma in situ. The patients with incidentally found cancer were older than the patients without cancer (50.8 vs. 42.5 years; p < 0.001). Overall, 58.2% of the patients had undergone mammography before reduction mammoplasty. The rates were higher (> 80%) for the patients older than 40 years. Preoperative mammography was performed for 76.3% of those with a diagnosis of breast cancer at time of reduction mammoplasty. CONCLUSIONS: Breast cancer diagnosed incidentally at the time of reduction mammaplasty is uncommon and often radiographically occult. The majority of women older than 50 years appropriately received preoperative mammography. These data can be used to manage patient expectations about the potential for the incidental diagnosis of breast cancer at reduction mammaplasty, even with a negative preoperative mammography.

A Randomized Controlled Trial Evaluating the Impact of Pre-Consultation Information on Patients' Perception of Information Conveyed and Satisfaction with the Decision-Making Process.

BACKGROUND: Patient participation in treatment decision-making is a health care priority. This study hypothesized that providing a decision aid before surgical consultation would better prepare patients for decision-making. The objective was to examine the impact of a decision aid versus high-quality websites on patients' perceptions of information conveyed during surgical consultation and satisfaction with the decision process. METHODS: Patients with stages 0 to 3 breast cancer were randomized. Surveys assessed perceptions of information conveyed, being asked surgical preference, and satisfaction with the decision process. Multivariable logistic regression assessed associations between outcomes and randomization arm, patient factors, and surgeon. Change in Pseudo-R2 assessed the comparative effect of these factors on perceptions of the information conveyed. RESULTS: The median patient age was 59 years. Most of the patients (98%) were white, and 62% were college educated (n = 201). The findings showed no association between randomization arm and perceptions of information conveyed, being asked surgical preference, or satisfaction with the decision process. Most of the patients reported discussing both breast-conserving therapy and mastectomy (69%) and being asked their surgical preference (65%). The surgeon seen was more important than the randomization arm or the patient factors in predicting patients' perceptions of information conveyed (explained 64-69% of the variation), and 63% of the patients were satisfied with the decision process. CONCLUSION: Use of a decision aid compared with high-quality websites did not increase patients' perceptions of information conveyed or satisfaction with the decision process. Although the surgeon seen influenced aspects of the patient experience, the surgeon was not associated with satisfaction. Understanding the factors driving low satisfaction is critical because this is increasingly used as a marker of health care quality.

All-cause mortality is decreased in women undergoing annual mammography before breast cancer diagnosis.

OBJECTIVE: The value of annual mammography remains an area of debate because of concerns regarding risk versus benefit. The potential for harm due to overdiagnosis and treatment of clinically insignificant cancers may not be captured by breast cancer-specific mortality. Instead, we examined all-cause mortality as a function of missed annual mammography examinations before breast cancer diagnosis. MATERIALS AND METHODS: Primary breast cancer cases diagnosed in the Marsh-field Clinic Health System from 2002 through 2008 were identified for retrospective review, and whether annual mammography examinations had been performed in the 5 years before diagnosis was assessed. RESULTS: Analyses were performed on 1421 women with breast cancer. After adjustment of data for age, comorbidity status, a family history of breast cancer, insurance status, medical encounter frequency, and the calendar year, women who had missed any of the previous five annual mammography examinations had a 2.3-fold increased risk of all-cause mortality compared with subjects with no missed mammography examinations (hazard ratio=2.28; 95% CI, 1.58-3.30; p<0.0001). Additionally, an analysis by the number of missed annual mammography examinations showed a progressive increase in hazard as the number of missed mammography studies increased. CONCLUSION: These results suggest that annual mammography before breast cancer diagnosis is predictive of increased overall survival. A stepwise decline in overall survival was noted for each additional missed mammography examination. These results are similar to findings in the literature for breast cancer-specific mortality and illustrate the importance of recommending annual mammography to all eligible women.

Rates of Ipsilateral Local-regional Recurrence in High-risk Patients Undergoing Immediate Post-mastectomy Reconstruction (AFT-01).

BACKGROUND: Some surgeons remain hesitant to perform immediate breast reconstruction (IBR) in patients with higher risk cancers owing to concerns about cancer recurrence and/or detection. Our objective was to determine the rate of ipsilateral local-regional recurrence for stage II/III patients who underwent IBR. METHODS: The National Cancer Database special study mechanism was used to create a stratified sample of women diagnosed with stage II/III breast cancer from 1217 facilities. Demographic, tumor, and recurrence data for women who underwent mastectomy with or without IBR were abstracted, including location of recurrence and method of detection. Estimates of 5-year local-regional recurrence rates were calculated and factors associated with recurrence were identified with multivariable Cox regression. RESULTS: Some 13% (692/5318) of stage II/III patients underwent IBR after mastectomy. Patients undergoing IBR were younger (P < .001), with fewer comorbid conditions (P < .001), and with lower tumor burden in the breast (P = .001) and the lymph nodes (P = 0.01). The 5-year rate of ipsilateral local-regional recurrence was 3.6% with no significant difference between patients with or without IBR (3.0% vs. 3.7%, P = .4). Most recurrences were detected by the patient (45%) or on physician examination (24%). Reconstruction was not associated with recurrence on multivariable analysis (hazard ratio = 0.83, P = .52). CONCLUSION: Women with stage II/III breast cancer selected for IBR had similar rates of ipsilateral local-regional recurrence compared with those undergoing mastectomy alone. Offering IBR after mastectomy in a patient-centered manner to select patients with stage II/III breast cancer is an acceptable consideration.

Serum immunoglobulin free light chain measurements and heavy chain isotype usage provide insight into disease biology in patients with POEMS syndrome.

POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes) syndrome is a rare paraneoplastic syndrome in which nearly all patients have a monoclonal lambda restricted plasma cell disorder. We investigated whether patients with POEMS have abnormal serum immunoglobulin free light chain (FLC) ratios. Fifty patients with newly diagnosed POEMS syndrome were assessed. Cystatin C levels were measured to discern whether subclinical renal insufficiency could account for FLC elevations in the presence of a normal FLC ratio. Forty-five patients (90%) had elevated lambda FLC; however, only nine (18%) had abnormal FLC ratios. The rise in serum FLC of POEMS patients appeared to be multifactorial-both a function of subclinical renal insufficiency and polyclonal activation of medullary and extramedullary plasma cells. Those patients expressing a clonal IgA were more likely to have clonal plasmacytosis observed on iliac crest biopsy than those with IgG. In summary, serum immunoglobulin profiles are unique in POEMS syndrome as compared with other plasma cell disorders.

Does Tumor Size Predict Response to Neoadjuvant Chemotherapy in the Modern Era of Biologically Driven Treatment? A Nationwide Study of US Breast Cancer Patients.

BACKGROUND: Tumor size has historically been used to stage breast cancer and guide treatment recommendations. The importance of tumor biology in long-term outcomes is increasingly being acknowledged. No large studies have examined the relative roles of tumor size and receptor status on response to neoadjuvant chemotherapy (NAC) in breast cancer. PATIENTS AND METHODS: The National Cancer Database was queried for women who underwent NAC and surgery for unilateral clinical stage I to III (cT1-3) invasive breast cancer from 2010 to 2013. Multivariable logistic regression models were used to assess the relation between receptor status, tumor size, and pathologic complete response (pCR) while controlling for other biologic, sociodemographic, diagnosis, and treatment factors. RESULTS: We included 38,864 women in this study, most presented with cT2 disease (55%). Patients predominantly had estrogen receptor (ER)/progesterone receptor (PR)-positive (ER/PR+) HER2- (45%) or ER/PR- HER2- (28%) disease. Nineteen percent (7432 patients) had a pCR. cT3 (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.59-0.70) but not cT2 cancers (OR, 0.95; 95% CI, 0.89-1.02) were associated with lower pCR rates compared with cT1 disease. HER2+ (ER/PR+ HER2+: OR, 2.94; 95% CI, 2.72-3.18; ER/PR- HER2+: OR, 6.45; 95% CI, 5.92-7.02) and ER/PR- HER2- cancers (OR, 3.94; 95% CI, 3.68-4.22) were more likely to experience pCR than those with ER/PR+ HER2- cancers. Receptor status was more strongly associated with pCR than tumor size. CONCLUSION: Tumor size is independently associated with pCR after NAC after controlling for receptor status, although the effect of receptor status is stronger. These data reinforce the importance of receptor status as well as tumor size, each of which might act as surrogates for tumor biology, in setting expectations for outcomes in patients who undergo NAC.

Cancer Care Delivery Research: A Path to Improving the Quality of Oncologic Surgical Care.

The goal of cancer care delivery research (CCDR) is to inform sustainable practice changes that will provide better clinical outcomes and patient experience guided by patient values. CCDR encompasses salient concepts from other well-established research approaches and spans the continuum of research from hypothesis generation to effectiveness studies to policy development. CCDR incorporates pertinent attributes, such as saliency to stakeholders, inclusion of diverse participants, and implementation into real-world settings. This article provides examples of CCDR studies, focusing specifically on how CCDR can improve the quality of oncologic surgical care.