Impact of anesthesia technique on post-operative opioid use in open gynecologic surgery in an enhanced recovery after surgery pathway.

Objective: To examine the effect of anesthesia technique in an enhanced recovery after surgery (ERAS) pathway on post-operative opioid use.

Methods: Patients undergoing open gynecologic surgery under an ERAS pathway from November 2014 through December 2018 were included retrospectively. All patients received pre-operative analgesia consisting of oral acetaminophen, pregabalin, celecoxib, and tramadol extended release, unless contraindicated.

Biomarkers for Risk Stratification in Patients With Previously Untreated Follicular Lymphoma Receiving Anti-CD20-based Biological Therapy.

Follicular lymphoma (FL) is an indolent B-cell neoplasm of germinal center origin. Standard treatment regimens consist of anti-CD20 therapy with or without chemotherapy. While high response rates to initial therapy are common, patients ultimately relapse or have progressive disease.

Enhanced recovery for obese patients undergoing gynecologic cancer surgery.

Objective: To compare post-operative length of stay and complication rates of matched obese and non-obese patients in an enhanced recovery (ERAS) program after open gynecologic cancer surgery.

Methods: We performed an observational cohort study of patients (n=1225) undergoing open surgery from November 2014 to November 2018 at a tertiary cancer center. Patients undergoing multidisciplinary procedures, non-oncologic surgery, or procedures in addition to abdominal surgery were excluded (n=190).

A prospective randomized trial comparing liposomal bupivacaine vs standard bupivacaine wound infiltration in open gynecologic surgery on an enhanced recovery pathway.

Background: Value in healthcare is reflected by patient-centered outcomes of care per health dollar expended. Although liposomal bupivacaine is more expensive, it has been shown to provide prolonged analgesia (up to 72 hours).

Objective: This study aimed to evaluate whether the addition of liposomal bupivacaine to standard bupivacaine could decrease opioid intake and improve pain control after laparotomy for gynecologic surgery compared with standard bupivacaine alone in an enhanced recovery after surgery pathway.

Longitudinal Toxicity over Time (ToxT) analysis to evaluate tolerability: a case study of lenalidomide in the CALGB 50401 (Alliance) trial.

Evaluation of tolerability is increasingly relevant for patients with haematological malignancies treated with chronically administered therapies. Adverse events from these agents might affect the ability of patients to tolerate treatment over time. Conventional toxicity tables that include the incidence of high-grade adverse events, defined by the Common Terminology Criteria for Adverse Events, do not provide information on the time profile of these adverse events or reflect the continuous, lower grade symptomatic toxicities that are particularly relevant to treatment tolerability for patients living with indolent disease.

Impact of compliance with an enhanced recovery after surgery pathway on patient outcomes in open gynecologic surgery.

Objective: The aim of this study was to evaluate if varying levels of compliance with an enhanced recovery after surgery (ERAS) protocol impacted post-operative outcomes (length of stay, complications, readmissions, and re-operations) in gynecologic surgery at a tertiary center.

Methods: We included 584 patients who had open gynecologic surgery between November 1, 2014 and December 31, 2016. Patients were categorized into subgroups according to their date of surgery from the time of the ERAS protocol implementation.

Impact of implementation of an enhanced recovery program in gynecologic surgery on healthcare costs.

Background: Enhanced recovery programs have been associated with improved outcomes after gynecologic surgery. There are limited data on the effect of enhanced recovery programs on healthcare costs or healthcare service use.

Objective: The purpose of this study was to evaluate differences in hospital charges for women who undergo surgery for a suspected gynecologic cancer that is managed in an enhanced recovery program as compared with conventional perioperative care.

Dose-Adjusted EPOCH-R Compared With R-CHOP as Frontline Therapy for Diffuse Large B-Cell Lymphoma: Clinical Outcomes of the Phase III Intergroup Trial Alliance/CALGB 50303.

Purpose: Alliance/CALGB 50303 (NCT00118209), an intergroup, phase III study, compared dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) with standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as frontline therapy for diffuse large B-cell lymphoma.

Patients And Methods: Patients received six cycles of DA-EPOCH-R or R-CHOP. The primary objective was progression-free survival (PFS); secondary clinical objectives included response rate, overall survival (OS), and safety.

Phase 2 multicentre study of single-agent ofatumumab in previously untreated follicular lymphoma: CALGB 50901 (Alliance).

Rituximab monotherapy has proven efficacy in treatment-naïve, asymptomatic advanced-stage follicular lymphoma (FL). Ofatumumab is a fully humanized anti-CD20 monoclonal antibody with increased CD20 affinity and complement-dependent cytotoxicity. This phase 2 trial (NCT01190449) evaluated ofatumumab in patients with untreated, low/intermediate-risk FL International Prognostic Index (FLIPI), advanced-stage FL to determine single-agent efficacy.

The prognostic significance of PFS24 in follicular lymphoma following firstline immunotherapy: A combined analysis of 3 CALGB trials.

Follicular lymphoma (FL) patients treated with firstline R-CHOP who experience progression of disease (POD) within 2 years have a shorter survival than those who do not have POD within 2 years. Whether this observation holds for patients treated initially with biologic immunotherapy alone is unknown. We performed a retrospective analysis of 174 patients pooled from three frontline rituximab (R)-based nonchemotherapy doublet trials: R-galiximab (Anti-CD80, CALGB 50402), R-epratuzumab (Anti-CD22, CALGB 50701), and R-lenalidomide (CALGB 50803) to determine outcomes of early progressors and risk factors for early POD, defined as progression within 24 months from study entry.

Perineural invasion (PNI) in vulvar carcinoma: A review of 421 cases.

Objectives: To evaluate the prevalence and associated prognostic indicators in patients with vulvar carcinoma with and without evidence of perineural invasion (PNI).

Methods: A retrospective review identified 421 patients with invasive vulvar carcinoma evaluated at a single institution between 1993 and 2011. Medical records were reviewed for demographic data, pathologic information and presence or absence of PNI, treatment type, and recurrence/outcome information.

CALGB 50604: risk-adapted treatment of nonbulky early-stage Hodgkin lymphoma based on interim PET.

A negative interim positron emission tomography/computerized tomography (PET/CT) after 1 to 3 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in patients with newly diagnosed, nonbulky stage I or II Hodgkin lymphoma (HL) predicts a low relapse rate. This phase 2 trial was designed to determine if a population of patients with early-stage disease can be treated with short-course ABVD without radiation therapy (RT) on the basis of a negative interim PET/CT, thereby limiting the risks of treatment. Between 15 May 2010 and 21 February 2013, 164 previously untreated patients with nonbulky stage I/II HL were enrolled, and 149 were included in the final analysis.

Integrated Analysis of RNA and DNA from the Phase III Trial CALGB 40601 Identifies Predictors of Response to Trastuzumab-Based Neoadjuvant Chemotherapy in HER2-Positive Breast Cancer.

Response to a complex trastuzumab-based regimen is affected by multiple features of the tumor and its microenvironment. Developing a predictive algorithm is key to optimizing HER2-targeting therapy. We analyzed 137 pretreatment tumors with mRNA-seq and DNA exome sequencing from CALGB 40601, a neoadjuvant phase III trial of paclitaxel plus trastuzumab with or without lapatinib in stage II to III HER2-positive breast cancer.

Expanded Genomic Profiling of Circulating Tumor Cells in Metastatic Breast Cancer Patients to Assess Biomarker Status and Biology Over Time (CALGB 40502 and CALGB 40503, Alliance).

We profiled circulating tumor cells (CTCs) to study the biology of blood-borne metastasis and to monitor biomarker status in metastatic breast cancer (MBC). CTCs were isolated from 105 patients with MBC using EPCAM-based immunomagnetic enrichment and fluorescence-activated cells sorting (IE/FACS), 28 of whom had serial CTC analysis (74 samples, 2-5 time points). CTCs were subjected to microfluidic-based multiplex QPCR array of 64 cancer-related genes ( = 151) and genome-wide copy-number analysis by array comparative genomic hybridization (aCGH; = 49).

Safety and tolerability of idelalisib, lenalidomide, and rituximab in relapsed and refractory lymphoma: the Alliance for Clinical Trials in Oncology A051201 and A051202 phase 1 trials.

Background: A new generation of biological and targeted agents might potentially replace traditional cytotoxic agents in lymphoma. Lenalidomide plus rituximab was felt to be a safe and promising backbone based on available data. Idelalisib is an oral phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor that has promising activity as a monotherapy in refractory indolent lymphomas.

Using ePrognosis to estimate 2-year all-cause mortality in older women with breast cancer: Cancer and Leukemia Group B (CALGB) 49907 and 369901 (Alliance A151503).

Purpose: Tools to estimate survival, such as ePrognosis ( http://eprognosis.ucsf.edu/carey2.

Phase 1 trial of rituximab, lenalidomide, and ibrutinib in previously untreated follicular lymphoma: Alliance A051103.

Chemoimmunotherapy in follicular lymphoma is associated with significant toxicity. Targeted therapies are being investigated as potentially more efficacious and tolerable alternatives for this multiply-relapsing disease. Based on promising activity with rituximab and lenalidomide in previously untreated follicular lymphoma (overall response rate [ORR] 90%-96%) and ibrutinib in relapsed disease (ORR 30%-55%), the Alliance for Clinical Trials in Oncology conducted a phase 1 trial of rituximab, lenalidomide, and ibrutinib.

Long-term trajectories of self-reported cognitive function in a cohort of older survivors of breast cancer: CALGB 369901 (Alliance).

Background: The number of survivors of breast cancer aged ≥65 years ("older") is growing, but to the authors' knowledge, little is known regarding the cognitive outcomes of these individuals.

Methods: A cohort of cognitively intact older survivors with nonmetastatic, invasive breast cancer was recruited from 78 sites from 2004 through 2011; approximately 83.7% of the survivors (1280 survivors) completed baseline assessments.

PAM50 gene signatures and breast cancer prognosis with adjuvant anthracycline- and taxane-based chemotherapy: correlative analysis of C9741 (Alliance).

PAM50 intrinsic breast cancer subtypes are prognostic independent of standard clinicopathologic factors. CALGB 9741 demonstrated improved recurrence-free (RFS) and overall survival (OS) with 2-weekly dose-dense (DD) versus 3-weekly therapy. A significant interaction between intrinsic subtypes and DD-therapy benefit was hypothesized.

Molecular Heterogeneity and Response to Neoadjuvant Human Epidermal Growth Factor Receptor 2 Targeting in CALGB 40601, a Randomized Phase III Trial of Paclitaxel Plus Trastuzumab With or Without Lapatinib.

Purpose: Dual human epidermal growth factor receptor 2 (HER2) targeting can increase pathologic complete response rates (pCRs) to neoadjuvant therapy and improve progression-free survival in metastatic disease. CALGB 40601 examined the impact of dual HER2 blockade consisting of trastuzumab and lapatinib added to paclitaxel, considering tumor and microenvironment molecular features.

Patients And Methods: Patients with stage II to III HER2-positive breast cancer underwent tumor biopsy followed by random assignment to paclitaxel plus trastuzumab alone (TH) or with the addition of lapatinib (THL) for 16 weeks before surgery.

Randomized Trial of Lenalidomide Alone Versus Lenalidomide Plus Rituximab in Patients With Recurrent Follicular Lymphoma: CALGB 50401 (Alliance).

Purpose: Lenalidomide and rituximab (LR) are active agents in follicular lymphoma (FL). Combination regimens have not been previously assessed in randomized studies.

Patients And Methods: The Cancer and Leukemia Group B (Alliance) 50401 trial is a randomized phase II trial studying rituximab (375 mg/m(2) weekly for 4 weeks), lenalidomide (15 mg per day on days 1 to 21, followed by 7 days of rest, in cycle 1 and then 20 mg per day on days 1 to 21, followed by 7 days of rest, in cycles 2 to 12), or LR.

Comorbidity, chemotherapy toxicity, and outcomes among older women receiving adjuvant chemotherapy for breast cancer on a clinical trial: CALGB 49907 and CALGB 361004 (alliance).

Purpose: We evaluated associations among comorbidity, toxicity, time to relapse (TTR), and overall survival (OS) in older women with early-stage breast cancer receiving adjuvant chemotherapy.

Methods: Cancer and Leukemia Group B 49907 (Alliance) randomly assigned women ≥ 65 years old with stages I-III breast cancer to standard adjuvant chemotherapy or capecitabine. We reviewed data from 329 women who participated in the quality of life companion study CALGB 70103 and completed the Physical Health Subscale of the Older American Resources and Services Questionnaire.

Therapy with bortezomib plus lenalidomide for relapsed/refractory mantle cell lymphoma: final results of a phase II trial (CALGB 50501).

Cancer and Leukemia Group B designed a phase II trial of lenalidomide + bortezomib for relapsed/refractory mantle cell lymphoma (MCL). Induction therapy was lenalidomide (days 1-14) plus bortezomib (days 1/4/8/11), every 21 days for eight cycles. Complete/partial responders (CR, PR) received maintenance lenalidomide (days 1-14) and bortezomib (days 1/8), every 21 days.

CALGB 150905 (Alliance): rituximab broadens the antilymphoma response by activating unlicensed NK cells.

Natural killer (NK) cells contribute to clinical responses in patients treated with rituximab, but the rules determining NK-cell responsiveness to mAb therapies are poorly defined. A deeper understanding of the mechanisms responsible for antibody-dependent cellular cytotoxicity (ADCC) could yield useful biomarkers for predicting clinical responses in patients. Unlicensed NK cells, defined as NK cells lacking expression of an inhibitory KIR for self-HLA class I ligands, are hyporesponsive in steady state, but are potent effectors in inflammatory conditions.