Predictors of complete pathological response after neoadjuvant systemic therapy for breast cancer

Background

The aim of the current study was to identify predictors of pathologic complete response (pCR) following neoadjuvant therapy.

Methods

From 2000 to 2007, 518 breast cancer patients received neoadjuvant therapy. Data were compared using χ² and Fisher's exact tests and multivariate analysis of variance, as appropriate.

Results

Of 518 breast cancer patients receiving neoadjuvant therapy, 81 (16%) had pCR (77 of 456 [17%] with chemotherapy, 4 of 62 [6%] with endocrine therapy; P < .05). Four factors were associated with pCR: higher tumor grade (P = .015), lack of estrogen receptor (ER) and progesterone receptor (PR) expression (P < .0001), HER2/neu amplification (P = .025), and negative lymph node status (P < .0001). On multivariate analysis, ER and PR negativity, HER2/neu amplification, and negative lymph node status were found to significantly correlate with pCR.

Conclusions

Patients with ER-negative and PR-negative and HER2/neu-amplified breast cancer phenotypes are more likely to experience pCR to neoadjuvant therapy. Although pCR is more frequently observed following neoadjuvant chemotherapy, it is rare following neoadjuvant endocrine therapy.     

Considerations on in vitro and in vivo magnetic nanoparticles hemocompatibility testing

The aim of this paper is to summarize few aspects and underline some difficulties that hemocompatibility testing come up. The purpose of hemocompatibility testing is to look for possible undesirable changes in the blood caused directly by a medical device, by chemicals leaching from a device or biomaterials. Undesirable effects of device materials on the blood may include alterations in coagulation parameters, thrombus formation, hemolysis, and immunological changes. For each different event the literature is rich in showing tests, not different in principle, but in testing conditions. ISO 10993-4 describes hemocompatibility tests in five different categories (thrombosis, coagulation, platelets, hematology, and immunology). Here we put together the tests that ISO 10993 and/or American Society for Testing and Materials (ASTM) suggest to evaluate hemocompatibility and we emphases on their utility for magnetic nanoparticules testing. The individual tests are not discussed in detail; they may be performed either in vivo or, preferably, in vitro. For each test we made few considerations with criticism. There is still some uncertainty with respect to what is actually required by the regulatory authorities for the hemocompatibility test, and there is still no harmony between ASTM and ISO 10993 regulations regarding some aspects to be standardised.     

Desmoplastic small round cell tumor in children: a new therapeutic approach

Purpose

Desmoplastic small round cell tumor (DSRCT) is a rare, highly aggressive malignancy with distinctive histologic and immunohistochemical features occurring in a young population with a male predominance. The tumor appears to arise as masses in the abdominal cavity without a clear visceral origin. Five patients with DSRCT were treated as usual with combined chemoradiation and surgery. In addition, in our center, patients underwent autologous bone marrow transplant (BMT), which is a novel approach to this disease.

Methods

Charts of 5 patients (4 males, mean age of 11 years) treated between 2000 and 2007 were reviewed. The diagnosis of DSRCT was made on the basis of clinical examination, computed tomographic scan, and explorative laparotomy with biopsy, and biochemical markers were negative. All patients were treated with aggressive chemoradiation and surgery. Three patients also had autologous BMT.

Results

Three patients (BMT recipients) responded to treatment. The responding patients had surgery with the intent of removing all disease. Two patients died of their cancer, neither of whom underwent BMT.

Conclusion

The patients DSRCT are sensitive to an aggressive combination of chemotherapy, surgical debulking, and radiation therapy, followed by autologous BMT. It appears that this new multifaceted treatment offers good palliation, which may prolong survival and a possible cure.     

DAA‐based antiviral treatment of patients with chronic hepatitis C in the pre‐ and postkidney transplantation setting

DAA‐based regimens for chronic hepatitis C infection encourage treatment of “difficult‐to‐treat” cohorts. This study investigated efficacy and safety of DAA‐based regimens in HCV patients on dialysis or postkidney or liver/kidney transplantation. Twenty‐five patients treated with DAA combinations were evaluated: 10 were on dialysis (eight: hemodialysis, two: peritoneal dialysis), eight were kidney transplant recipients, and seven were liver/kidney transplant recipients. Except for one patient treated with daclatasvir ([DCV]/60 mg/QD)/simeprevir ([SMV]/150 mg/QD), the others received sofosbuvir‐based regimens ([SOF];400 mg/QD) combined with SMV:eight, DCV:13 or either ledipasvir ([LDV]90 mg/QD), ribavirin ([RBV];weight based) or pegylated interferon/RBV. HCV‐RNA was determined by Abbott RealTime (LLOQ]:12 IU/ml) or Roche AmpliPrep/COBAS TaqMan assay (LLOQ:15 IU/ml); treatment response evaluated every 4 weeks, at the end of treatment, and 4 and 12 weeks thereafter. Twenty‐four (96%) patients achieved SVR 12/24 (ITT‐analysis). Mean treatment duration was 15.1 ± 5.1 weeks (±SD), and two patients terminated prematurely – both reached SVR12. Six patients were hospitalized due to complications of underlying disease. One patient achieved SVR24 but was re‐infected (week 27). Kidney function remained stable; serum creatinine increased in only one patient – SOF was reduced to 400 mg/48 h. Treatment with DAA combinations in renally impaired HCV patients is highly effective and well tolerated. These findings call for further controlled trials and data from real‐life cohorts.     

A possible protocol for postoperative management in laparoscopic cholecystectomy

The goal of the "Prospect" programme (sponsored by Pfizer) is to create possible evidence-based protocols related to the management of postoperative pain after certain type of surgical intervention (e.g. hernia repairs, hysterectomies, etc.). This article is introducing the protocol for laparoscopic cholecystectomy for both day-case and longer hospital admission cases. The protocol is designed for preoperative, intra and postoperative period, choosing only those measures which were effective for postoperative pain, published in the literature. We are also presenting an analyze of our 13,000 laparoscopic cholecystectomies, from "Prospect" protocol point of view, and what we should do to improve the management of postoperative pain.     

Long-stay patients in pediatric intensive care units: Five-years, 2-points,cross-sectional study

Objectives:To explore the changing patterns of long-stay patients (LSP) to improve the utilization of pediatric intensive care units (PICUs) resources.Methods:This is a 2-points cross-sectional study (5 years apart; 2014-2019) conducted among PICUs and SCICUs in Riyadh, Saudi Arabia. Children who have stayed in PICU for more than 21 days were included.Results:Out of the 11 units approached, 10 (90%) agreed to participate. The prevalence of LSP in all these hospitals decreased from 32% (48/150) in 2014 to 23.4% (35/149) in 2019. The length of stay ranged from 22 days to 13.5 years. The majority of LSP had a neuromuscular or cardiac disease and were admitted with respiratory compromise. Ventilator-associated pneumonia was the most prevalent complication (37.5%). The most commonly used resources were mechanical ventilation (93.8%), antibiotics (60.4%), and blood-products transfusions (35.4%). The most common reason for the extended stay was medical reasons (51.1%), followed by a lack of family resources (26.5%) or lack of referral to long-term care facilities (22.4%).Conclusion:A long-stay is associated with significant critical care bed occupancy, complications, and utilization of resources that could be otherwise utilized as surge capacity for critical care services. Decreasing occupancy in this multicenter study deserves further engagement of the healthcare leaders and families to maximize the utilization of resources.     

Fluorouracil, mitomycin, and radiotherapy vs fluorouracil, cisplatin, and radiotherapy for carcinoma of the anal canal: a randomized controlled trial

Jaffer A. Ajani, MD; Kathryn A. Winter, MS; Leonard L. Gunderson, MD; John Pedersen, MD; Al B. Benson III, MD; Charles R. Thomas Jr, MD; Robert J. Mayer, MD; Michael G. Haddock, MD; Tyvin A. Rich, MD; Christopher Willett, MD

JAMA. 2008;299(16):1914-1921.

Context  Chemoradiation as definitive therapy is the preferred primary therapy for patients with anal canal carcinoma; however, the 5-year disease-free survival rate from concurrent fluorouracil/mitomycin and radiation is only approximately 65%.

Objective  To compare the efficacy of cisplatin-based (experimental) therapy vs mitomycin-based (standard) therapy in treatment of anal canal carcinoma.

Design, Setting, and Participants  US Gastrointestinal Intergroup trial RTOG 98-11, a multicenter, phase 3, randomized controlled trial comparing treatment with fluorouracil plus mitomycin and radiotherapy vs treatment with fluorouracil plus cisplatin and radiotherapy in 682 patients with anal canal carcinoma enrolled between October 31, 1998, and June 27, 2005. Stratifications included sex, clinical nodal status, and tumor diameter.

Intervention  Participants were randomly assigned to 1 of 2 intervention groups: (1) the mitomycin-based group (n = 341), who received fluorouracil (1000 mg/m² on days 1-4 and 29-32) plus mitomycin (10 mg/m² on days 1 and 29) and radiotherapy (45-59 Gy) or (2) the cisplatin-based group (n = 341), who received fluorouracil (1000 mg/m² on days 1-4, 29-32, 57-60, and 85-88) plus cisplatin (75 mg/m² on days 1, 29, 57, and 85) and radiotherapy (45-59 Gy; start day = day 57).

Main Outcome Measures  The primary end point was 5-year disease-free survival; secondary end points were overall survival and time to relapse.

Results  A total of 644 patients were assessable. The median follow-up for all patients was 2.51 years. Median age was 55 years, 69% were women, 27% had a tumor diameter greater than 5 cm, and 26% had clinically positive nodes. The 5-year disease-free survival rate was 60% (95% confidence interval [CI], 53%-67%) in the mitomycin-based group and 54% (95% CI, 46%-60%) in the cisplatin-based group (P = .17). The 5-year overall survival rate was 75% (95% CI, 67%-81%) in the mitomycin-based group and 70% (95% CI, 63%-76%) in the cisplatin-based group (P = .10). The 5-year local-regional recurrence and distant metastasis rates were 25% (95% CI, 20%-30%) and 15% (95% CI, 10%-20%), respectively, for mitomycin-based treatment and 33% (95% CI, 27%-40%) and 19% (95% CI, 14%-24%), respectively, for cisplatin-based treatment. The cumulative rate of colostomy was significantly better for mitomycin-based than cisplatin-based treatment (10% vs 19%; P = .02). Severe hematologic toxicity was worse with mitomycin-based treatment (P < .001).

Conclusions  In this population of patients with anal canal carcinoma, cisplatin-based therapy failed to improve disease-free-survival compared with mitomycin-based therapy, but cisplatin-based therapy resulted in a significantly worse colostomy rate. These findings do not support the use of cisplatin in place of mitomycin in combination with fluorouracil and radiotherapy in the treatment of anal canal carcinoma.

Trial Registration  clinicaltrials.gov Identifier: NCT00003596