Safety and efficacy analysis of neoadjuvant pertuzumab, trastuzumab and standard chemotherapy for HER2-positive early breast cancer: real-world data from NeoPowER study.

BACKGROUND: The addition of pertuzumab (P) to trastuzumab (H) and standard chemotherapy (CT) as neoadjuvant treatment (NaT) for patients with HER2 + breast cancer (BC), has shown to increase the pathological complete response (pCR) rate, without main safety concerns. The aim of NeoPowER trial is to evaluate safety and efficacy of P + H + CT in a real-world population. METHODS: We retrospectively reviewed the medical records of stage II-III, HER2 + BC patients treated with NaT: who received P + H + CT (neopower group) in 5 Emilia Romagna institutions were compared with an historical group who received H + CT (control group). The primary endpoint was the safety, secondary endpoints were pCR rate, DRFS and OS and their correlation to NaT and other potential variables. RESULTS: 260 patients were included, 48% received P + H + CT, of whom 44% was given anthraciclynes as part of CT, compared to 83% in the control group. The toxicity profile was similar, excluding diarrhea more frequent in the neopower group (20% vs. 9%). Three patients experienced significant reductions in left ventricular ejection fraction (LVEF), all receiving anthracyclines. The pCR rate was 46% (P + H + CT) and 40% (H + CT) (p = 0.39). The addition of P had statistically correlation with pCR only in the patients receiving anthra-free regimens (OR = 3.05,p = 0.047). Preoperative use of anthracyclines (OR = 1.81,p = 0.03) and duration of NaT (OR = 1.18,p = 0.02) were statistically related to pCR. 12/21 distant-relapse events and 14/17 deaths occurred in the control group. Patients who achieve pCR had a significant increase in DRFS (HR = 0.23,p = 0.009). CONCLUSIONS: Adding neoadjuvant P to H and CT is safe. With the exception of diarrhea, rate of adverse events of grade > 2 did not differ between the two groups. P did not increase the cardiotoxicity when added to H + CT, nevertheless in our population all cardiac events occurred in patients who received anthracycline-containing regimens. Not statistically significant, higher pCR rate is achievable in patients receiving neoadjuvant P + H + CT. The study did not show a statistically significant correlation between the addition of P and long-term outcomes.

Supervised learning with word embeddings derived from PubMed captures latent knowledge about protein kinases and cancer.

Inhibiting protein kinases (PKs) that cause cancers has been an important topic in cancer therapy for years. So far, almost 8% of >530 PKs have been targeted by FDA-approved medications, and around 150 protein kinase inhibitors (PKIs) have been tested in clinical trials. We present an approach based on natural language processing and machine learning to investigate the relations between PKs and cancers, predicting PKs whose inhibition would be efficacious to treat a certain cancer. Our approach represents PKs and cancers as semantically meaningful 100-dimensional vectors based on word and concept neighborhoods in PubMed abstracts. We use information about phase I-IV trials in ClinicalTrials.gov to construct a training set for random forest classification. Our results with historical data show that associations between PKs and specific cancers can be predicted years in advance with good accuracy. Our tool can be used to predict the relevance of inhibiting PKs for specific cancers and to support the design of well-focused clinical trials to discover novel PKIs for cancer therapy.

Minimally Invasive Video-Assisted Thyroidectomy: Analysis of Complications From a Systematic Review.

BACKGROUND: Nowadays, minimally invasive video-assisted thyroidectomy (MIVAT) is considered a safe and effective option. However, its complication rate has not been specifically discussed yet. The aim of this systematic review was enrolling a large number of studies to estimate early and late complications (transient and definitive, uni- and bilateral laryngeal nerve palsy; transient and definitive hypocalcemia; cervical hematoma; hypertrophic or keloid scar) of MIVAT compared with conventional technique. METHODS: The review was performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria in PubMed and Embase. Search terms were "minimally invasive," "video-assisted," and "thyroidectomy." We enrolled randomized clinical trials, nonrandomized trials, and noncontrolled trials. RESULTS: Thirty-two articles were considered suitable. Complication rate of MIVAT was quite similar to conventional technique: only one randomized trial found a significant difference concerning overall skin complication, and a single trial highlighted hypocalcemia significantly increased in MIVAT, concerning serologic value only. No difference concerning symptomatic nor definitive hypocalcemia was found. CONCLUSIONS: We can confirm that MIVAT is a safe technique. It should be adopted in mean-high-volume surgery centers for thyroidectomy, if a strict compliance with indication was applied.

Laparoscopy is an available alternative to open surgery in the treatment of perforated peptic ulcers: a retrospective multicenter study.

BACKGROUND: Perforated peptic ulcers (PPU) remain one of the most frequent causes of death. Their incidence are largely unchanged accounting for 2-4% of peptic ulcers and remain the second most frequent abdominal cause of perforation and of indication for gastric emergency surgery. The minimally invasive approach has been proposed to treat PPU however some concerns on the offered advantages remain. METHODS: Data on 184 consecutive patients undergoing surgery for PPU were collected. Likewise, perioperative data including shock at admission and interval between admission and surgery to evaluate the Boey's score. It was recorded the laparoscopic or open treatments, the type of surgical procedure, the length of the operation, the intensive care needed, and the length of hospital stay. Post-operative morbidity and mortality relation with patient's age, surgical technique and Boey's score were evaluated. RESULTS: The relationship between laparoscopic or open treatment and the Boey's score was statistically significant (p = 0.000) being the open technique used for the low-mid group in 41.1% and high score group in 100% and laparoscopy in 58.6% and 0%, respectively. Postoperative complications occurred in 9.7% of patients which were related to the patients' Boey's score, 4.7% in the low-mid score group and 21.4% in the high risk score group (p = 0.000). In contrast morbidity was not related to the chosen technique being 12.8% in open technique and 5.3% in laparoscopic one (p = 0.092, p > 0.05). 30-day post-operative mortality was 3.8% and occurred in the 0.8% of low-mid Boey's score group and in the 10.7% of the high Boey's score group (p = 0.001). In respect to the surgical technique it occurred in 6.4% of open procedures and in any case in the Lap one (p = 0.043). Finally, there was a statistically significant difference in morbidity and mortality between patients < 70 and > 70 years old (p = 0.000; p = 0.002). CONCLUSIONS: Laparoscopy tends to be an alternative method to open surgery in the treatment of perforated peptic ulcer. Morbidity and mortality were essentially related to Boey's score. In our series laparoscopy was not used in high risk Boey's score patients and it will be interesting to evaluate its usefulness in high risk patients in large randomized controlled trials.