Salvage Focal Cryotherapy Offers Similar Short-term Oncologic Control and Improved Urinary Function Compared With Salvage Whole Gland Cryotherapy for Radiation-resistant or Recurrent Prostate Cancer

BackgroundWe compared the short-term oncologic and functional outcomes of salvage focal cryotherapy (SFC) with those of salvage total cryotherapy (STC) for radiotherapy (RT)-persistent/recurrent prostate cancer.Materials and MethodsWe queried the Cryo On-Line Database registry for men who had undergone SFC and STC of the prostate for RT-persistent or recurrent disease. Propensity score weighting was used to match age at treatment, presalvage therapy prostate-specific antigen level, Gleason sum, and presalvage cryotherapy androgen deprivation therapy status. The primary outcome was progression-free survival.ResultsA total of 385 men with biopsy-proven persistent or recurrent prostate cancer after primary RT were included in the present study. The median follow-up, age, prostate-specific antigen, and Gleason sum before salvage cryotherapy was 24.4 months (first and third quartile, 9.8 and 60.3), 70 years (first and third quartile, 66 and 74 years), 4 ng/dL (first and third quartile, 2.7 and 5.6 ng/dL), and 7 (first and third quartile, 6 and 8), respectively. After propensity score weighting, the difference in progression-free survival was not statistically significant between the patients who had undergone STC and those who had undergone SFC (79.8% vs. 76.98%; P = .11 on weighted log-rank test). SFC was associated with a lower probability of post-treatment transient urinary retention (5.6% vs. 22.4%; P < .001). No significant differences were found in the incidence of rectal fistula (1.4% vs. 3.8; P = .30), new-onset urinary incontinence within 12 months (9.3% vs. 15.1%; P = .19), or new-onset erectile dysfunction within 12 months (52.6% vs. 59.6%; P = .47) between the SFC and STC groups, respectively.ConclusionsSTC resulted in similar 2-year oncologic outcomes compared with SFC in the RT-persistent/recurrent disease population. However, the patients who had undergone SFC had a lower urinary retention rate compared with those who had undergone STC.     

Therapeutic effect of mesenchymal stem cell on Hashimoto’s thyroiditis in a rat model by modulating Th17/Treg cell balance

Abstract

The autoimmune condition Hashimoto’s thyroiditis (HT) is a disease wherein lymphocytes mediate the autoimmune damage and destruction of the thyroid gland. There are currently no effective means of treating HT, with the primary strategies of thyroid hormone therapy, surgery, or immunomodulatory therapy being associated with serious risks and side effects. There is thus a clear and urgent need to identify novel treatments for HT. In this study, we utilize female SD rats induced HT to evaluated the ability of transplanted MSCs to regulate Th17/Treg interactions in a rat Hashimoto’s thyroiditis (HT) model system. The results showed that Rats in the HT model group exhibited increased thyroid autoantibody levels consistent with successful model development, whereas these levels were lower in rats treated with MSCs. There were also fewer thyroid lesions and less lymphoid infiltration of the thyroid in MSC-treated rats relative to HT model rats, as well as fewer Th17 cells and more Treg cells – an observation consistent with the cytokine analyses. All of these showed that MSCs can regulate Th17/Treg interactions in a rat Hashimoto’s thyroiditis (HT) model system. It suggested that transplanted MSCs could be a potential immunotherapy strategy for the treatment of Hashimoto’s thyroiditis.     

Results From a Large,Multicenter, Retrospective Analysis On Radium223 Use in Metastatic Castration-resistant Prostate Cancer (mCRPC) in the Triveneto Italian Region

Background

Radium 223 was introduced for metastatic castration-resistant prostate cancer based on the results of a randomized controlled trial showing risk reduction for death and skeletal events. Our aim was to evaluate the outcome of patients receiving radium 223 in a real-world setting.

Phase 1 Study of Erlotinib and Metformin in Metastatic Triple-Negative Breast Cancer

BackgroundEpidermal growth factor receptor (EGFR) is frequently overexpressed in metastatic triple-negative breast cancer (mTNBC). One strategy for overcoming resistance to EGFR inhibition is concomitant inhibition of downstream signaling. The antidiabetic drug metformin inhibits both MAPK and PI3K/mTOR pathway signaling. We evaluated the combination of erlotinib and metformin in a phase 1 study of patients with mTNBC.Patients and MethodsPatients with mTNBC who had received at least one prior line of therapy for metastatic disease were eligible. Erlotinib dose was fixed at 150 mg daily. Metformin dose escalation was planned according to a 3 + 3 design. Dose-limiting toxicities (DLT) were assessed during the first 5 weeks of therapy. The primary objective was to determine the maximum tolerated dose of metformin with fixed-dose erlotinib. Secondary endpoints were response rate, stable disease rate, and progression-free survival.ResultsEight patients were enrolled. The median number of prior therapies for metastatic disease was 2.5 (range, 1-6). No DLT events were reported during the DLT assessment period. Most adverse events were grade 1/2. Grade 3 diarrhea despite maximum supportive care required dose reduction of metformin in one patient. Grade 3 rash led to study withdrawal in one patient. No grade 4 adverse events were reported. The best observed response was stable disease in 2 patients (25%). Median progression-free survival was 60 days (range, 36-61 days).ConclusionErlotinib and metformin were well tolerated in a population of pretreated mTNBC patients but did not demonstrate efficacy in this population.     

Response to chemoradiotherapy and lymph node involvement in locally advanced rectal cancer

AIM: To establish the association between lymph node involvement and the response to neoadjuvant therapy in locally advanced rectal cancer.METHODS: Data of 130 patients with mid and low locally advanced rectal adenocarcinoma treated with neoadjuvant chemoradiation followed by radical surgery over a 5-year period were reviewed. Tumor staging was done by endorectal ultrasound and/or magnetic resonance imaging. Tumor response to neoadjuvant therapy was determined by T-downstaging and tumor regression grading (TRG). Pathologic complete response (pCR) is defined as the absence of tumor cells in the surgical specimen (ypT0N0). The varying degrees TRG were classified according to Mandard’s scoring system. The evaluation of the response is based on the comparison between previous clinico-radiological staging and the results of pathological evaluation. χ² and Spearman’s correlation tests were used for the comparison of variables.RESULTS: Pathologic complete response (pCR, ypT0N0, TRG1) was observed in 19 cases (14.6%), and other 18 (13.8%) had only very few residual malignant cells in the rectal wall (TRG2). T-downstaging was found in 63 (48.5%). Mean lymph node retrieval was 9.4 (range 0-38). In 37 cases (28.5%) more than 12 nodes were identified in the surgical specimen. Preoperative lymph node involvement was seen in 77 patients (59.2%), 71 N1 and 6 N2. Postoperative lymph node involvement was observed in 41 patients (31.5%), 29 N1 and 12 N2, while the remaining 89 were N0 (68.5%). In relation to ypT stage, we found nodal involvement of 9.4% in ypT0-1, 22.2% in ypT2 and 43.7% in ypT3-4. Of the 37 patients considered “responders” to neoadjuvant therapy (TRG1 and 2), there were only 4 N+ (10.8%) and the remainder N0 (89.2%). In the “non responders” group (TRG 3, 4 and 5), 37 cases were N+ (39.8%) and 56 (60.2%) were N0 (P < 0.001).CONCLUSION: Response to neoadjuvant chemoradiation in rectal cancer is associated with lymph node involvement.