Percutaneous comprehensive cryoablation for metastatic esophageal cancer after failure of radical surgery

Esophageal cancer is common in China. There is a lack of treatment strategies for metastatic esophageal cancer (MEC) after radical surgery on the primary tumor. Cryoablation is an attractive option because tumor necrosis can be safely induced in a minimally invasive manner. This study assessed its therapeutic effect in MEC after failure of radical surgery. One hundred and forty patients met the inclusion criteria from May, 2003 to March, 2011. Comprehensive cryotherapy of multiple metastases was performed on 105 patients; 35 received chemotherapy. No severe complications occurred during or after cryoablation. Overall survival (OS) was assessed according to therapeutic protocol, pathologic type, treatment timing and number of procedures. The OS of patients who received comprehensive cryoablation (44 ± 20 months) was significantly longer than that of those who underwent chemotherapy (23 ± 24 months; P = 0.0006). In the cryotherapy group, the OS for squamous cell carcinoma (45 ± 19 months) was longer than that for adenocarcinoma (33 ± 18 months; P = 0.0435); the OS for timely cryoablation (46 ± 19 months) was longer than that for delayed cryoablation (33 ± 20 months; P = 0.0193); the OS for multiple cryoablation (50 ± 17 months) was longer than that for single cryoablation (37 ± 20 months; P = 0.0172); and the OS for cryo-immunotherapy (56 ± 17 months) was longer than that for cryoablation alone (39 ± 19 months; P = 0.0011). Thus, comprehensive cryotherapy may have advantages over chemotherapy in the treatment of MEC and, in patients with squamous cell carcinoma, supplementary immunotherapy and timely and multiple cryoablation may be associated with a better prognosis.     

Therapeutic outcomes of combining cryotherapy,chemotherapy and DC-CIK immunotherapy in the treatment of metastatic non-small cell lung cancer

Currently there are no effective therapies for the treatment of metastatic non-small cell lung cancer (NSCLC). Here, we conducted a retrospective study of 161 patients to evaluate the therapeutic effects of combining cryosurgery, chemotherapy and dendritic cell-activated cytokine-induced killer cells (DC-CIK) immunotherapy. The overall survival (OS) after diagnosis of metastatic NSCLC to patient death was assessed during a 5-years follow-up period. OS of patients who received comprehensive cryotherapy was (median OS, 20 months; n = 86) significantly longer than that of patients who did not received cryotherapy (median OS, 10 months; n = 75; P < 0.0001). Five treatment combinations were selected: chemotherapy (n = 44); chemo-immunotherapy (n = 31); cryo-chemotherapy (n = 32); cryo-immunotherapy (n = 21); and cryo-chemo-immunotherapy (n = 33). A combination of cryotherapy with either chemotherapy or immunotherapy lead to significantly longer OS (18 months and 17 months, respectively) compared to chemotherapy and chemo-immunotherapy (8.5 months and 12 months, respectively; P < 0.001); however, the median OS of patients who underwent cryo-chemo-immunotherapy was significantly longer (27 months) compared to the other treatment programs (P < 0.001). In conclusion, a combination of cryotherapy, chemotherapy and DC-CIK immunotherapy proved the best treatment option for metastatic NSCLC in this group of patients.     

Percutaneous cryoablation for stage IV lung cancer: A retrospective analysis

The aim of this study was to investigate the therapeutic effect of cryoablation treatment and palliative treatment in stage IV lung cancer. Fifty-four patients were enrolled into the study. Thirty-one patients received cryoablation treatment (including intra- and extrapulmonary tumors), and 23 patients had palliative treatment (no cryoablation). Both the safety of the procedure and overall survival (OS) for stage IV lung cancer were assessed during a 6.5 year follow-up period. The OS of patients in both groups and the effects of treatment timing and frequency were compared. The OS in the cryoablation group was significantly longer than in the palliative group (median OS: 14 months vs. 7 months, P = 0.0009). The OS of those who received delayed cryoablation treatment was longer than that observed for those who received timely treatment (median OS: 18.5 months vs. 10 months, P = 0.0485), but this was not observed in those who received palliative treatment (median OS: 7 months vs. 7.5 months, P = 0.9814). Multiple treatments played an important role in improving the OS of patients who received cryoablation treatment (median OS: 18 months vs. 14 months, P = 0.0376). There was a significant difference between cryoablation and palliative treatment, in terms of OS. In addition, multiple cryoablation treatments may have an advantage over single treatments.     

Comprehensive treatment of malignant mesothelioma patients after the failure of systemic chemotherapy

Malignant mesothelioma (MM) is an aggressive neoplasm usually arising from the mesothelial surfaces of the pleural or peritoneal cavity. Currently, no standard therapy is available. The most commonly used therapy is cytoreductive surgery combined with systematic chemotherapy, but the median overall survival (OS) is less than 12 months; moreover, treatments are lacking for patients in whom chemotherapy has failed and/or who cannot withstand surgery. We investigated multiple minimally invasive therapies (cryosurgery, photodynamic therapy and intracavity chemotherapy) for the treatment of MM patients in whom systemic chemotherapy had failed. Twenty-seven patients were divided into comprehensive (combination of the three therapies) and palliative (intracavity chemotherapy only) treatment groups. The OS of patients who received comprehensive treatment was significantly longer than that of those who received palliative treatment (median OS: 64 vs. 9 months, P < 0.001). This interesting result was not associated with treatment timing, but was closely associated with repeated treatments.     

CT-guided percutaneous cryoablation combined with systemic chemotherapy for liver metastases from esophageal carcinoma: Initial experience

ObjectiveTo explore the feasibility, safety and effectiveness of percutaneous cryoablation combined with systemic chemotherapy in the treatment of liver metastases from esophageal carcinoma (ECLM).Materials and methodsWe retrospectively collected data of 16 patients who received CT-guided percutaneous cryoablation concurrent systemic chemotherapy for liver metastases after primary esophageal carcinoma resection. Functional Assessment of Cancer Therapy-General (FACT-G) was used for the assessment of quality of life (QOL), and overall survival (OS), progression-free survival (PFS) and complications were also evaluated.ResultsThe technical success rate was 96%, and no major complications related to cryoablation procedure were detected. Median OS and PFS after cryoablation were 14.5 months (range, 4–51 months) and 7.5 months (range, 1–31 months), respectively. The 1-year, 2-year, and 3-year survival rates were 56.3%, 31.3%, and 18.8%, respectively. The PFS rate at 6-month, 1-year, and 2-year after procedure were 68.8%, 31.3% and 18.8%, respectively. Furthermore, the QOL of patients was improved after cryoablation therapy compared with preoperative scores (P < 0.05).ConclusionsPercutaneous cryoablation combined with systemic chemotherapy is a safe, feasible and effective method to treat liver metastases from esophageal carcinoma. And to a certain extent, this approach is very efficacious in improving the QOL of patients with ECLM.     

Percutaneous cryotherapy for metastatic bladder cancer: Experience with 23 patients

Bladder cancer is the most common malignancy of the urinary tract and in many patients is metastatic at diagnosis. Chemotherapy is the standard treatment for these patients but has serious side effects and in many patients is not tolerated. To avoid the side effects of systemic chemotherapy, patients with late stage bladder cancer have sought cryotherapy in our hospital. We reviewed data for the past 4 years to evaluate the safety and efficiency of percutaneous cryotherapy in 23 patients. Within 3 days after cryosurgery, all complications of bladder cancer (e.g. hematuria, urinary irritation, hypogastralgia, lumbago) had decreased to some degree. No new complications (e.g. bladder perforation) occurred and all complications had disappeared completely after 2 weeks. The progression-free survival (PFS) of these patients was 14 ± 8 months. There was no effect on PFS of tumor location or histopathology; however, differentiation status and tumor size influenced the therapeutic effect of percutaneous cryoablation. In conclusion, percutaneous cryotherapy may be a safe and efficacious therapeutic option in the treatment of metastatic bladder cancer.     

Prognostic Role of Adjuvant Chemotherapy in Node-Negative (N0), Triple-Negative (TN), Medullary Breast Cancer (MBC) in the Korean Population

Background

Despite the favorable prognosis for medullary breast cancer (MBC), the guidelines for the use of adjuvant chemotherapy for MBC have not been clearly established. This study investigated the prognostic role of adjuvant chemotherapy in Korean patients with node-negative (N0), triple-negative (TN) MBC patients.

Methods

We included data from 252 patients with N0 TN MBC, obtained from the Korean Breast Cancer Registry database. Patients were categorized as those who did not undergo adjuvant chemotherapy (group I) or those who did (group II). Clinicopathological characteristics, breast cancer-specific survival (BCSS), and overall survival (OS) were compared between the groups. In addition, a subgroup analysis for survival based on tumor size was conducted.

Results

A total of 252 N0 TN MBC patients with tumor sizes >1 cm who were diagnosed between April 1997 and March 2011 were enrolled. The median age was 44.95 years (range, 25–72 years), and the median follow-up period was 93.94 months (range, 23–195 months). Overall, the BCSS and OS in group II (97.3% and 97.3%, respectively) were significantly better compared with those in group I (89.2% and 86.2%, respectively). In the subgroup analysis, in patients with tumors >2 cm in size, those in group II had significant better BCSS and OS (97.5% and 97.5%, respectively) compared with those in group I (78.3% and 73.9%, respectively). In contrast in those with tumors 1–2 cm in size, there were no significant differences in BCSS and OS between the groups (both 97.1% for group I, and 95.2% and 92.9%, respectively for group II). Multivariate analysis revealed that adjuvant chemotherapy significantly improved BCSS (P = 0.009) and OS (P = 0.007), but only for patients with larger tumors (>2 cm).

Conclusions

In patients with N0 TN MBC, adjuvant chemotherapy had a significant clinical survival benefit, but only in those with tumors >2 cm.     

Combination percutaneous cryotherapy and iodine-125 seed implantation for unresectable malignant thymoma: Experience in 19 patients

Thymomas are the most common tumors of the mediastinum. These tumors often compress vital mediastinal organs and severely impact the quality of life of thymoma patients. To avoid the side effects of chemoradiotherapy, some patients with unresectable malignant thymomas have opted to undergo cryotherapy in our hospital. We reviewed the cryosurgery, nursing and follow-up records of our hospital for the past 8 years, and evaluated the safety and efficiency of cryotherapy in 19 patients with unresectable malignant thymomas. No severe complications involving the vital organs surrounding the tumor occurred during or after cryosurgery. The most common side effect was pleural effusion, which occurred in 11 patients and healed after drainage within 1 week. Cough, mediastinal and pericardial effusions, pneumothorax, mild fever and chest tightness also occurred and resolved 1 week after symptomatic treatment. Since our patients had high KPS scores and mild myasthenia gravis symptoms before the treatment, myasthenia gravis did not occur after the treatment. The progression-free survival of the patients was 14–29 months (median, 18 months), and did not differ between patients with large tumors and those with small tumors (P = 0.6753). In conclusion, cryotherapy is a safe and efficient method for the treatment of unresectable malignant thymoma.     

Role of EGFR SNPs in survival of advanced lung adenocarcinoma patients treated with Gefitinib

Aim

As a novel molecularly targeting agent for non-small-cell lung cancer (NSCLC), Gefitinib can block its tyrosine kinase activity of the epidermal growth factor receptor (EGFR). Genetic variations in EGFR may affect its protein function or expression and lead to diverse outcomes in NSCLC patients after Gefitinib therapy. Therefore, this prospective study examined whether EGFR single nucleotide polymorphisms (SNPs) are associated with different survival time in advanced lung adenocarcinoma patients treated with Gefitinib.

Methods

One hundred and twenty-eight patients with stage IIIB or IV lung adenocarcinoma receiving Gefitinib target therapy between 2008 and 2010 were recruited in this study. Six EGFR haplotype-tagging SNPs were genotyped by the Sequenom MassArray system. Survival by different genotypes was compared using Kaplan–Meier methods. Cox proportional hazards models were applied to estimate the effect of prognostic factors on overall survival (OS) and progression-free survival (PFS).

Results

After the median 16.6 months of follow-up, the unfavorable EGFR rs2293347AA or GA genotype was significantly correlated with shorter OS (AA vs. GG: 2.0 vs. 21.0 months; hazard ratio (HR) = 2.44, 95% confidence interval (CI) = 1.06–5.56; P = 0.036; GA vs. GG: 15.0 vs. 21.0 months; HR = 1.75, 95%CI = 1.08–2.86, P = 0.025) compared with the favorable rs2293347GG genotype. The prognostic significance of EGFR rs4947492 polymorphism on OS also existed (GG carriers vs. AA carriers: median OS = 24.6 vs. 14.9 months, HR = 0.29, 95%CI = 0.10–0.83, P = 0.021). No significant associations were found among other EGFR SNPs and survival.

Conclusion

EGFR rs2293347 and rs4947492 SNPs might be potential predictive markers of OS in advanced lung adenocarcinoma patients treated with Gefitinib.     

Metaplastic breast cancer: Treatment and prognosis by molecular subtype

BackgroundMetaplastic breast cancer (MBC) is a rare and aggressive subtype of breast. However, the effect of molecular subtype on treatment and prognosis of MBC remains unclear.Patients and methodsThe Surveillance, Epidemiology, and End Results database was used to analyze patients with MBC between 2010 and 2016. Molecular subtype was stratified to TN group (ER and PR-/HER2-), HER2 group (ER and PR-/HER2+, ER/PR+ and HER2+), and HR group (ER/PR+ and HER2-). The breast cancer-specific survival (BCSS) differences were estimated using multivariate Cox regression model and Kaplan-Meier curves.ResultsWe included 1665 patients with median follow-up time of 27 months (range 0–83 months). 1154 (69.3%), 65 (3.9%), and 446 (26.8%) patients presented in TN group, HER2 group, and HR group, respectively. On multivariate Cox analysis, the prognosis was related to age, tumor size, regional node metastasis, and surgery. Molecular subtype remained no impact on BCSS. Radiotherapy (RT) was associated with better prognosis. Patients cannot benefit from chemotherapy. In Kaplan-Meier curve, triple-negative (P = 0.047) and HR-positive (P = 0.006) patients receiving RT had a superior BCSS than that not RT. HER2-positive patients cannot benefit from RT. However, adjusted Kaplan-Meier survival model showed that triple-negative (P = 0.019) but not HER2-positive (P = 0.575) or HR-positive (P = 0.574) patients receiving RT had a superior BCSS than that not RT.ConclusionsMolecular subtype is not associated with the better prognosis of MBC. Patients could benefit from RT. However, triple-negative but not HR-positive or HER2-positive patients have superior survival after receiving RT.     

Cryoprotective therapy for hepatocellular carcinoma: Study of 51 patients with a single lesion

Percutaneous cryoablation is a potentially curative treatment for hepatocellular carcinoma (HCC). After liver cryosurgery, rapid elevations of transaminases and bilirubin are common, but are usually transient and normalize within a few days. This study retrospectively reviewed clinical data from 51 patients who underwent liver cryoablation in our hospital during the past 4.5 years. Sixty-six percutaneous cryoablations were performed in these patients and transaminase and bilirubin levels before and after the procedure were observed. Although most patients received liver-protective treatment before cryosurgery, transaminase levels were double (mean alanine transaminase (ALT) and aspartate transaminase (AST) were 71 U/L and 85 U/L, respectively) the normal ranges in our hospital. One day after cryosurgery, ALT and AST had increased 3.3-fold (peak mean was 241 U/L) and 5-fold (peak mean was 427 U/L), respectively, but were close to the preoperative level 5 days post-cryosurgery. No significant increase of serum bilirubin was observed. Serum transaminase and bilirubin levels were compared between hepatitis B positive and hepatitis B negative patients. Only in the hepatitis B positive group were total bilirubin (74 μmol/L/23 μmol/L = 3.2) and direct bilirubin (45 μmol/L/12 μmol/L = 3.8) more than 3 times the preoperative level 7–9 days after treatment. Overall, ALT and AST are valuable as indicators of liver function impairment following cryosurgery. In patients with hepatitis B virus, serum bilirubin was 3 times the preoperative level 7–9 days after cryosurgery. Liver-protective treatment may alleviate liver function impairment due to cryosurgery.     

Treatment of central type lung cancer by combined cryotherapy: Experiences of 47 patients

Most patients with central type lung cancer (CTLC) are not candidates for surgery; systemic chemotherapy and external beam radiotherapy are the main treatments but have not greatly affected patient outcome. Combined percutaneous and endobronchial cryotherapy has been used successfully to treat CTLC; this study aimed to determine its feasibility and safety. Forty-seven patients with unresectable CTLC (22 endotracheal, 26 tracheal wall and 21 extratracheal tumors) underwent 69 sessions of combined percutaneous cryosurgery, endobronchial cryosurgery and airway stenting. The long diameter of all tumors was <5 cm. Biopsy showed non-small cell lung cancer (NSCLC) in 40 patients (medium or well differentiated in 20 cases, poorly differentiated in 20) and small cell lung cancer (SCLC) in seven. Within 3 days after treatment, ventilatory capacity and performance status had obviously increased and cough, signs of dyspnea, hemoptysis and atelectasis improved significantly, but symptoms of pneumothorax and pleural effusion emerged. After 2 weeks, all complications had disappeared completely, as had cough. Progression-free survival (PFS) for endotracheal tumors (8 ± 4 months) was shorter than that for tracheal wall (13 ± 6 months, P < 0.05) and extratracheal (14 ± 8 months, P < 0.01) tumors. The PFS of NSCLC (11 ± 5 months) was significantly longer than that of SCLC (4 ± 2 months, P < 0.0001). The PFS of medium or well differentiated CTLC (15 ± 8 months) was significantly longer than that of poorly differentiated CTLC (7 ± 3 months, P < 0.0001). In conclusion, combined cryotherapy is a safe and effective treatment for CTLC, with PFS largely influenced by tumor location and pathologic type.     

Percutaneous ultrasonography and computed tomography guided pancreatic cryoablation: Feasibility and safety assessment

Objective

To assess the safety and feasibility of percutaneous cryoablation on pancreatic cancer via ultrasonography (US) and computed tomography (CT) guidance.

Materials and methods

This retrospective review was approved by the institutional review board and of informed consent. Thirty-two patients (18 men and 14 women; median age 62; age range, 30–77 years) with pancreatic cancer (stage II/III/IV, 3/11/18) treated with percutaneous US and CT guided cryoablations between February 2009 and February 2010 were eligible for this review. Thirteen tumors in pancreatic head and 19 in pancreatic body and/or tail measuring 2–11 cm (mean, 5.2 cm ± 8 [standard deviation]) were ablated with 49 procedures in total. Feasibility was analyzed by enhanced CT 1–3 months post procedure and safety was assessed by clinical signs, symptoms and laboratory results.

Results

Neither procedural death nor serious complications occurred. Fifteen tumors (46.9%) smaller than 5 cm were successfully ablated by one session of cryoablation. Twenty-seven patients experienced a ?50% reduction in pain score, 22 experienced a 50% decrease in analgesic consumption and 16 experienced a ?20 increase in Karnofsky Performance Status (KPS) Score. Partial response (PR) and stable disease (SD) turned up in 9 and 21 patients, respectively, lesions in whom were identified controlled by none enhancement on enhanced CT. Mean and median survival was 15.9 and 12.6 months, respectively. The 6-, 12- and 24-month survival rates were 82.8%, 54.7% and 27.3%, respectively.

Conclusion

US and CT guided percutaneous cryoablation is a safe and promising local treatment for pancreatic cancer.     

Effects of locoregional radiotherapy in de novo metastatic nasopharyngeal carcinoma: A real-world study

BackgroundTo evaluate the value of locoregional radiotherapy (LRRT) in de novo metastatic nasopharyngeal carcinoma (dmNPC) and identify predictive factors for additional LRRT after palliative chemotherapy (PCT).MethodsOverall survival (OS) was the primary endpoint. Patients who underwent PCT and LRRT were categorized as the PCT+LRRT group; patients who only received palliative chemotherapy were categorized as the PCT group. Oligometastatic diseases (OMD) was defined as ≤5 metastatic lesions and ≤2 metastatic organs.ResultsA total of 168 patients were included for this study. The median OS of patients in the PCT+LRRT group was significantly higher than those in the PCT group (57 months vs. 22 months, P<0.001). Multivariate analyses (MVA) showed that LRRT (HR=0.533, 95% CI: 0.319–0.889, P = 0.016) and OMD (HR=0.548, 95% CI: 0.331–0.907, P = 0.019) were independent prognostic factors for dmNPC. Furthermore, Kaplan–Meier analyses showed that the 3-year OS of patients who received LRRT was significantly better than those who did not receive LRRT in the OMD subgroup (66.3% vs. 25.2%, P<0.001). While, the 3-year OS of patients who received LRRT and without LRRT was no different in the polymetastatic disease (PMD) subgroup (38.9% vs.11.5%, P = 0.115). MVA showed that LRRT was a favorable prognosticator in the OMD subgroup (HR=0.308, 95% CI: 0.159–0.598; P<0.001), and not a favorable prognosticator in the PMD subgroup (HR=0.510, 95% CI: 0.256–1.014, P = 0.055).ConclusionsLRRT has the potential to prolong OS in NPC patients with de novo OMD. These results suggest that OMD is a potential indicator for filtering beneficiaries from LRRT.     

Comprehensive treatment of malignant mesothelioma patients after the failure of systemic chemotherapy

Malignant mesothelioma (MM) is an aggressive neoplasm usually arising from the mesothelial surfaces of the pleural or peritoneal cavity. Currently, no standard therapy is available. The most commonly used therapy is cytoreductive surgery combined with systematic chemotherapy, but the median overall survival (OS) is less than 12 months; moreover, treatments are lacking for patients in whom chemotherapy has failed and/or who cannot withstand surgery. We investigated multiple minimally invasive therapies (cryosurgery, photodynamic therapy and intracavity chemotherapy) for the treatment of MM patients in whom systemic chemotherapy had failed. Twenty-seven patients were divided into comprehensive (combination of the three therapies) and palliative (intracavity chemotherapy only) treatment groups. The OS of patients who received comprehensive treatment was significantly longer than that of those who received palliative treatment (median OS: 64 vs. 9 months, P < 0.001). This interesting result was not associated with treatment timing, but was closely associated with repeated treatments.     

The treatment of paravertebral malignant mesenchymal tumor pain with cryoablation

Objective

The purpose of this study was to evaluate the feasibility, safety, and efficacy of cryoablation to treat pain from paravertebral malignant mesenchymal tumors.

Method

Cryoablation was performed on 15 patients who suffer from unresectable painful paravertebral malignant mesenchymal tumors and whose pain was poorly controlled by conventional treatment methods. The sizes of the tumors varied from 3 to 20 cm. The patients’ pain at baseline before the cryoablation and the pain they felt 1 day, 1 week, 1 month, and 3 months after the cryoablation were assessed respectively by the Brief Pain Inventory (BPI).

Result

BPI scores are divided into two categories: the influence of pain and the severity of pain. Both results showed a decline after the cryoablation. The evaluation score of pain severity decreased significantly (P = 0.001, P = 0.031) on the observation of 1 day and 1 month after the cryoablation; that of pain influence decreased significantly (P = 0.016, P = 0.036) in the cases of 1 day and 1 week after cryoablation. Two patients (13.33%) had mild complications, but no serious complications occurred.

Conclusion

Cryoablation is a low risk, well-tolerated topical treatment for the pain of patients with unresectable paravertebral malignant mesenchymal tumor.     

Alleviating the pain of unresectable hepatic tumors by percutaneous cryoablation: Experience in 73 patients

Pain caused by liver tumors can be alleviated by cryoablation, but little is known about the analgesic effects and duration of pain alleviation. We retrospectively reviewed the changes in the severity of pain before and after percutaneous cryoablation of hepatic tumors. Each patient enrolled in this study had a single hepatic tumor; patients with large tumors (major diameter, ?5 cm) underwent transarterial chemoembolization (TACE) first and then cryoablation. Severe abdominal pain that was not controlled with long-lasting oral analgesics was treated with opioid injections. In all 73 study patients, severe abdominal pain was gradually eased 5 days after cryosurgery, completely disappeared after 15 days and did not recur for more than 8 weeks. There were no differences in analgesic effects between patients with hepatocellular carcinomas and those with liver metastasis (P > 0.05). The patients were divided into four groups depending on their pain outcomes: (i) immediate relief (n = 6), severe abdominalgia was no longer present after cryosurgery; (ii) delayed relief (n = 11), severe abdominalgia disappeared gradually within 15 days after the cryosurgery; (iii) always pain-free (n = 39), severe abdominalgia was not present before or after treatment; and (iv) new pain (n = 17), abdominalgia developed after treatment and disappeared within 15 days. In summary, percutaneous cryoablation of hepatic tumors caused short-term pain in some patients, but this pain disappeared within 15 days. Moreover, the pain-relieving effect of this treatment was sustained for at least 8 weeks, without severe side effects.     

Morphology of hypoxia following cryoablation in a prostate cancer murine model: Its relationship to necrosis, apoptosis and, microvessel density

The aim of this study is to investigate the tumor tissue changes in terms of hypoxia and demonstrate its relationship to vascularity and apoptosis following therapeutic cryoablation in a prostate tumor murine model. Total 67 male C57BL/J6 mice were assigned into sham-operation group and cryoablation group. Murine prostate tumors (RM-9) were inoculated subcutaneously in a right hind leg and treated with cryotherapy. Of 30 mice, tumor volumes were measured for 12 days following operation. Of 37 mice, tumor tissues were harvested in 24 h following operation, and histological/molecular changes were analyzed. Hematoxylin and eosin or immunohistochemical staining were utilized to quantify tumor necrosis, hypoxia (pimonidazole), vascularization (CD31), and apoptosis (cleaved caspase-3). The results showed that cryoablated tumors demonstrated significant delayed growth following treatment compared to controls. Pathological analysis revealed that the severity of hypoxia increased in the cryoablation arm compared to controls. Necrotic and apoptotic populations were also found to be increased in the cryoablation arm (P = 0.028 and 0.021). Hypoxia demonstrated a positive correlation with necrosis (r = 0.520, P = 0.001) and apoptosis (r = 0.474, P = 0.003), while showing negative correlation with microvessel density (MVD) (r = −0.361, P = 0.021). We concluded that in the peripheral areas from the cryoneedle impact site, strong hypoxic responses were found, which may play important role in tumor freezing injury. To our knowledge, this is the first report describing cryoablation-mediated changes of hypoxia at a molecular level in the prostate cancer murine model.     

Comparison of a Concurrent Fluorouracil-Based Regimen and a Taxane-Based Regimen Combined with Radiotherapy in Elderly Patients with Esophageal Squamous Cell Carcinoma

Elderly patients with esophageal carcinoma may benefit from concurrent chemoradiotherapy (CCRT). However, the optimal concurrent chemotherapy regimen has not been determined. The aim of our study was to assess the efficiency and tolerance of treatment with a concurrent 5-fluorouracil (5-Fu)–based regimen and a taxane-based regimen combined with radiotherapy in elderly patients with esophageal squamous cell carcinoma (ESCC). A total of 46 patients with ESCC aged older than 65 years were included in this study. The patient population was divided into two treatment groups: 24 patients who received CCRT with a 5-Fu–based regimen were allocated to the PF group, and 22 patients who received CCRT with a taxane-based regimen were allocated to the DP group. The median overall survival (OS), median progression-free survival (PFS), overall response rate, and treatment-related toxicity were assessed. For patients in the PF group, the median OS time was 27.8 ± 9.1 months, and the median PFS time was 12.5 ± 2.7 months. Patients in the DP group had comparable survival outcomes, with a median OS time of 34.4 ± 6.4 months and a median PFS time of 21.1 ± 6.4 months (P = .296 and P = .115, respectively). Grade ≥3 leukocytopenia and grade ≥2 anemia occurred in 63.6% and 59.1% of patients in the DP group, respectively, and in 25.0% and 16.7% of patients in the PF group, respectively. Our results suggest that CCRT with a taxane-based regimen results in a higher incidence of treatment-related toxicity than CCRT with a 5-Fu–based regimen but comparable survival outcomes.     

Second-Line Treatment of Her2-Positive Metastatic Breast Cancer: Trastuzumab beyond Progression or Lapatinib? A Population Based Cohort Study

Background

The relative efficacy of lapatinib vs. continuing trastuzumab beyond progression (TBP) in HER2-positive metastatic breast cancer (MBC) patients, who progressed on first-line trastuzumab, is still unclear. The objective of this population based cohort study was to compare outcomes of lapatinib vs. TBP in daily practice.

Methods

All HER2-positive MBC patients who began second-line anti HER2 therapy between 1st January 2010 and 30th August 2013 were selected from Clalit Health Services’ (CHS) electronic database. Available data on patient and disease characteristics and treatments were analyzed. The primary endpoint was overall survival (OS). Outcomes were compared using the Kaplan-Meier (log-rank) method and Cox proportional hazards model.

Results

64 patients received second-line lapatinib and 93 TBP. The two treatment groups were similar in age and co-morbidity rates, but differed in proportion of prior adjuvant trastuzumab (lapatinib: 29.7%, TBP: 16.1%, P = 0.043) and rates of prior brain metastases (lapatinib: 32.8%, TBP: 10.8%, P = 0.01). Lapatinib median OS was 13.0 months (95% CI: 9.5–16.5) vs. 31.0 for TBP (95% CI: 20.6–41.4), P<0.001. On multivariate analysis, longer OS was preserved for TBP, after controlling for differences in age, adjuvant trastuzumab, duration of first-line trastuzumab therapy, brain metastases, visceral metastases and hormonal treatment [Hazard Ratio (HR) = 0.63, 95% CI: 0.40–0.99, P = 0.045].

Conclusion

In this comparative cohort study, OS of HER2-positive MBC patients treated with TBP was significantly longer than with lapatinib. These results might be especially relevant in settings where ado-trastuzumab-emtansine (TDM-1), the current preferred agent in this setting, is not available yet for patients.