Prognostic factors of survival in patients treated with nab-paclitaxel plus gemcitabine regimen for advanced or metastatic pancreatic cancer: A single institutional experience.

The objectives of this study were to evaluate the effectiveness of nab-paclitaxel plus gemcitabine (NAB-P/GEM) regimen in an unselected population of patients with advanced inoperable or metastatic pancreatic cancer (PC), and to identify the prognostic factors influencing overall survival (OS). EXPERIMENTAL DESIGN: Patients with age < 85 years, ECOG-performance status (PS) < 3, and adequate renal, hepatic and hematologic function were eligible. NAB-P (125 mg/m2) and GEM (1000 mg/m2) day 1,8,15 every 4 weeks were employed for 3-6 cycles or until highest response. RESULTS: Overall, 147 cycles (median 4, range 1-11 cycles) were administered on thirty-seven consecutive patients (median 66 years old, range 40-82) treated. The median overall progression-free survival and OS were 6.2 and 9.2 months, respectively. The G 3-4 dose-limiting toxicity were neutropenia (20.7%), severe anemia (17.2%), and cardiovascular toxicity (10.3%). PS, number of cycles, baseline CA 19-9 and LDH serum levels, were found to be significantly related to OS. The multivariate analysis showed that both number of cycles (HR = 9.14, 95% CI 1.84-45.50, p = 0.001) and PS (HR = 13.18, 95% CI 2.73-63.71, p = 0.001) were independently associated with OS. CONCLUSION: NAB-P/GEM regimen should be used in all patients with advanced or metastatic PC, with the exception of those with serious contraindications to chemotherapy, such as severe renal or hepatic impairment or major cardiovascular diseases

Adjuvant hormonal therapy in women with early-stage breast cancer

For decades, adjuvant hormonal therapy has become the standard treatment of patients with estrogen receptor-positive breast cancer. Currently, the drugs available are GnRH agonists, selective estrogen receptor modulators, and aromatase inhibitors. The use of GnRH agonists represents a potentially reversible treatment that can restore ovarian function after chemotherapy. In premenopausal women, systemic therapy based on selective estrogen receptor modulators administration (e.g., tamoxifen) usually represents the standard adjuvant treatment. There are not sufficient data to recommend the routine addition of GnRH agonists to other endocrine therapies. In postmenopausal women, the disease-free survival was significantly prolonged in patients treated with aromatase inhibitor compared with those treated with tamoxifen, but the survival benefit was modest. Better results were obtained when the two drugs were administered sequentially. According to the ASCO guidelines, after 5 years of tamoxifen treatment, either tamoxifen or aromatase inhibitors therapy should be suggested for an additional 5 years. Unfortunately, most adverse events are consistent with estrogen deprivation and are common to all therapies, and the cumulative toxicity causes discontinuation and nonadherence to therapy in up to 50% of patients. Switching tamoxifen to an aromatase inhibitor may reduce adverse event incidence. Molecular-targeted therapy is useful in patients with advanced, relapsed or hormonal therapy-resistant tumors, usually as second- or third-line treatment. These drugs are usually added to aromatase inhibitors; however, currently, they have not yet been used in patients with early breast cancer

Prognostic factors for survival in patients with breast cancer and liver metastases.

In patients with breast cancer (BC) the liver is one of the site of distant metastases, accounting for about 15% of patients. Isolated liver metastases (LMs) are uncommon, and the presence of extra-hepatic disease usually represents a contraindication to liver resection. Liver metastasis of BC origin is usually life limiting, and the patient needs treatment. Surgical resection of parts of the liver is considered the only potentially curative therapy, but unfortunately only few patients are suitable for liver resection. The 5-year survival of patients with LMs from colorectal cancer ranges from 20% to 25%, while the survival period after resection to manage LMs from BC is unclear, due to the limited number of studies, ranging between 36-42 months. The aims of this study was to identify factors predictive of survival of women with LMs from BC who underwent liver resection, and to evaluate possible relationship between survival, age, primitive tumor size, number of LM, CA 15-3, ER and PR rate. The medical charts of 11 women (median age 57 years, range 39-67 years) with LM and no evidence of extra-hepatic disease who had undergone curative surgery for BC were reviewed retrospectively. All patients received 6-12 cycles of neoadjuvant chemotherapy (anthracyclines) alone or chemotherapy plus hormone therapy (tamoxifen or aromatase inhibitors) prior to liver resection (wedge resection or segmentectomy), and those with disease progression were excluded. All LMs were metachronous, 7 patients had a single LM, 3 had two LMs, and 1 had three LMS. The baseline data were: size of the primitive BC=25.8\ub16.4 mm, number of LMs=1.4\ub10.68, ER=46.6\ub133.8%, PR=48.3\ub134.2%, CA15-3=84.7\ub133.1 U/mL. The median survival rate was 32 months (range 12-77 months). As expected, there was a significant correlation between ER and both PR (R=0.95, p< 0.001) and CA 15-3 (R=0.64, p=0.034), and between CA 15-3 and both PR (R=0.67, p=0.024) and number of LMs (R=0.69, p=0.017). At univariate analysis younger age, number of LMS, and size of the primitive tumor were associated with poorer prognosis, while at multivariate analysis only the age (R=0.81, p=0.002) of the patients was an independent factor of survival. In conclusion, the survival of patients with BC and LMs is independent of hormone-receptor status and serum CA 15-3 levels at the time of liver resection

Carboxy-terminal telopeptide (CTX) and amino-terminal propeptide (PINP) of type I collagen as markers of bone metastases in patients with non-small cell lung cancer.

The early diagnosis of non-small cell lung carcinoma (NSCLC) is difficult, and 30-40% of patients with NSCLC develop bone metastases (BMs) during the course of their disease. Because the delayed demonstration of skeletal involvement may seriously affect survival, there is a need for early diagnosis of BMs. Unfortunately, the sensitivity of common serum tumor markers is low and they are used mainly for monitoring the efficacy of therapy and detection of recurrence. The aim of this study was to evaluate the utility of a panel of serum biomarkers in patients with NSCLC and BMs. Sixteen patients (11 males, five females; median age=64 years, range 54-68 years) with NSCLC and BMs (cases), and 18 age- and stage-matched patients without BMs (controls) underwent measurement of serum carboxy-terminal telopeptide of type I collagen (CTX), tartrate-resistant acid phosphatase isoform type 5b (TRAP5b) and amino-terminal propeptide of type I collagen (PINP), carcinoembryonic antigen (CEA) and fragments of cytokeratin 19 (CYFRA 21-1. CTX (443.7\ub1945.1 vs. 402.7\ub128.4 pg/ml, p=0.003) and PINP (75.9\ub111.4 vs. 64.1\ub17.5 \u3bcg/l, p=0.001) were significantly higher in patients with BMs, while the mean value of the other markers did not differ (p=NS) between cases and controls. The sensitivity, specificity and accuracy were 73.3%, 86.7% and 79.4% for CTX; 55.5%, 62.5% and 58.8% for CEA; 65.0%, 78.6% and 70.6% for CYFRA; 30.4%, 76.2% and 67.6% for TRAP5b; and 72.2%, 81.2% and 76.5% for PINP, respectively. The area under the receiver operating characteristic curve (AUC) for CTX was 0.68. In conclusion, CTX and PINP measurement can be useful in monitoring patients with NSCLC during follow-up, with the aim of detecting BMs early

Prognostic significance of circulating tumor cells in patients with colorectal cancer and liver metastases.

BACKGROUND: Despite the reduction in colorectal cancer (CRC) incidence rates in recent years, this tumor remains the most common gastrointestinal cancer in Western countries. CRC is a systemic disease (stage IV) in about 20% of patients, and metastases are most commonly found in the liver and lung. Unfortunately, patients undergoing surgery for CRC liver metastases are at risk for tumor recurrence. Several prognostic criteria have been proposed to improve patient selection for liver resection and adjuvant or neoadjuvant chemotherapy, including specific molecular or genetic assay and circulating tumor cells (CTC) dissemination detection. CTC can be revealed by reverse transcription-polymerase chain reaction (RT-PCR) based on mRNA detection. Since blood contains RNAse able to rapidly destroy extracellular RNA, the detection of mRNA can be accepted as an indicator of the presence of CTC. The aim of this study was to evaluate whether the presence of CTC in blood may predict tumor recurrence in patients who underwent resection for CRC liver metastases (LMs). The Fisher exact probability test, relative risk (RR) and associated 95% confidence interval (CI) calculation were used to analyze results. PATIENTS & METHODS: Preoperative blood samples were obtained form 12 patients (8 men, 4 women, median age 67 years, range 58-72 years) with stage IV CRC and LMs. Blood samples were examined by immunomagnetic enrichment with RT-PCR technique based on specific molecular biological markers to detect CTC. The results were expressed as CTC-positive or CTC-negative samples. Patients underwent both spiral CT-scan and MRI to better define the size e number of metastases. CT-scan of the chest and whole-body 99mTc-MDP scintigraphy were also performed to exclude pulmonary and bone metastases, respectively. 18F-FDG-PET was used only in selected patients. Intraoperative ultrasound of the liver was performed in all patients. The chi-square test was used to analyze results. RESULTS: Nine patients showed CTC positivity, while three were CTC-negative. At 12-month follow-up, 9 patients developed relapse of the disease (CTC-positive=8, CTC-negative=1), and 3 were disease-free (CTC-positive=1, CTC-negative=2). A significant relationship between CTC-positivity and recurrence (chi-square=3.7, p=0.05) was found. The risk ratio (RR) was 2.66 (95%CI 0.53-13.43). CONCLUSIONS: In patients with CRC and LMs who underwent surgery, CTC detection by RT-PCR represents a reliable tool for selecting those at risk of relapse, and should be suggested in all patients with advanced CRC

Risk factors for lung metastases from invasive ductal breast carcinoma. A case-control study at five-year follow-up in a population of women who underwent curative surgery

Background: Breast cancer (BC) accounts for about one-third of cases of cancer in women. BC occurs predominantly in elderly women, continue to be one of the most common causes of cancer death, and mainly metastasizes to the skeleton and lung. Although complete excision of primary tumor improves survival in patients with advanced metastatic disease, pulmonary metastasectomy plays a role in the management of patients. However, patients with small metastasis have a better overall survival, and thus the early detection of lung metastases (LM) is crucial. Indeed, in several studies, risk factors (RFs) such as age, stage of the disease, serum tumor markers, and other biological parameters obtained from pathological specimen, have been evaluated. The aim of this study was to analyze their role in differentiating patients at risk of having LMs among a cohort of women with BC. Patients and methods: We retrospectively reviewed data regarding a series of 348 women (median age 60 years, range 28-85) who underwent curative surgery for pT1-2, N0-1 (stage I and IIA) invasive ductal breast carcinoma. During five-year follow-up, 15 (4.3%) patients developed LMs (cases), and 39 (11.2%) other type of cancer relapse, while 294 (84.5%) were disease-free (controls). The followings parameters were considered: age of the patients, size of the tumor (T), axillary lymph node (AN) status (N), estrogen (ER) and progesterone (PR) receptor negativity, human epidermal growth factor receptor 2 (HER2) and nuclear antigen Ki67 overexpression, adjuvant chemotherapy. Odds ratio (OR) estimates and the associated 95% confidence interval (CI) were obtained, and the significance level was set at p<0.01. Results: Age2 cm (T2) (OR=2.90, 95% CI 1.02-8.27, p=0.041), and ER negativity (OR=3.51, 95% CI 1.21-10.17, p=0.018) were weak RFs, while PR negativity (OR=2.01, 95% CI 0.70-5.73, p=0.14), HER2 (OR=1.48, 95% CI 0.49-4.49, p=0.32) and Ki67 (OR=1.72, 95% CI 0.59-4.99, p=0.23) overexpression, and no chemotherapy administration (OR=1.06, 95% CI 0.35-3.20, p=0.55) were independent of LMs onset

Urokinase-type plasminogen activator and inhibitor as prognostic markers in patients with non-small cell lung cancer and lymph node metestases

Background: Several biological markers have shown their usefulness in patients with lung cancer. Urokinase-type plasminogen activator (u-PA) is a member of the serine protease, an extracellular matrix protease strictly related to tumor aggression. It is localized on the tumor cells surface by binding to a specific receptor (u-PAR), which regulates the proteolytic activity around the cells. Plasminogen activator inhibitor 2 (PAI-2) regulates the u-PA activity. The expression of u-PA and PAR is elevated in malignant tumors, while low levels of PAI-2 expression correlates with the presence of metastases. We retrospectively assayed the expression of u-PA, u-PAR, and PAI-2 in specimens from non-small cell lung carcinoma (NSCLC), with the aim of evaluating possible relationship between these prognostic markers and the presence of lymph node metastasis. Patients and methods: Paraffin-embedded archival tumor tissues from 59 patients with NSCLC were used to assess by immunohistochemical staining expressions of u-PA and u-PAR, and to measure by enzyme-linked immunosorbent assay levels of PAI-2 antigen. The analysis was performed by reverse transcriptase polymerase chain reaction (RT-PCR). Patients were 42 (71.2%) males and 17 (28.8%) females, with a median age of 62 years (range 54-68). LN metastases were found in 25 (42.3%, Group A) patients, while 34 (57.7%, Group B) were node-negative (pN0). A positive-staining area of more than 10% was considered as a positive result. The Pearson chi-square (\u3c72) test was used to compare data. Results: Positive markers (A vs. B) were found in 15 of 25 vs. 24 of 34 (u-PA), 10 of 25 vs. 24 of 34 (u-PAR), and 13 of 25 vs. 23 of 34 (PAI-2) specimens, respectively. A significant relationship between u-PAR positivity and LN metastasis (\u3c72=5.52, p=0.018) was found, while both u-PA (\u3c72=0.72 p=0.39) and u-PAR PAI-2 (\u3c72=1.48, p=0.22) were not related to LN status. Conclusions: In patients with NSCLC, u-PAR seems to be the key molecule for extracellular matrix degradation enzyme and the target molecule of cancer metastasis prevention, representing a sensitive marker of prognosis

Ultrasonic dissection system technology in breast cancer: a case-control study in a large cohort of patients requiring axillary dissection

In the sentinel node era, axillary dissection (ALND) for breast cancer (BC) is required much less frequently than in the past. However, complications, such as prolonged drainage output and seroma formation, are still observed. Harmonic dissection devices (HDDs) are widely used in laparoscopic and minimally invasive surgery to reduce collateral damage during tissue dissection, but its usefulness in breast surgery is unclear. The aim of this study was to evaluate the efficacy of HDDs compared to that of conventional dissection in performing ALND. One hundred thirty-nine women (median age 61 years, range 34-71 years) with confirmed pT1-2 primary infiltrating ductal BC undergoing curative surgery were enrolled in the study. The population was prospectively randomized between two age- and stage-matched arms: group A (cases)-68 (48.9 %) patients (HDD technique), versus group B (controls)-71 (51.1 %) patients (conventional technique). In group B, skin flaps were obtained using a scalpel, scissors, and electrocautery which was never used for ALND. In group A, for each operation time, the HDDs were used exclusively. The mean operative time, intraoperative blood loss, and drainage output were (A vs. B) 95 +/- A 22 versus 109 +/- A 25 min, 56 +/- A 12 versus 86 +/- A 15 mL, and 412 +/- A 83 versus 456 +/- A 69 mL, respectively (p < 0.01). Twenty-nine (20.9 %) patients developed an axillary seroma: 9 (13.2 %) and 20 (28.2 %) for groups A and B, respectively (p = 0.030). Our study confirms that in patients with BC requiring ALND the use of HDDs is more time efficient than conventional surgery, and reduces intraoperative bleeding, the amount of drainage, and the risk of seroma formation. These results may lead to several short- and long-term advantages. Thus, a careful evaluation of the cost-benefits of nontraditional tools, such as HDDs, should be performed in all patients undergoing modified radical or partial mastectomy and ALND for BC