Ribociclib therapy in peritoneal carcinomatosis secondary to HER2-negative metastatic breast cancer: A clinical case with a positive outcome.

Although metastatic breast cancer can be fatal, a series of randomized double-blind placebo-controlled phase 3 trials (MONALEESA studies) have shown that ribociclib is an effective anticancer drug for the treatment of advanced breast cancer with bones, liver, lungs, and brain as major metastatic sites. Here, we report the clinical case of a woman with peritoneal carcinomatosis secondary to HER2-negative estrogen receptor-positive breast cancer successfully treated with ribociclib and letrozole. After 9-month follow-up, total body computed tomography imaging showed resolution of hypodense areas surrounding the hepatic hilus with concomitant reduction in both bile duct dilatation and peritoneal effusion, and abdominal lymphadenopathy was excluded. Notably, therapy was well tolerated throughout the treatment with no side effects.

Early Docetaxel and Androgen Deprivation in the Treatment of Metastatic, Hormone-sensitive Prostate Cancer.

BACKGROUND: To assess the role of docetaxel plus androgen deprivation in metastatic, hormone- sensitive prostate cancer. METHODS: A qualitative systematic review of literature was performed. All the randomized phase III trials comparing docetaxel plus androgen deprivation with androgen deprivation alone in patients with metastatic, hormone-sensitive prostate cancer were considered eligible and included into the analysis. RESULTS: Six papers (3 randomized clinical trials, and 3 systematic reviews with meta-analysis) were considered eligible and included into the analysis. A significant improvement in time to progression and OS in the entire population treated with docetaxel plus androgen deprivation was reported in all the trials and meta-analyses, and in two trials and all meta-analyses, respectively. One trial reported improvement of OS only in patients with high volume disease, and the meta-analysis that also analyzed the subgroups of patients with high or low volume disease reported a benefit of docetaxel plus androgen deprivation for either the entire population or the two subgroups of patients. CONCLUSION: The early use of docetaxel combined with androgen deprivation improves the main outcomes in the treatment of metastatic, hormone-sensitive prostate cancer. The available data suggest that docetaxel plus androgen deprivation could be considered the novel standard for fit patients with metastatic, hormone-sensitive prostate cancer.

Early Palliative Care in Advanced Oncologic and Non-Oncologic Chronic Diseases: A Systematic Review of Literature.

BACKGROUND: To assess the role of early palliative care in patients with advanced oncologic and non-oncologic chronic diseases. METHODS: A qualitative systematic review of literature was performed. All the randomized phase III trials comparing early, simultaneous palliative care and standard care in patients with advanced oncologic and non-oncologic diseases were considered eligible and included into the analysis. The outcomes were classified into 6 classes: quality of life, symptoms control, overall survival, quality of care, patients' and caregivers' satisfaction, and costs of the assistance. RESULTS: Twelve papers reporting the data of 9 trials were considered eligible and included into the analysis. Two nonrandomized trials were also included into the selection because of the methods used by the authors. The early, simultaneous approach was reported to improve quality of life in two out of 7 papers, symptoms control in 1 out of 5 papers, overall survival in 2 out of 3 papers, quality of care in 5 out of 8 papers, patients' or caregivers' satisfaction in 3 out of 4 papers; and to reduce the costs of assistance in 2 out of 3 papers. CONCLUSION: Early palliative care improves the main outcomes of the assistance in patients with advanced oncologic and non-oncologic chronic diseases. The available data are probably enough to consider early palliative cares a novel standard of care in these groups of patients.

Sunitinib therapy in metastatic papillary thyroid cancer.

We present the case of a 51-year-old woman with a follicular variant of papillary thyroid carcinoma. After surgery she experienced a relapse. Chemotherapy treatment led only to disease stabilization. In August 2009, we decided to start therapy with sunitinib 50 mg daily in an intermittent schedule (4 weeks on/2 weeks off). A CT scan after 3 months of treatment showed partial remission of disease according to the RECIST criteria. The patient continued sunitinib until January 2011, when CT evidenced progression in the mediastinal lymph nodes and pleura. Genetic analyses were carried out to determine if the clinical response in our patient was correlated with the presence of RET or BRAF mutations. No RET/PTC rearrangements or BRAF-V600E mutation, which are the two most common genetic alterations detected in papillary thyroid carcinoma, were found. It can be hypothesized that the activity of sunitinib in this patient was due to its antiangiogenic properties.

HER-3 status by immunohistochemistry in HER-2-positive metastatic breast cancer patients treated with trastuzumab: correlation with clinical outcome.

AIMS AND BACKGROUND: HER-3 signaling might contribute to resistance to trastuzumab. To clarify the role of HER-3 in HER-2-positive breast cancer, it is important to evaluate the level of HER-3 and its correlations with clinical outcome in metastatic breast cancer patients treated with trastuzumab. METHODS: HER-3 status by immunohistochemistry was evaluated in HER-2-positive metastatic breast cancer patients treated with trastuzumab-based therapy at our institution. Two scorings were utilized for interpreting staining for HER-3, and the correlation between HER-3 status and clinical outcome was evaluated. RESULTS: We evaluated HER-3 status in 61 of 76 HER-2-positive metastatic breast cancers treated with trastuzumab-based therapy at our institution from 4/1999 to 3/2006. We observed 55.2% objective responses; median time to progression and overall survival from start of trastuzumab therapy were 9.6 months (0.921-78.87) and 29.1 months (1.4-129.5+), respectively. With a cutoff of 50% staining tumor cells, we found 30 HER-3-negative and 31 HER-3-positive tumors. HER-3 status was not significantly associated with clinical outcome, but a shorter time to progression and overall survival were observed in patients with HER-3-positive tumors. CONCLUSIONS: HER-3 status by immunohistochemistry was not significantly associated with clinical outcome in HER-2-positive metastatic breast cancer patients. Further studies are necessary to evaluate the prognostic and predictive role of HER-3.

Biological markers and DNA flow cytometric analysis in radically resected patients with non-small cell lung cancer. A study of the Perugia Multidisciplinary Team for Thoracic Tumors.

AIMS AND BACKGROUND: The aim of this study was to evaluate the relationship between a panel of biological markers (p53, Bcl-2, HER-2, Ki67, DNA ploidy and S-phase fraction) and clinical-pathological parameters and its impact on outcome in non-small cell lung cancer (NSCLC). METHODS AND STUDY DESIGN: Tumor tissue specimens obtained after surgical resection were collected from consecutive patients with NSCLC. We used an immunocytochemical technique for p53, Bcl-2, HER-2 and Ki67 analysis in fine-needle aspirates obtained from surgical samples that were also evaluated by flow cytometric DNA analysis using a FACScan flow cytometer. RESULTS: From April 2000 to December 2005, 136 patients with radically resected NSCLC were recruited. Median age was 66 years (range, 31-84 years), male/female ratio 117/19, ECOG performance status 0/1 127/4, stage I/II/III 76/25/35, squamous/adenocarcinoma/large-cell/mixed histology 62/49/17/8, smokers yes/no 121/11. Positivity of p53, Bcl-2, HER-2 and Ki67 was detected in 51.4%, 27.9%, 25.0% and 55.8% of the samples, respectively; 82.9% of the cases revealed aneuploid DNA histograms and 56.7% presented an S-phase fraction of more than 12%. Statistically significant associations between high Ki67 and poorly differentiated tumors (P = 0.016) and a smoking history (P = 0.053); p53 positivity and high Ki67 (P = 0.002); HER-2 positivity and adenocarcinoma subtype (P = 0.015) and presence of lymph node involvement (P = 0.006); and Bcl-2 positivity and squamous cell carcinoma subtype (P = 0.058) were observed. At univariate analysis, high Ki67 proved to be the only marker associated with disease-free survival (P = 0.047). After adjusting for stage, none of the examined immunocytochemical markers emerged as an independent factor for disease-free and overall survival; only pathological stage was identified as an independent prognostic factor for disease-free survival (P = 0.0001) and overall survival (P = 0.0001). In the group of 76 patients classified as TNM stage I, high Ki67 was the only marker associated with recurrence of disease (P = 0.05). CONCLUSIONS: Our data do not support a relevant prognostic role of immunocytochemical markers in NSCLC, even if the Ki67 index might have particular relevance to identify patients with more aggressive tumors who are at high risk for disease relapse.

Plasma DNA, microsatellite alterations, and p53 tumor mutations are associated with disease-free survival in radically resected non-small cell lung cancer patients: a study of the perugia multidisciplinary team for thoracic oncology.

INTRODUCTION: This prospective study examined association between circulating plasma DNA, microsatellite alterations (MA), p53 mutations with time to relapse and survival in surgically treated non-small cell lung cancer (NSCLC) patients (pts). METHODS: Plasma samples, adjacent lung tissue, and lung tumor tissue specimens were collected from consecutive patients with stage I-III NSCLC. Blood samples of 66 matched healthy donors with positive smoking history were collected as controls. The plasma DNA amount was determined by real-time PCR. The analysis of MA at loci D3S1300, D3S1289, D3S1266, and D3S2338 on chromosome 3p was performed by radiolabeled PCR. p53 Mutations (exons 5, 6, 7, and 8) were detected by PCR-single-strand conformational polymorphism assay. RESULTS: There were 76 patients, 65 men; median age was 68 years (range, 42-86), 20 had stage I, 40 stage II, and 16 stage III, the majority of pts (48.7%) had squamous-cell histology. Sixty-nine (91%) were smokers and most had good Eastern Cooperative Oncology Group performance status (0/1:72/4). Mean circulating DNA of all pts was 60 ng/ml versus 5 ng/ml in smoker-matched controls (p < 0.0001). In pts without recurrence, mean circulating DNA was 48.5 ng/ml at baseline, 32.8 ng/ml at 3 month, and 20.6 ng/ml at 12 month after surgery. In pts with recurrence, mean circulating DNA at baseline was 97.1 ng/ml. At 3 month after surgery, mean DNA concentration was significantly lower in disease-free pts than in patients with recurrent disease (32.8 versus 292.7 ng/ml; p = 0.0016). MA in at least one locus was found in 39.5% of NSCLC tumors. p53 Genomic mutations were observed in 54.0% of tumor samples. Statistically significant associations were observed between MA and squamous-cell histotype (p = 0.007) and between p53 mutations and lymph node involvement (p = 0.012). MA and p53 mutations were found to be significantly associated with recurrence of disease (p = 0.033 and 0.026, respectively). CONCLUSION: Our results suggest that MA and p53 mutations in tumor DNA have a potential prognostic role for disease recurrence in NSCLC patients, and elevated levels of plasma circulating DNA identify patients with possible systemic disease at diagnosis. This might be proposed as an early detection test of disease recurrence.