Impact of systemic inflammatory markers in patients with ALK-positive non-small cell lung cancer treated with crizotinib.

OBJECTIVES: To evaluate the prognostic utility of inflammation-based prognostic scores in patients with ALK-positive metastatic or non-resectable non-small-cell lung cancer (NSCLC) treated with crizotinib. PATIENTS AND METHODS: A total of 82 patients with ALK-positive metastatic or non-resectable NSCLC who received ALK TKI crizotinib were included. Pre-treatment modified Glasgow prognostic score (mGPS), prognostic nutritional index (PNI), and systemic immune-inflammation index (SII) were calculated. Multivariable logistic regression and Cox proportional hazards models were used to assess the impact of pretreatment mGPS, PNI, and SII on overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). RESULTS: The ORR was 77.2%, while 1-year OS and PFS rates were 95.0% and 93.5%, respectively. The univariate analysis revealed significantly higher 1-year PFS (89.4 vs. 64.4%, p=0.043) and OS (92.0 vs. 83.3%, p=0.01) rates in patients with low (<934.7) vs. high (≥934.7) SII scores. Multivariate analysis revealed that PNI ≥0.09 was a significant determinant of poorer 1-year OS rates (hazard ratio [HR]: 2.46, 95% confidence interval [CI] 0.88-4.85, p=0.035). No significant difference was observed in survival rates according to gender, age, smoking status, prior lines of therapy, or mGPS scores, while higher mGPS scores (odds ratio [OR]: 0.1, 95%CI 0.16-1.04; p=0.009) and higher PNI scores (OR: 0.16, 95% CI 0.02-0.55; p=0.035) were associated with poorer ORR. CONCLUSION: Our findings indicate the prognostic significance of PNI and SII in terms of survival outcome and the impact of mGPS and PNI on treatment response in patients with ALK-positive NSCLC treated with crizotinib.

Factors predicting lapatinib efficacy in HER-2+ metastatic breast carcinoma: Does it work better in different histologic subtypes?

CONTEXT: Introduction of trastuzumab, a recombinant monoclonal antibody against the extracellular domain of HER-2, is a cornerstone in the treatment of HER-2+ breast carcinoma. However, many cancers that have an initial response to trastuzumab will progress some time later. After progression on trastuzumab-based first-line treatment, there are several options. Although TDM-1 (Trastuzumab emtansine) has prolonged progression-free survival (PFS) and overall survival in patients previously treated with trastuzumab and taxane, it is still not available in Turkey. Patients may be switched to lapatinib (an oral tyrosine kinase inhibitor targeting both HER-1 and HER-2), or they may re-challenge with trastuzumab. There is no clear definition of the patients who should be switched to lapatinib. AIM: In this study, we investigated the factors predicting the efficacy of lapatinib. SUBJECTS AND METHODS: Totally, 94 patients treated with lapatinib for metastatic breast carcinoma was included in our study. Retrospective data including pathology, treatments and treatment results, metastatic sites, and laboratory tests were collected. RESULTS: Progression-free survival was 9.1 months. Histologic subtypes other than invasive ductal carcinoma and liver metastasis were inversely related with PFS. Overall survival was 22.1 months, and patients with histologic subtypes other than invasive ductal carcinoma and who progress with brain metastasis had a worse prognosis. CONCLUSION: Clinicians should give attention to histologic subtype and metastatic sites when choosing patients for lapatinib treatment.

Sexual dysfunction in cancer patients: a review.

Cancer is a life-threatening disease despite the advanced therapeutic strategies now available. A common problem is that physicians and patients tend to concentrate on intensive medical treatment options and underestimate the treatment-related adverse effects. In this review, we summarize one of these adverse effects in cancer patients; sexual dysfunction (SD). In addition, current therapeutic choices with optimal doses and patient selection strategies are defined. All patients should be informed about problems associated with therapy-related SD and must be guided toward the most appropriate therapeutic options before starting treatment.

Survival analysis of metastatic colorectal cancer patients who were treated with the five major therapeutic agents over the course of disease.

PURPOSE: Exposure to all active agents may be more important than specific sequence of drug administration in the treatment of patients with metastatic colorectal cancer (mCRC). The purpose of this study was to evaluate the overall survival (OS) of mCRC patients who were treated with all 5 major therapeutic agents used in this malignancy. METHODS: We retrospectively reviewed the medical records of 395 mCRC patients referred to our clinic. The study included patients who received 5-fluorouracil (5-FU)-, irinotecan- or oxaliplatin-based chemotherapy and at least 3 cycles of bevacizumab and 4 weeks of cetuximab sequentially in various combinations. RESULTS: Forty mCRC patients received the 5 major therapeutic agents effectively and sequentially, and their mean OS was 26.43±2.04 months. The 3- and 4- year OS survival rates were 26.7% and 16.7%, respectively. When survival analysis was limited to the metastatic patients with at least 6 cycles of bevacizumab therapy in addition to standard duration of other chemotherapeutic agents (N=33), the mean OS was 26.7±2.38 months. With a further survival analysis limited to metastatic patients who were treated with at least both 6 cycles of bevacizumab and 8 weeks of cetuximab in addition to other therapies (N=17), the mean OS was 44.8±11.03 months. CONCLUSION: This study demonstrated that in mCRC patients there may be a significant survival advantage if an adequate tumor response was achieved with all major therapeutic agents. Therefore, we believe that we should treat our patients with the 5 major therapeutic drugs as effectively as possible.

Evaluation of the efficacy of adjuvant chemotherapy in patients with high-risk stage II colon cancer.

PURPOSE: This study aimed at comparing the disease-free survival (DFS) in high-risk TNM stage II colon cancer patients who had been subjected to adjuvant chemotherapy and TNM low-risk stage II patients who did not receive chemotherapy. METHODS: We retrospectively reviewed the medical records of stage II colon cancer patients between January 2006 and December 2011. High-risk patients were defined those with any colonic obstruction/perforation, mucinous histology, inadequate lymph node sampling, T4 disease, lymphatic/ vascular or perineural invasion, preoperatively elevated carcinoembryonic antigen (CEA) and high-grade tumor. All patients with high-risk features received adjuvant chemotherapy. RESULTS: There were 42 patients in the high-risk treatment group and 21 patients in the non-treatment (observation) group. There were no significant differences in terms of gender, tumor size, tumor localization, or the number of excised lymph nodes between the groups. The median follow- up time was 33.9 months in the treatment group and 29.3 months in the non-treatment group. Recurrence developed in 4 patients (6.3%), 3 of which were in the treatment group. DFS in both groups was statistically similar. CONCLUSION: Adjuvant chemotherapy in the high-risk patients resulted in similar DFS as that in the low-risk patients. Although the role of adjuvant chemotherapy for stage II colon cancer is unclear, it is rational to offer adjuvant chemotherapy to patients with high-risk stage II colon cancer.

Alveolar rhabdomyosarcoma originating from the uterine cervix.

Cervical alveolar rhabdomyosarcoma is a rare condition associated with poor prognosis. An 18-year-old patient presented with vaginal bleeding and a protruding mass from the vagina. Biopsy of the mass revealed alveoler rhabdomyosarcoma (ARMS), and radiological evaluation demonstrated that it originated from the uterine cervix. First, Wertheim's operation was carried out followed by four cycles of vincristine, actinomycine-D, ifosfamide (VAI) chemotherapy. However, the disease relapsed within three months, and the patient died of disease progression. Despite combination treatment, we could not achieve a desirable survival advantage in ARMS. Future studies may unveil the genomic profile of this rare condition, leading to invention of targeted therapies, which is the emerging trend in the treatment of sarcomas.

The prognostic value of thrombocytosis in newly diagnosed lung cancer patients: a retrospective analysis.

PURPOSE: The importance of thrombocyte count as a prognostic factor has not been adequately investigated in patients with lung cancer. We retrospectively examined the value of thrombocytosis as a prognostic factor and investigated its relationship with other clinicopathologic factors and survival. METHODS: The medical records of 260 patients with lung cancer were reviewed. Pretreatment thrombocyte count, histopathological diagnosis, disease stage, gender, age, performance status (PS), thrombotic episodes, weight loss and paraneoplastic syndromes were recorded. Overall survival (OS), progression-free survival (PFS) and disease-free survival (DFS) were evaluated in all patient subgroups. Thrombocytosis was defined as platelet count >400,000/µl. We assessed statistically the possible correlation between thrombocytosis, other clinicopathologic factors and survival parameters. A two-sided p value < 0.05 was considered significant. RESULTS: There were no statistically significant differences between histological subgroups (small cell/SCLC and non-small cell/NSCLC) according to age, disease stage and gender. Sixty-six (25.38%) patients had thrombocytosis before starting treatment. We found no relationship between thrombocytosis and disease stage, gender, age, PS and thrombotic episodes. Thrombocytosis was significantly correlated only with weight loss (p=0.011) and paraneoplastic syndromes (p=0.027). OS was shorter in the thrombocytosis group, but without statistical significance. PFS and DFS did not differ between thrombocytemic and non-thrombocytemic patients. CONCLUSION: Pretreatment thrombocytosis is not an independent prognostic factor of survival in lung cancer patients and is related with paraneoplastic syndromes.

Detection of prostatic carcinoma: the role of TRUS, TRUS guided biopsy, digital rectal examination, PSA and PSA density.

The purpose of this study was to evaluate the efficacy of various diagnostic tests including transrectal ultrasound (TRUS), TRUS guided biopsy, digital rectal examination (DRE), prostate specific antigen (PSA), and prostate specific antigen density (PSAD) in detecting prostatic carcinomas. One hundred and thirty-four men underwent TRUS guided random, or directed and random sonographic biopsies of the prostate. The mean age was 64.67 (range, 31- 88) years. Indications for biopsy were abnormal findings suggesting prostatic carcinoma on DRE or increased levels of PSA, defined as 4.0 ng/ml or greater in a monoclonal antibody assay. PSAD was calculated by dividing the serum PSA in ng/ml to the volume of the entire prostate in cm3. The biopsy results were grouped as benign, malign and, prostatitis. The patients were also divided into three groups according to their PSA values. Of the 134 patients evaluated, 31 (23.1%) had prostate adenocarcinoma, 89 (66.4%) had benign prostatic tissue, hyperplasia or prostatic intraepithelial neoplasia, and 14 (10.4%) had prostatitis. The mean PSA and PSAD of the carcinoma group were significantly higher than those of the noncancer group. In the group of patients with PSA levels between 4 and 10 ng/ml, abnormal TRUS or DRE increased cancer detection rate, where neither PSA nor PSAD was capable of discriminating the patients with and without cancer. PSAD did not prove to be superior to the other diagnostic tests in this study. We recommend biopsy when either TRUS or DRE is abnormal in patients with PSA levels between 4 and 10 ng/ml. In the patients with PSA levels greater than 10 ng/ml, biopsy is indicated whatever the findings on TRUS or DRE are, since cancer detection rate is high.