Perran Fulden Yumuk

Prolonged interval in prophylactic heparin flushing for maintenance of subcutaneous implanted port care in patients with cancer.

The long-term use of subcutaneous implanted ports for chemotherapy in cancer patients has been associated with the occurrence of thrombosis and infection. In this study, we compared the safety and efficacy of administration of 1000 U of heparin flushes in prolonged interval (every 6 weeks) with standard dose and schedule (500 U every 4 weeks) for port-related infections and thrombosis during periods of non-use. Data were collected retrospectively from patients treated for various cancer types (matched as 2:1 for age, gender, stage of the disease). Patients who had diseases that could cause thrombosis or bleeding in their past medical history, or were taking oral anticoagulants, or had contraindications for heparin usage were excluded. After completing their chemotherapy, 59 patients received prolonged interval, while 30 patients received standard schedule. All patients were followed for at least 1 year. No clinically documented port-related infection or thrombosis has been found in both groups. Also, none of the devices was removed during this time. Prophylactic flushing of central venous ports with 1000 U of heparin in every 6 weeks might be a safe, easy, cheaper, comfortable and effective alternative to standard dose and schedule for preventing thrombosis and infections.

Adoption of pleurectomy and decortication for malignant mesothelioma leads to similar survival as extrapleural pneumonectomy

OBJECTIVE We changed our surgical approach to malignant pleural mesothelioma (MPM) in August 2011 and adopted pleurectomy and decortication (PD) instead of extrapleural pneumonectomy (EPP). In this study, we analyzed our perioperative and survival results during the 2 periods. METHODS All patients who underwent surgical intervention for MPM during 2003-2014 were included. Data were retrospectively analyzed from a prospective database. Before August 2011, patients underwent evaluation for EPP and adjuvant chemoradiation (group 1). After August 2011, patients were evaluated for PD and adjuvant chemotherapy and/or radiation (group 2). Demographic characteristics, surgical technique, histology, side, completeness of resection, and types of treatments were recorded. Statistics was performed using Student t test, χ(2) tests, uni- and multivariate regression, and Kaplan-Meier survival analysis. RESULTS The same surgical team operated on 130 patients. Median age was 55.7 years (range, 26-80 years) and 76 were men. EPP and extended PD was performed in 72 patients. Ninety-day mortality was 10%. Median survival was 17.8 months with a 5-year survival rate of 14%. Uni- and multivariate analyses showed that epithelioid histology, stage N0, and trimodality treatment were associated with better survival (P = .039, P = .012, and P < .001, respectively). Demographic variables and overall survival (15.6 vs 19.6 months, respectively) were similar between the groups, whereas nonepithelioid histology, use of preoperative chemotherapy, and incomplete resections were more frequent in group 2 (P < .001, P < .001, and P = .006, respectively). Follow-up was shorter in group 2 (22.5 ± 20.6 vs 16.4 ± 10.9 months; P < .001). CONCLUSIONS Adoption of PD as the main surgical approach is not associated with survival disadvantage in the surgical treatment of MPM.

How do lung cancer specialists follow their patients with stage III non-small cell lung cancer (NSCLC) after definitive treatment? - A short report

Although pretreatment evaluations are well defined for the diagnosis of radically treatable NSCLC, we have very little data about the follow-up of these patients after completion of therapy, especially for stage III patients. No documented standards for surveillance were set in the NCCN, ACCP or ESMO guidelines. In order to determine the standard practice patterns of lung specialists, a survey was done. Physicians were asked which tests they do for pretreatment evaluation and also on asymptomatic patients during their post-treatment follow-up. The survey was sent to 192 centres which were part of the EORTC Lung Cancer Group. Thirty-eight centres from 12 different countries replied. Results showed that almost all the centres are doing very similar pretreatment evaluation procedures in stage III NSCLC. In the post-treatment follow-up setting, results were more varied in terms of frequency and type of scans used. The most commonly used test was a computed tomography (CT) of the chest and abdomen at 3 months post-treatment. Positron emission tomography (PET)/CT and magnetic resonance imaging (MRI) of the brain with contrast were done only in symptomatic patients. This audit suggests that one CT scan at 3 months after the end of radical treatment has become a standard with little evidence showing it is better than a chest radiography (CXR). These data should be used to encourage research into molecular parameters or new imaging techniques that could be tested as more sensitive methods of picking up relapse in radically treated stage IIIA patients who has a high relapse rate in the first 12 months.

Results of paclitaxel (day 1 and 8) and carboplatin given on every three weeks in advanced (stage III-IV) non-small cell lung cancer

BackgroundBoth paclitaxel (P) and carboplatin (C) have significant activity in non-small cell lung cancer (NSCLC). The weekly administration of P is active, dose intense, and has a favorable toxicity profile. We retrospectively reviewed the data of 51 consecutive patients receiving C and day 1 and 8 P chemotherapy (CT) regimen in advanced stage NSCLC to evaluate the efficacy and toxicity.MethodsPatients treated in our institutions having pathologically proven NSCLC, no CNS metastases, adequate organ function and performance status (PS) ECOG 0–2 were given P 112.5 mg/m2 intravenously (IV) over 1 hour on day 1 and 8, followed by C AUC 5 IV over 1 hour, repeated in every three weeks. PC was given for maximum of 6 cycles.ResultsMedian age was 58 (age range 39–77) and 41 patients (80%) were male. PS was 0/1/2 in 29/17/5 patients and stage was IIIA/IIIB/IV in 3/14/34 patients respectively. The median number of cycles administered was 3 (1–6). Seven patients (14%) did not complete the first 3 cycles either due to death, progression, grade 3 hypersensitivity reactions to P or lost to follow up. Best evaluable response was partial response (PR) in 45% and stable disease (SD) in 18%. Twelve patients (24%) received local RT. Thirteen patients (25%) received 2nd line CT at progression. At a median follow-up of 7 months (range, 1–20), 25 (49%) patients died and 35 patients (69%) progressed. Median overall survival (OS) was 11 ± 2 months (95% CI; 6 to 16), 1-year OS ratio was 44%. Median time to progression (TTP) was 6 ± 1 months (95% CI; 4 to 8), 1-year progression free survival (PFS) ratio was 20%. We observed following grade 3 toxicities: asthenia (10%), neuropathy (4%), anorexia (4%), anemia (4%), hypersensitivity to P (2%), nausea/vomiting (2%), diarrhea (2%) and neutropenia (2%). Two patients (4%) died of febrile neutropenia. Doses of CT were reduced or delayed in 12 patients (24%).ConclusionsP on day 1 and 8 and C every three weeks is practical and fairly well tolerated outpatient regimen. This regimen seems to be comparably active to regimens given once in every three weeks.

Clinical Outcome of Turkish Metastatic Breast Cancer Patients with Currently Available Treatment Modalities - Single Center Experience

BACKGROUND Breast cancer is the most common malignancy and the second leading cause of cancer-related death among women in the developed countries. Despite advances in screening, improved local therapies and adjuvant systemic treatments, median survival of metastatic breast cancer patients (MBC) is in the range of 2-3 years at most. We aimed to investigate whether the prognostic factors and therapeutic responses of our Turkish patients are similar to those in the literature. MATERIALS AND METHODS We reviewed the medical records of MBC patients who had been treated in our institution between 1999-2009 and analyzed their clinicopathological features and survival outcomes retrospectively. RESULTS A hundred and sixty patients were included. Median age was 47 (23-82), median follow up was 24 (2-186) months. At the time of diagnosis 59% of patients were under the age of 50 and 46% were postmenopausal. The majority (37%) had multiple sites of metastases. Forty percent received endocrine therapy and 40% chemotherapy as first line metastatic treatment. Thirty (20%) patients were treated with molecular targeting agents like trastuzumab, lapatinib and sunitinib, frequently combined with a chemotherapy agent. Five-year overall survival (OS) was 32% and median OS was 38 months for the whole group. Five year progression free survival (PFS) was 10% and median PFS was 10 months. Menopausal status, hormone receptor expression and disease free status had a significant impact on overall survival in the multivariate analysis (p 0.018, p 0.018 and p:0.003, respectively). CONCLUSIONS All our patients were treated with the modern oncologic therapies recommended by the international guidelines. From our data, MBC patients live up to 3-4 years, indicating that further improvement beyond that requires development of new treatment modalities. The survival outcomes of our patients were consistent with the data reported in the literature.

Concurrent chemoradiotherapy with low dose weekly gemcitabine in stage III non-small cell lung cancer

BackgroundCombined chemoradiotherapy (CRT) is the treatment of choice for stage III NSCLC. Gemcitabine (G) is a novel deoxycitidine analogue that has been proven to be a potent radiosensitizer. Twenty-two consecutive patients were treated with concurrent CRT to demonstrate the tolerability and efficacy of low dose G given weekly as radiosensitizer in stage III NSCLC.MethodsPatients with KPS ≥70, adequate bone marrow reserve, with no prior radiotherapy (RT) and surgery were included. Eighteen patients had received prior induction chemotherapy (CT). G (75 mg/m2/week) was infused over 1 hour for 6 weeks. Thoracic RT was given two hours later over 6 weeks at 1.8 Gy/day fractions (total dose of 61.2 Gy). Pulmonary toxicity was evaluated with computed tomography scans in 6 weeks.ResultsMedian age was 60 years (range, 48–75), median follow-up was 15 months (range, 2–40). Sixty-eight percent of patients were male and median KPS score was 90. Conformal 3D-RT planning was used in 64% of patients. G was given for a median of 5 weeks (range 1–9). Twelve patients (54.6%) received all planned CT. G was stopped because of intolerance in 6 and death in 2 patients. Seven patients (31.8%) had radiation pneumonitis. Twenty patients were evaluated for overall response, 1 patient (4.5%) had clinical CR, 81.8% had PR while 9.5% had SD. Median overall survival (OS) was 14 ± 5 months (95% CI 3–25). One- and 2-year OS rates were 55% and 38%. Sixteen patients died of disease-related events (6 with progression of primary tumor, 8 due to metastatic disease), 2 patients died of other causes. One- and 2-year progression-free survival and local control rates were 56%, 27% and 79%, 51%, respectively.ConclusionG might be used as radiosensitizer for patients with stage III NSCLC who could not receive full doses CT with concurrent RT.

D-dimer--can it be a marker for malignant gastric lesions?

(14 of these had metastasis), 5 (14%) had stage IIIB, 7 (20%) had IIIA, and 2 (6%) had stage II disease. Plasma D-dimer levels were significantly higher in patients with malignant gastric lesions (5.159 /10.46 mcg/ml [range: 0.22 � /40.75 mcg/ml] for adenocarcinoma vs 0.759 /1.09 mcg/ml [range: 0.04 � /4.72 mcg/ml] for benign lesions, p B /0.001). This was also true for patients with stages I to III gastric cancer compared with benign lesions (1.369 /1.16 mcg/ml for stages I to III patients vs 0.759 /1.09 mcg/ml for benign lesions; pB /0.001). The cut-off point of 0.585 mcg/ml was selected as best lower than median D-dimer level for benign lesions. The group with gastric cancer and the group with benign gastric diseases were used to calculate sensitivity and specificity. The sensitivity at a D-dimer level of 0.585 mcg/ml was 86% (95% confidence interval 71% to 95%). The specificity at this value was 81% (95% confidence interval 64% to 93%). The positive and the negative predictive value were both 84%. There were 29 patients with gastric cancer whose levels were 0.585 mcg/ml, while only 6

Macroscopic complete resection is not associated with improved survival in patients with malignant pleural mesothelioma

Objective: Macroscopic complete resection (MCR) is the recommended surgical strategy in malignant pleural mesothelioma. Our objective was to analyze whether MCR influences survival in malignant pleural mesothelioma. Methods: Between 2002 and 2016, 154 patients underwent pleurectomy decortication (n = 90), extrapleural pneumonectomy (n = 42), or exploratory/diagnostic procedures (n = 22) in a single institution. Patient data were recorded in a prospective database. Patients who underwent surgical resection (n = 132) were analyzed according to MCR as a whole group and after propensity score matching based on gender, age, histology, clinical T and N status, adjuvant chemotherapy, and trimodality treatment. Kaplan‐Meier survival and univariate and multivariate analyses were performed. Results: Median age was 56 years (range, 26 to 80 years) and 62 were women. One hundred ten had epithelioid histology. MCR was achieved in 75 patients (49%). In‐hospital mortality was seen in 7 patients (4.5%). Preoperative chemotherapy was applied in 32 patients. One hundred thirty‐three patients underwent adjuvant treatment (45 had chemoradiation). Mean follow‐up was 21 ± 19 months. Overall median survival, 2‐year, and 5‐year survivals were 18.1 months, 36%, and 16%, respectively. There was no difference in median survival between patients who underwent MCR (21.4 months) and who did not (16.3 months) (P = .6). Following propensity score matching (23 patients in each group), median survivals were similar (13.3 vs 14.2 months; P = .63). Conclusions: MCR was not associated with improved survival in malignant pleural mesothelioma. We need to clearly define MCR and identify subgroups of patients who would benefit from this principle because minimal versus extensive and location of gross residual disease may have different influences on survival.

Another adverse effect of vemurafenib: Gingival hyperplasia.

Dear Editor, Vemurafenib is a small-molecule inhibitor approved in the treatment of BRAF V600 mutation-positive metastatic melanoma. This targeted drug has notoriously been associated with a unique spectrum of skin toxicities which has been reported to be seen in all treated patients in a prospective study. Among these are maculopapular rash, photosensitivity, plantar hyperkeratosis, hand–foot reaction, keratosis pilaris-like reaction, verrucous papillomas and malignancies, notably keratoacanthoma/squamous cell carcinoma. To the best of our knowledge, gingival hyperplasia related to vemurafenib has only once been reported in a patient with metastatic melanoma showing progression despite vemurafenib treatment. Here, we report a similar observation, further underscoring gingival hyperplasia as a possible adverse effect of vemurafenib. A 33-year-old man with metastatic melanoma showing BRAF V600 mutation was referred to our clinic. He had stable disease under vemurafenib treatment for 6 months. During the course of vemurafenib treatment, mild alopecia, plantar hyperkeratosis and keratosis pilaris-like folliculocentric eruption were noted. In addition, he complained of new-onset painful swelling of the gums for 1 month. Oral examination revealed slightly frambesiform gingival hyperplasia accompanied by superficial erosions, more pronounced on the marginal and attached parts of the maxillary gingiva (Fig. 1). Due to decreased oral intake, vemurafenib treatment was interrupted for 1 week, leading to modest amelioration of the oral symptoms. Based on the absence of concomitant medications and medical conditions known to be associated with gingival hyperplasia and temporal relationship, gingival hyperplasia was attributed to vemurafenib. At the final examination, a combination treatment of vemurafenib and cobimetinib was planned. The cutaneous side-effects of vemurafenib have tentatively been explained by the paradoxical activation of retrovirusassociated sequence (RAS), which is an upstream component of the RAS–RAF–mitogen-activated protein kinase kinase– extracellular signal-regulated kinase intracellular signaling pathway, and thus, have been designated as “RASopathic”. Supporting this theory, many cutaneous adverse effects of vemurafenib, such as keratosis pilaris and plantar hyperkeratosis, coincide with the spectrum of cutaneous findings seen within the context of the inherited “RASopathies”. Mangold and colleagues argued that gingival hyperplasia may be another RASopathic adverse effect of vemurafenib. We hypothesize that another molecular pathomechanism may possibly account for the vemurafenib-associated gingival changes. Secondary resistance to vemurafenib, which is known to develop in almost all patients after a median interval of approximately 6 months, may involve the activation of an extrinsic pathway, called PI3K–AKT–mammalian target of rapamycin (mTOR). Interestingly, gingival hyperplasia is an important manifestation of both tuberous sclerosis complex and Cowden syndrome,

Cisplatin plus docetaxel combination in the first-line treatment of metastatic non-small cell lung cancer.

AIMS To evaluate activity and toxicity of cisplatin plus docetaxel combination in the first-line treatment of chemotherapy-naive patients with metastatic non-small cell lung cancer. PATIENTS AND METHODS Between October 2004 and July 2008, 186 patients with metastatic non-small cell lung cancer treated with first-line cisplatin plus docetaxel were retrospectively evaluated in 7 centers. The chemotherapy schedule consisted of cisplatin, 75 mg/m(2) iv infusion, and docetaxel, 75 mg/m(2) iv infusion on day 1, every 3 weeks. RESULTS Median age was 56 years (range, 28-75). Eighteen patients (9.7%) were females and 168 (90.3%) were males, with a median ECOG performance status of 1 (range, 0-2). A total of 833 cycles of chemotherapy was administered (median, 4 cycles; range, 1-6). Two patients (1.1%) achieved clinical complete response, 77 patients (41.4%) partial response, and 66 patients (35.5%) stable disease. Median time to disease progression was 6 months (95% CI, 5.54-6.46). Median overall survival was 14.6 months (95% CI, 11.47-17.73). One- and 2-year overall survival was 55.2% and 19.7%, respectively. The most common grade 3-4 hematological toxicities were neutropenia (n = 32, 17.2%) and anemia (n = 4, 2.2%). CONCLUSIONS The cisplatin plus docetaxel combination was effective and safe in the first-line treatment of patients with metastatic non-small cell lung cancer.