Zafer Arik

Can all beta blockers improve the breast cancer survival

Total 88 456 Estrogen receptor Positive 40 (83.3) 309 (73.2) 0.23 Negative 8 (16.7) 113 (26.8) Progesterone receptor Positive 39 (81.3) 306 (72.3) 0.22 Negative 9 (18.7) 117 (27.7) HER2 Positive 12 (22.2) 93 (21.5) 0.38 Negative 32 (77.8) 338 (78.5) Triple negative Yes 4 (9.5) 48 (11.4) 0.40 No 38 (90.5) 372 (88.6) Lenfovascular invasion No 65 (77.3) 292 (71.1) 0.19 Yes 19 (22.7) 119 (28.9) Grade I 14 (18.9) 45 (10.9) 0.08 II 38 (51.4) 186 (45.1) III 22 (29.7) 181 (43.9) T-Stage T1 26 (31.7) 115 (26.6) 0.40 T2 41 (50.0) 235 (54.4) T3 10 (12.2) 60 (13.9) T4 5 (6.1) 22 (5.1) Lymph node status Node ( ) 41 (50) 192 (44.5) 0.13 Node (þ) 41(50) 232 (55.5) Distant metastasis No 74 (85.1) 417 (91.5) 0.07 Yes 13 (14.9) 39 (8.5)

Evaluation of the effect of comorbidity on survival in pancreatic cancer by using “Charlson Comorbidity Index” and “Cumulative Illness Rating Scale”

SummaryBackgroundEffect of comorbidity on the treatments that patients receive is not clear, as healthy elderly patients and the elderly with less comorbid diseases are included in the studies. In the present study, the effect of comorbidity on the survival was evaluated using Charlson Comorbidity Index (CCI) and Cumulative Illness Rating Scale (CIRS).Material and methodThe general features and comorbid diseases of the pancreatic cancer patients were retrospectively screened from the patient files using the automated system. CCI and CIRS were used as the comorbidity indices.ResultsA total of 106 patients with pancreatic cancer were included in the study. The median overall survival rate was 9.0 [95 % confidence interval (CI): 6.7–11.3] months. The median overall survival rate was found as 9.4 (95 % CI: 6.7–12.1) months in the patients whose CCI score was ≤ 2 and was found as 6.2 (95 % CI: 4.0–8.3) months in the patients with CCI scores ≥ 3 (p = 0.05). The median overall survival rate was calculated as 9.8 (95 % CI: 6.3–13.4) months in the patients with CIRS scores ≤ 2 and was calculated as 8.3 (95 % CI: 6.0–10.6) months in the patients with CIRS scores ≥ 3 (p = 0.51). When surgery, radiotherapy, grading, and CCI score were evaluated using multivariate analysis, it was observed that only the treatment modality had a significant effect on the survival rate.ConclusionThe results on the use of comorbidity indices are contradictory for the cancers with lower survival rates such as pancreatic cancer. New prognostic scales might be developed for this patient group by considering the side effects of chemotherapy.ZusammenfassungGrundlagenDie Auswirkung von Begleiterkrankungen auf den Erfolg der Therapien, die Patienten erhalten, ist ungesichert, da oft gesunde ältere Patienten beziehungsweise Ältere mit nur wenigen Begleiterkrankungen in die Studien eingeschlossen werden. In der vorliegenden Studie wurde der Einfluss von Begleiterkrankungen auf das Überleben durch Verwendung des Charlson Komorbiditäts Index (CKI) und der Kumulativen Erkrankungs-Bewertung Skala (KEBS) bewertet.Material und MethodenDie Allgemeinsituation und Begleiterkrankungen von Patienten mit Pankreaskrebs wurden retrospektiv an Hand der Krankengeschichten mit Hilfe eines automatisierten Systems erhoben. CKI und KEBS wurden als Indices verwendet.ErgebnisseInsgesamt wurden 106 Patienten mit Pankreaskrebs in die Studie aufgenommen. Die mediane Gesamt-Überlebenszeit betrug 9 Monate (95 % CI; 6,7–11,3). Bei den Patienten mit einen CKI < 2 lag die Gesamtüberlebenszeit bei 9,4 Monaten (95 % CI; 6,7–12,1); bei den Patienten mit einem CKI ≥ 3 lag sie bei 6,2 Monaten (95 % CI; 4,0–8,3). Bei der Einteilung nach KEBS ergab sich eine Gesamtüberlebenszeit von 9,8 Monaten (6,3–13,4) bei jenen ≤ 2 und von 8,3 (95 % CI: 6,0–10,6) bei einem KEBS Wert von ≥ 3 (p = 0,51). Die Berücksichtigung der Operation, der Bestrahlung, des Stadiums und des CKI Scores in der Multivarianz Analyse ergab, dass nur die Therapiemodalität einen signifikanten Einfluss auf die Überlebensrate hatte.SchlussfolgerungDie Ergebnisse des Einsatzes von Komorbiditätsindices sind bei Krebserkrankungen mit geringer Lebenserwartung, wie dem Pankreaskrebs, widersprüchlich. Neue prognostische Skalen sollten für diese Patienten unter Berücksichtigung der Nebenwirkungen der Chemotherapie erstellt werden.

Dermatomyositis complicated with a soft tissue sarcoma

To the Editor, The association between malignancy and dermatomyositis (DM) was known for nearly a century, but its significance remained unclear. The incidence of the malignancy increased five- to sevenfold compared to general population [1]. The peak incidence of malignancy diagnosis occurs within the 2 years of the diagnosis of dermatomyositis. The most common cancers associated with dermatomyositis include ovarian, lung, pancreatic, breast, and stomach cancer [2]. We present here a case of dermatomyositis and soft tissue sarcoma at the same time at diagnosis. In our review of the literature, coincidence of dermatomyositis and soft tissue sarcoma was not reported before.

Small cell carcinoma of the urinary bladder with hypercalcemia.

To the editor, Small cell carcinomas are usually seen in the lung and represents approximately 16% of lung cancers [1]. Small cell carcinoma of the urinary bladder is a rare tumor accounting for less than 1% of all bladder tumors and represents 0.1–0.4% of all small cell carcinomas [2]. Small cell carcinomas in the bladder usually have an aggressive clinical course, often presenting with metastases at the time of diagnosis. Although most clinicians believe that optimal treatment for small cell carcinoma of the bladder is a combination of surgical resection and adjuvant chemotherapy, the surgical resection is not curative, with adjuvant chemotherapy extending patient survival. This letter presents a case of small cell carcinoma of the bladder with hypercalcemia, which is rarely seen. A 52-year-old woman presented with acute painless hematuria and backache. Physical examination revealed a very ill patient with common pain and distended urinary bladder. The patient had been a smoker for 33 years. Laboratory evaluation showed a mild anemia with microscopic hematuria. Abdominal tomography revealed a 50 9 36 mm hypoechoic mass in the left lateral side of urinary bladder. The patient was operated and radical cystectomy with pelvic lymphadenectomy was performed. The pathology revealed poor differentiation small cell carcinoma with lymph node metastases. Whole body–bone scintigraphy was normal, and no distant metastasis was observed. The patient was treated with cisplatin–etoposidbased chemotherapy. After three cycles of chemotherapy, patient readmitted with skeletal pain and hypercalcemia. Laboratory results showed calcium level as high as 14.4 mg/dl (normal range 8.6–10.2 mg/dl) with normal parathyroid hormone level and renal functions. Further works up including bone scan showed that bilateral femoral head uptake compatible with metastases. By zoledronic acid treatment, the patient’s serum calcium level was controlled. The local radiotherapy was given to the bilateral head of femur. And in the second step, cyclophosphamid–adriamisin–vincristin (CAVi) chemotherapy was given. Then, the patient was still treated with CAVi protocol and zoledronic acid monthly for 4 months. Hypercalcemia associated with certain types of malignancy is a well-known finding. Hypercalcemia has been reported to occur in up to 20–30 percent of patients with cancer at some time during the course of their disease [3]. The detection of hypercalcemia in a patient with cancer signifies a very poor prognosis; approximately 50 percent of such patients die within 30 days [4]. Small cell carcinoma rarely presented with hypercalcemia. Hypercalcemia associated with cancer results by prostaglandin, osteoclast stimulating factor, parathormone-like substance, or pseudohyperparathyroidism [5]. Genitourinary small cell carcinoma has a poor prognosis, and radical surgeries with cisplatin-based chemotherapy are the only factors improved survival [6]. The first case of small cell carcinoma of urinary bladder reported in 1981, the only small cell carcinoma of urinary bladder with hypercalcemia reported in 1985 by Reyes et.al [7]. Small cell carcinoma associated with hypercalcemia is a rare finding. In our case, there was no relation between serum parathyroid hormone level and hypercalcemia. Hypercalcemia in our patient is probably related to bone invasion M. A. N. Şendur (&) S. Aksoy Z. Arık Ş. Yaman N. Y. Özdemir D. Uncu N. Zengin Department of Medical Oncology, Ankara Numune Education and Research Hospital, 06100 Sihhiye, Ankara, Turkey e-mail: masendur@yahoo.com.tr

Plasma VEGF levels may not accurately reflect the truth all the time

To the editor, We read with great interest the study by She-Juan An et al., which showed that posttreatment plasma VEGF levels associated with the overall survival of patients with advanced non-small-cell lung cancer treated with bevacizumab plus chemotherapy. In this study, before and 6 weeks after treatment, vascular endothelial growth factor (VEGF) levels measured. Also, this study showed that low posttreatment VEGF levels associated with better overall survival (OS) [1]. We have some insights for this decrease in serum VEGF levels. VEGF circulating in the blood of patients with cancer may be derived from various sources, as depicted in Fig. 1. Circulating levels of VEGF are dependent on the amount released from tumor cells (Fig. 1A) and/or platelets activated at the tumor-vessel endothelium. Activated platelets release VEGF (Fig. 1B), and platelet consumption causes increased levels of thrombopoietin, which in turn stimulates megakaryopoiesis and platelet production in the bone marrow. Newly produced platelets are larger in size than those produced during steady-state thrombopoiesis, and therefore contain an elevated amount of VEGF (Fig. 1C). Finally, host immune cells as macrophages that infiltrate tumor tissues can be an additional source of VEGF (Fig. 1 D) [2]. Serum VEGF levels have also been found to correlate with platelet count in a mixed population of metastatic cancers and renal cancer, and some investigators have also stated that VEGF should be corrected for platelet counts. To correct for variation in platelet counts between patients, it has been proposed that the concentration of VEGF per platelet (pg/10) can be calculated by dividing the serum VEGF concentration (pg/ml) by the platelet count (910/ml) [3]. In the study, She-Juan An et al., mean VEGF levels decreased from 81.5 pg/ml to 50.5 pg/ml after 6 weeks of treatment (P = 0.08), with a mean reduction of 31 pg/ml in overall. The relationship of the plasma VEGF levels with OS and progression-free survival (PFS), the patients were divided in the two groups based on their median VEGF value. The OS differed significantly between the low and high posttreatment VEGF levels (25.6 months vs. 13.4 months, P = 0.0284). No other relationship was found with plasma VEGF levels. It is known that most cytotoxic chemotherapeutics decrease the platelet count. In this study, thrombocytopenia was developed in 27.3% patients treated with bevacizumab plus chemotherapy. The association between VEGF levels and thrombocytopenia was not reported. Also, it is possible that platelet counts decreased with chemotherapy, but remained within normal limits. Because platelet counts before and after therapy has not been reported, the possible contribution of platelets on the decreasing VEGF levels remains obscure. We believe that the decrease in serum VEGF levels may at least in part be due to decreased platelet counts secondary to chemotherapy, and plasma VEGF levels may not accurately reflect the truth all the time before correcting the VEGF levels for platelet counts. M. A. N. Şendur S. Aksoy (&) Ş. Yaman Z. Arik N. Y. Ozdemir N. Zengin Department of Medical Oncology, Ankara Numune Education and Research Hospital, 06100 Sihhiye, Ankara, Turkey e-mail: saksoy07@yahoo.com

Isolated Testicular Metastasis of Gastric Cancer

Secondary neoplasms of the testis are uncommon and less than 2% of all testicular cancers. Other than leukemia and lymphomas, the most common sites from which metastases occur are the lung and prostate gland. However, here, we report gastric cancer metastasis to the testis, an extremely rare site for gastric adenocarcinomas. We also review the cases of testicular metastasis arising from stomach cancer.

Long-term survivors among breast cancer patients with brain metastases

We read the article by Niwinska et al. [1] in which they carried out a comprehensive analysis of 222 consecutive patients with breast cancer and brain metastases. They found that median survival from brain metastases in recursive partitioning analysis Radiation Therapy Oncology Group prognostic class I, II and III were 15, 11 and 3 months, respectively. A recent retrospective study evaluated clinical data from 420 patients who had been diagnosed with breast cancer and brain metastasis from 1994 to 2004 at M. D. Anderson Cancer Center. In this study, median follow-up after brain metastasis was 6 months (range 0.7–95.9 months) and the overall median survival was 6.8 months [2]. Although the survival outlook for patients with breast cancer metastatic to brain is generally poor, there were some long-term survivors. Eighty-two patients in this study (19.5%) were alive at least 18 months after diagnosis of brain metastasis. Of these 82 patients, 25 patients (30%) were human epidermal growth factor receptor 2 positive. Furthermore, 18 (4.2%) were alive at least 60 months after this diagnosis. Compared with an unselected series of breast cancer patients, this longer surviving population was younger and was predominantly premenopausal. Most of these patients had tumors of ductal histologic type, T stage 1 or 2, N stage 0 or 1 and M0 stage at diagnosis. About half of these patients had estrogen receptor-positive or progesterone receptorpositive disease and 73% had grade III disease. Any or all of these characteristics may explain their potential for prolonged survival. In conclusion, detailed molecular characterization of brain metastases from breast cancer may lead to a more in-depth understanding of the biologic abnormalities that drive this malignant behavior and also may lead to the discovery of new therapeutic targets with improved therapeutic indices.

Effectiveness of low-dose oral etoposide treatment in patients with recurrent and platinum-resistant epithelial ovarian cancer

Abstract The aim of this study was to evaluate the efficacy and toxicity profile of oral etoposide (50 mg/day, days 1–14, every 3 weeks) in recurrent platinum-resistant epithelial ovarian cancer (EOC). 52 recurrent platinum-resistant EOC patients followed up in four centres between April 2000 and December 2013 were analysed retrospectively. There was response in a total of 21 patients [partial response (PR) and stable disease (SD)], 12 of them used etoposide in second and third, and 9 of them used it in fourth- to fifth-lines of treatment. The overall response rate was 19.2% and clinical benefit rate was 40.4% [PR (19.2%), SD (21.2%)]. Median overall survival (OS) and progression-free survival (PFS) was 9.95 months (95%CI, 0.2–19.7 months) and 3.2 months (95%CI 2.6–3.8 months), respectively. Grade III–IV haematologic and non-haematologic adverse events were observed in 7 (13.4%) patients. We consider that oral etoposide (50 mg/day, days 1–14, every 3 weeks) is an effective treatment with a manageable adverse effect profile in recurrent platinum-resistant EOC patients. Impact statement What is already known on this subject: Oral etoposide is an effective option for recurrent EOC patients at a dose of 50–100 mg/m2/day (1–21 days, every 28 days) regimen. However, it has a high toxicity rate. What the results of this study add: Oral etoposide at a dose of 50 mg/kg (1–14 days, every 21 days) is an effective treatment with a manageable toxicity profile in platinum- resistant ovarian cancer patients when it is used as ≤4th-line palliative setting. What the implications are of these findings for clinical practice and/or further research: We need trials evaluating the effect of low-dose oral etoposide combination with bevacizumab or other chemotherapy agents (irinotecan and gemcitabine) in platinum-resistant EOC patients.

Hodgkin Lenfomalı Olguda Santral Sinir Sistemi Tutulumu

Hodgkin lenfomada (HL) Santral Sinir Sistemi (MSS) tutulumu son derece nadirdir. HL’de MSS tutulumu sadece %0,02-0,5 bildirilirken, Non-Hodgkin lenfomada (NHL) MSS tutulumu vakalarin %5-30’unda bildirildi. Norolojik semptomlara ragmen, radyolojik calismalar bu hastalarda her zaman MSS tutulumu tespit etmez. Beyin omurilik sivisi incelemesi atipik Hodgkin lenfoma hucrelerini gosterir. Bu calismada guncel literatur isiginda HL’de MSS tutulumu tartisilacaktir.

Temporal changes in the survival of metastatic renal cell cancer patients and the impact of targeted agents: Single center experience.

519 Background: Though targeted agents have dramatically changed the outcome of metastatic renal cell cancer (mRCC) patients, it has not been possible to show any survival advantage, probably due to substantial cross-over in randomized trials. The change in survival times following the introduction of targeted agents may yield indirect evidence of an improvement in overall survival (OS). Methods: First targeted agents were available in Turkey in 2007. Data from the hospital charts of adult mRCC patients treated between January 2003 and December 2012 were included. Demographic and clinical findings along with patient, tumor, and treatment-related prognostic factors and their correlation with progression-free survival (PFS), and OS were analyzed. Results: One hundred and seventy six patients had metastatic disease. Of these, 107 patients received at least one dose of interferon-α and 74 patients received at least one targeted therapy. Median follow-up was 19.1 months (range 1-97 months) and median OS was 24...