Alev Turker

Platelet size has diagnostic predictive value for bone marrow metastasis in patients with solid tumors

Though not very common, solid tumor involvement of the bone marrow (BM) may have serious consequences. Recent studies have shown that mean platelet volume (MPV) is a good indicator for BM disease in the differential diagnosis of thrombocytopenia. We investigated the significance of MPV in the diagnosis of BM metastasis in patients with solid tumors. Patients with histologically‐verified solid tumors for whom BM biopsy specimens were available (n = 121) and healthy controls (n = 62) were included in this retrospective study. A total of 183 individuals were analyzed. Of the patients, 61 had a diagnosis of BM metastasis (Group A), 60 did not have BM metastasis (Group B). Group B and C (healthy controls) constituted the control group without BM metastasis (n = 122). The mean MPV was 7.0 ± 0.8 fl in patients with BM metastasis and 8.4 fl in the control group (P < 0.001). A cut‐off point of <7.4 fl was found to have significant predictive value according to receiver‐operating characteristics curve analysis. This cut‐off point had 85% positive predictive value and 90% negative predictive value in the diagnosis of BM metastasis (odds ratio: 53; 95% confidence interval: 20–135), and a sensitivity of 82.7% and specificity of 89.6%. MPV can be used as a reliable marker to guide the clinician as to the likely presence or absence of BM metastasis in patients with solid tumors.

Epithelioid sarcoma of vulva: a case report and review of the literature.

Epithelioid sarcoma of vulva is an extremely rare and aggressive tumor. In most patients it is asymptomatic, and the lesions are usually mistaken for benign processes, leading to diagnosis at later stages. We report a case of vulvar epithelioid sarcoma in a 51-yr-old woman presenting with a nodularity of vulva. Left hemivulvectomy with bilateral inguinal lymph node dissection was performed. There was no evidence of distant metastasis at the time of diagnosis. Following adjuvant chemoradiotherapy and three cycles of chemotherapy, the patient developed lung metastasis 4 mo after surgery and died of disseminated disease after 6 mo of diagnosis. Vulvar epithelioid sarcoma is rare; showing different behavior changing from an extremely aggressive tumor to behaviors like low-grade tumors. It is best treated by early diagnosis and initial eradication. Definitive surgery provides excellent local control and survival in low-grade tumors. The role of adjuvant treatment remains to be determined.

Craniospinal radiotherapy in adult medulloblastoma.

Purpose:To evaluate the outcome and prognostic factors of adult patients with medulloblastoma.Patients and Methods:26 adult medulloblastoma patients with a median age of 27 were subjected to craniospinal radiotherapy. A dose of 30.6 Gy with 1.8 Gy/fraction/day was prescribed to M0 patients, while 36 Gy were to be applied in patients with positive cerebrospinal liquor findings. The posterior fossa was boosted to 54 Gy. While 20 patients underwent external-beam radiotheray alone, only six received sequential adjuvant chemotherapy.Results:Male/female ratio was 1.2. Preradiotherapy Karnofsky performance status was recorded as median 100%. 50% were classified as poor risk (n = 10, subtotal resection; n = 3, M+). The median follow-up time was 46.5 months. The 5-year actuarial survival rates for recurrence-free, distant metastasis-free, disease-free, and overall survival were 82.5%, 90.8%, 73.5%, and 89.7%, respectively. Patient characteristics, treatment factors and tumor characteristics failed to show any significance in univariate analysis. Grade 3 or 4 late morbidities were not observed.Conclusion:Yet, the current standard of care seems to remain craniospinal irradiation after maximal surgical resection of the primary neoplasm without clear indications for adjuvant chemotherapy.Ziel:Evaluation der Ergebnisse und Prognosefaktoren bei erwachsenen Patienten mit Medulloblastom.Patienten und Methodik:Insgesamt 26 erwachsene Patienten mit Medulloblastom (medianes Alter 27 Jahre) wurden kraniospinal bestrahlt. Dabei erhielten M0-Patienten eine Gesamtdosis von 30,6 Gy in Einzelfraktionen von 1,8 Gy/Tag, und bei Patienten mit einem positiven Liquorbefund wurden insgesamt 36 Gy appliziert. Die hintere Schädelgrube wurde bis zu einer Gesamtdosis von 54 Gy geboostet. 20 Patienten erhielten eine alleinige postoperative Bestrahlung, sechs Patienten eine sequentielle adjuvante Chemotherapie.Ergebnisse:Das Verhältnis von Männern zu Frauen lag bei 1,2. Der vor der Strahlentherapie bestehende mediane Karnofsky-Index betrug 100%. 50% der Patienten wurden als Hochrisikopatienten eingestuft (subtotale Resektion: n = 10, M+: n = 3). Die mediane Nachbeobachtungszeit betrug 46,5 Monate. Die Überlebensraten nach 5 Jahren für das rezidivfreie Überleben, das metastasenfreie Überleben, das krankheitsfreie Überleben und das Gesamtüberleben lagen bei 82,5%, 90,8%, 73,5% und 89,7%. Es fanden sich keine signifikanten Prognosefaktoren in der univariaten Analyse. Spättoxizitäten des Grades 3 oder 4 wurden ebenfalls nicht beobachtet.Schlussfolgerung:Die Standardbehandlung von Patienten mit einem Medulloblastom im Erwachsenenalter bleibt die kraniospinale Bestrahlung nach maximaler chirurgischer Resektion, ohne klare Indikation für eine adjuvante Chemotherapie.

High dose sequential chemotherapy and autologous stem cell transplantation in patients with relapsed/refractory lymphoma

Although high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has become the standard approach for patients with relapsed/refractory Hodgkins disease (HD) or non-Hodgkins lymphoma (NHL), more than 50% of patients will experience relapse following ASCT. High-dose sequential chemotherapy (HDSC) can intensify the conventional salvage treatment and improve the outcome of ASCT by maximal debulking of the tumor load with the use of non-cross resistant drugs, each at their maximal tolerated doses. We conducted a phase II study in 40 patients with relapsed/refractory HD (n = 18) and NHL (n = 22) using HDSC followed by ASCT. Only patients sensitive to salvage chemotherapy were eligible for the protocol, consisting of three phases. Phase I consisted of cyclophosphamide (4.5 g/m2) followed by G-CSF and peripheral blood stem cell (PBSC) collection. Phase II consisted of etoposide (2 g/m2). The transplant phase consisted of mitoxantrone (60 mg/m2) and melphalan (180 mg/m2) followed by PBSC infusion. Eleven out of nineteen patients with B-cell lymphoma received rituximab. Prior to HDSC, 45% of the patients were in complete remission (CR) and 55% were in partial remission (PR). After completion of all phases of the protocol, 35 out of 39 evaluable patients achieved CR (90%) and this was durable in 30 (75%) patients with a projected progression-free survival (PFS) rate at 4 years of 71.7%. Treatment-related mortality rate at day +100 was 2.5% (n = 1). At a median follow-up of 32 months (range, 3 – 61), nine patients relapsed/progressed and eleven patients died. The estimated 4-year PFS and overall survival (OS) were 72.2% and 47.6% in HD patients and 70.3% and 69.4% in NHL patients, respectively. Factors predicting OS were response to conventional salvage therapy and stage prior to salvage therapy. When compared to patients achieving PR, patients who attained CR prior to HDSC had a significantly higher probability of 4-year OS (78.4% vs 31.3%, p = 0.02). Three prognostic subgroups were defined according to the score determined by stage prior to initiation of salvage chemotherapy, remission duration prior to salvage (refractory/early relapse vs. late relapse) and response to salvage. Prognostic score was found to predict OS, PFS and event free survival (EFS). In conclusion, HDSC followed by ASCT is an effective salvage therapy with acceptable toxicity, allowing further consolidation of response attained by conventional salvage therapy.

Modified ESHAP as Salvage Chemotherapy for Recurrent or Refractory Non-Hodgkin’s Lymphoma: Results of a Single-Center Study of 32 Patients

Background: We have evaluated the clinical efficacy and toxicity of a modified etoposide, methylprednisolone, cytarabine and cisplatin (ESHAP) chemotherapy regimen that has been used by the Hacettepe University Department of Medical Oncology (Ankara, Turkey) since 1993. Methods: Thirty-two patients (18 men and 14 women) with refractory or recurrent non-Hodgkin’s lymphoma (NHL) were treated with this protocol. The median age of the patients was 39 years (range 21–66 years). Patients were hospitalized during therapy. On the first day, 2 g/m2 cytarabine was given, followed on days 2–5 by 60 mg/m2 etoposide, 500 mg of methylprednisolone and 25 mg/m2 cisplatin. After two cycles of chemotherapy, clinical efficacy was assessed by clinical examination, chest radiography, ultrasonography and/or computed tomography. The complications were assessed on the basis of the World Health Organization criteria. Results: Nine patients (28%) had a complete response and 8 patients (25%) had a partial response. In responders, the median duration of remission was 6 months. By the end of the first year, 27% of the patients were still disease free and 66% were alive. High serum levels of lactate dehydrogenase had an adverse effect on disease-free survival, but no effect on overall survival (OS). The only unfavorable prognostic factor for OS was the presence of bulky disease. Neutropenia developed in 59% of patients, and febrile neutropenia developed in 74% of these patients, requiring hospitalization for an average of 8 days. Three patients died of neutropenia-associated sepsis despite broad-spectrum antibacterial and antifungal treatment. Thrombocytopenia was detected in 10 patients and anemia in 3 patients; among these, 7 patients with thrombocytopenia and 1 patient with anemia required transfusions. Conclusions: The modified ESHAP regimen induced remission in more than half of the patients with refractory or recurrent NHL. However, the duration of remission was brief. Moreover, significant myelotoxicity was common, and the risk of treatment-related death was 9%.

Maintenance therapy with alpha-interferon following first-line VAD in multiple myeloma

Abstract: The aim of this study was to evaluate the response characteristics of vincristine, adriamycin and dexamethasone (VAD) as a first‐line chemotherapy and to determine the efficacy of maintenance alpha‐interferon (α‐IFN) in multiple myeloma (MM). Between January 1985 and December 1994, a prospective trial was performed in stage II and III MM patients. The study population received only VAD with no maintenance therapy before 1990 (n = 31), and those recruited after 1990 (n = 33) were planned to be maintained with α‐IFN (5 mU, 3 times per wk) during the plateau to a maximum of 2 yr. Median follow‐up duration (44 vs. 39 months), time to response (3.4 vs. 3.5 months) and rate of objective response (61.3%, 19/31 and 63.6%, 21/33) were similar in VAD‐only and VAD+IFN groups, respectively. The survival analyses revealed higher median progression‐free (39.6 vs. 12 months) and overall survival (65+ vs. 24 months) durations in VAD+IFN group compared to VAD‐only group. VAD regimen was well tolerated and IFN‐related side effects were reversible. These findings denote that IFN maintenance prolongs the duration of response obtained by VAD.

Thymic epithelial neoplasia: a study of 58 cases.

Primary thymic epithelial neoplasms (PTENs) are uncommon tumors of anterior mediastinum with a broad range of biological characteristics. We retrospectively reviewed 58 consecutive patients with a diagnosis of PTENs that were confirmed pathologically during 28 yr. There were 58 patients, 31 males (53.4%) and 27 females (46.6%), with a mean age of 43.6 ±13.8 yr (range, 17–73 yr). Twenty-one (36.2%) patients presented at the Masaoka stage I, 13 (22.4%) patient at stage II, 18 (31.0%) patient at stage III, and 6 (10.4%) patients at stage IV. Forty-five (77.7%) patients had myasthenia gravis, 1 (1.7%) immune deficiency, 1 (1.7%) pancytopenia, and 1 (1.7%) nephrotic syndrome. No paraneoplastic syndrome was associated in 10 (17.2%) patients. Complete resection was accomplished in 41 (70.7%) patients, while incomplete resection was performed in 8 (13.8%) patients. In nine (15.5%) patients only biopsy was carried out. Radiotherapy was administered to 19 (32.8%) patients. Eleven (19.0%) out of 58 who presented at advanced stages (at least III) received chemotherapy. Median follow-up period was 59 mo (range, 1-278 mo). During the follow-up period, 17 deaths occurred. Five patients (29.4%) died of tumor-related causes, and the remaining 12 patients died of other causes (cardiovascular diseases [n = 1, 5.9%], sepsis [n = 4, 23.5%], and MG-related respiratory insufficiency [n = 7, 41.2%]). The overall survival rates at 5 yr and 10 yr were 63.9% and 54.2%, respectively. Tumor-related survival rates at 5 yr and 10 yr were 89.0% and 83.2%, respectively. In our series, disease stage, presence or absence of myasthenia gravis, and tumor size did not affect survival (p> 0.05), either. Complete resection of the tumor seems to be the best predictive factor for long-term survival.

Concomitant Mycobacterium tuberculosis and Aspergillus niger infection in a patient with acute myeloid leukemia

Primary cutaneous infection by Aspergillus spp. is an uncommon form of aspergillosis in patients with severe immunosuppression, e.g. patients with HIV infection or hematological malignancies. Disruption of the dermal integrity by trauma or maceration, followed by colonization of the wound by Aspergillus spp. creates a suitable environment for cutaneous infection. Despite aggressive therapy with amphotericin, primary cutaneous aspergillosis can lead to disseminated disease with fatal consequences. Tuberculosis is another rare infection in patients with hematological malignancies, but when present it is usually disseminated. We present a 46-year-old woman with acute myeloid leukemia who developed concomitantly Mycobacterium tuberculosis and Aspergillus niger infection. Cutaneous aspergillosis was diagnosed during neutropenia after induction therapy, which later became disseminated disease during antifungal therapy. Tuberculosis infection was diagnosed in a scalene lymph node biopsy specimen. The patient achieved remission of her underlying disease and responded very well to antituberculous and antifungal therapy.

Embryonal rhabdomyosarcoma of the larynx.

m t ore than 95% of laryngeal tumors in adults are squamous cell carcinoma. Laryngeal involvement by rhabomyosarcoma in adults is extremely rare. A 28-year-old male atient with the complaint of hoarseness presented with a aryngeal mass. Biopsy revealed embryonal rhabdomyosaroma. Combination chemotherapy was initiated consisting of yclophosphamide, doxorubicin, cisplatin, and vincristine. Folowing induction chemotherapy, clinical and radiological comlete response was obtained. Radiotherapy was applied after nduction chemotherapy. Squamous cell carcinoma is the most ommon histology among the laryngeal malignancies, making p more than 95% of laryngeal tumors. Mesenchymal tumors onstitute less than 1% of the cases, primarily in children. Of hem, rhabdomyosarcoma is the least common and the larynx s a primary localization is extremely unusual. In children, the ost common variety of laryngeal rhabdomyosarcoma is the mbryonal type, whereas in adults, pleomorphic rhabdomyoarcoma is the most common variety encountered. Rhabdoyosarcoma of the larynx tends to be less aggressive than habdomyosarcoma elsewhere in the head and neck region. lthough it is the most common soft tissue sarcoma in chilren, it ranks third in adults. Herein we report a case of mbryonal rhabdomyosarcoma involving the larynx as the nitial site of involvement.

Treatment of advanced soft tissue sarcomas with ifosfamide and doxorubicin combination chemotherapy.

Our objective was to assess the efficacy of a standard dose ifosfamide and doxorubicin containing regimen in the treatment of advanced soft tissue sarcomas. Forty consecutive patients with a median age of 35.5 years were treated. Ifosfamide was administered at a dose of 2.5 g/m2/day as 72‐hour continuous infusion with mesna at the same dosage and schedule. Doxorubicin was given at the dose of 60 mg/m2/day as 2‐hour infusion on day 1. Six patients had a complete response (15%), and 9 (22.5%) had a partial response, fourteen patients (35%) stable disease, and 11 (27.5%) did not respond to chemotherapy. The median duration of response was 13 and 5 months for the complete and partial responders, respectively. The median survival was 37 months. Febrile neutropenia was encountered in 9 cases (22.5%). The present ifosfamide and doxorubicin combination is a moderately effective and well‐tolerable regimen in the treatment of advanced soft tissue sarcomas. J. Surg. Oncol. 2000;73:12–16.