Ibrahim Gullu

Salvage reirradiaton with stereotactic body radiotherapy for locally recurrent head-and-neck tumors.

PURPOSE In this study, we present our results of reirradiation of locally recurrent head-and-neck cancer with image-guided, fractionated, frameless stereotactic body radiotherapy technique. METHODS AND MATERIALS From July 2007 to February 2009, 46 patients were treated using the CyberKnife (Accuray, Sunnyvale, CA) at the Department of Radiation Oncology, Hacettepe University, Ankara, Turkey. All patients had recurrent, unresectable, and previously irradiated head-and-neck cancer. The most prominent site was the nasopharynx (32.6%), and the most common histopathology was epidermoid carcinoma. The planning target volume was defined as the gross tumor volume identified on magnetic resonance imaging and computed tomography. There were 22 female and 24 male patients. Median age was 53 years (range, 19-87 years). The median tumor dose with stereotactic body radiotherapy was 30 Gy (range, 18-35 Gy) in a median of five (range, one to five) fractions. RESULTS Of 37 patients whose response to therapy was evaluated, 10 patients (27%) had complete tumor regression, 11 (29.8%) had partial response, and 10 (27%) had stable disease. Ultimate local disease control was achieved in 31 patients (83.8%). The overall survival was 11.93 months in median (ranged, 11.4-17.4 months), and the median progression free survival was 10.5 months. One-year progression-free survival and overall survival were 41% and 46%, respectively. Grade II or greater long-term complications were observed in 6 (13.3%) patients. On follow-up, 8 (17.3%) patients had carotid blow-out syndrome, and 7 (15.2%) patients died of bleeding from carotid arteries. We discovered that this fatal syndrome occurred only in patients with tumor surrounding carotid arteries and carotid arteries receiving all prescribed dose. CONCLUSIONS Stereotactic body radiotherapy is an appealing treatment option for patients with recurrent head-and-neck cancer previously treated with radiation to high doses. Good local control with considerable 1-year survival is achieved with a relatively high rate of morbidity and related mortality.

Malignancy in Behçet’s Disease: A Report of 13 Cases and a Review of the Literature

Abstract Behçet’s disease (BD) has rarely been reported in association with malignant diseases. In most cases the autoimmune nature of the disease itself or immunosuppressive drug use has been blamed for malignant transformation. We report 13 cases of BD concurrent with neoplastic disease as well as treatment-related morbidities in this particular patient group. Between 1986 and 1999, 400 patients were diagnosed as having BD in Hacettepe University Hospitals. Of these 13 patients, 3.25% developed malignant diseases within a median follow-up time of 9.8 years. Solid tumors were diagnosed in 10 patients and haematological or lymphoid malignancies in three. Surgery was performed in seven patients, whereas radiotherapy was applied in six and chemotherapy in eight. A literature review revealed 27 cases of BD associated with malignancies, mostly lymphoid or haematological. Ten of our cases were solid tumors, and to our knowledge most of these are the first reported cases of specific malignancies concurrent with BD. Treatment-related morbidities were wound infection as surgical morbidity in one patient (1/7) and radiotherapy-related morbidity in three (3/6) patients in a median follow-up time of 2 years. Solid tumors in addition to lymphoid and haematological malignancies are also seen during the course of BD. Radiation therapy may cause severe late toxicities in the presence of BD. Chemotherapy and surgery are fairly safe for the treatment of malignancies in BD patients.

Old antihypertensives as novel antineoplastics: angiotensin-I-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists

Angiogenesis, cellular growth and invasion of a cancer cell are attractive targets for new treatment strategies of malignancies in recent years. The evidences are accumulating that ACE inhibitors and angiotensin II type 1 antagonists could be novel anti-angiogenic, anti-invasive, and even anti-growth agents against neoplastic tissues: The renin-angiotensin system promotes angiogenesis directly or indirectly and growth of neoplastic cell. Some tumors carry angiotensin II type 1 receptors. Angiotensin II antagonists and angiotensin-I-converting enzyme inhibitors have shown some anti-neoplastic actions. Angiotensin II receptor blocker losartan antagonises platelets, which are thought to modulate via vascular endothelial growth factor. They may even protect the patient from the major toxicity of chemotherapy and/or radiotherapy, myelotoxicity, enabling us to give higher doses and end up with higher success rate. We believe that these agents can be useful on clinical grounds and suggest their incorporation into clinical studies.

Primary Breast Lymphomas: A Retrospective Analysis of Twelve Cases

This study was undertaken to define the natural history and treatment results of patients with primary breast non-Hodgkins lymphoma (NHL). Twelve female patients who had been followed at Hacettepe University Hospital between 1973 and 1997 were retrospectively evaluated. All patients presented with breast masses (6 in the right breast and 6 in the left) that had recently enlarged. The most common histologic subtype was diffuse, small cleaved-cell lymphoma. Chemotherapy regimens were employed in 9 patients. Radiotherapy was delivered to the breast and its lymphatics in 8 patients. Lumpectomy, simple or modified radical mastectomy was performed in 5 cases. An objective response was attained with surgery, chemotherapy, or radiotherapy alone in 2, 1, and 1 cases, respectively. Combined modality treatment including either two or three modalities was successful in 7 cases. The median progression-free and overall survival times were 49 and 56 months, respectively. Although primary NHL of the breast is a rare disease compared to carcinoma, it should be considered in the differential diagnosis of breast masses.

Induction chemotherapy with cisplatin and 5-fluorouracil followed by chemoradiotherapy or radiotherapy alone in the treatment of locoregionally advanced resectable cancers of the larynx and hypopharynx: Results of single-center study of 45 patients

Induction chemotherapy with cisplatin and fluorouracil and radiotherapy is an effective alternative to surgery in patients with carcinoma of the larynx and hypopharynx who are treated for organ preservation.

A Retrospective Comparison of Robotic Stereotactic Body Radiotherapy and Three-Dimensional Conformal Radiotherapy for the Reirradiation of Locally Recurrent Nasopharyngeal Carcinoma

PURPOSE We assessed therapeutic outcomes of reirradiation with robotic stereotactic radiotherapy (SBRT) for locally recurrent nasopharyngeal carcinoma (LRNPC) patients and compared those results with three-dimensional conformal radiotherapy (CRT) with or without brachytherapy (BRT). METHODS AND MATERIALS Treatment outcomes were evaluated retrospectively in 51 LRNPC patients receiving either robotic SBRT (24 patients) or CRT with or without BRT (27 patients) in our department. CRT was delivered with a 6-MV linear accelerator, and a median total reirradiation dose of 57 Gy in 2 Gy/day was given. Robotic SBRT was delivered with CyberKnife (Accuray, Sunnyvale, CA). Patients in the SBRT arm received 30 Gy over 5 consecutive days. We calculated actuarial local control and cancer-specific survival rates for the comparison of treatment outcomes in SBRT and CRT arms. The Common Terminology Criteria for Adverse Events v3.0 was used for toxicity evaluation. RESULTS The median follow-up was 24 months for all patients. Two-year actuarial local control rates were 82% and 80% for SBRT and CRT arms, respectively (p = 0.6). Two-year cancer-specific survival rates were 64% and 47% for the SBRT and CRT arms, respectively (p = 0.4). Serious late toxicities (Grade 3 and above) were observed in 21% of patients in the SBRT arm, whereas 48% of patients had serious toxicity in the CRT arm (p = 0.04). Fatal complications occurred in three patients (12.5%) of the SBRT arm, and four patients (14.8%) of the CRT arm (p = 0.8). T stage at recurrence was the only independent predictor for local control and survival. CONCLUSION Our robotic SBRT protocol seems to be feasible and less toxic in terms of late effects compared with CRT arm for the reirradiation of LRNPC patients.

Serum lactate dehydrogenase level is a prognostic factor in patients with locoregionally advanced nasopharyngeal carcinoma treated with chemoradiotherapy.

We investigated the treatment results and probable prognostic factors in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) treated with neoadjuvant chemotherapy (NCT) plus conventional radiotherapy (RT) or concomitant chemoradiotherapy (CCRT) at our hospital. We retrospectively evaluated 61 patients (48 males, 13 females) with locoregionally advanced NPC treated either with 2 cycles of NCT plus RT (Group A, 37 patients) or with three cycles of NCT plus CCRT (Group B, 24 patients) between September 1995 and October 2002. According to the AJCC 1997 classification system, 19 patients had Stage III disease and 42 had Stage IV. NCT consisted of cisplatin and 5-fluorouracil. Total RT doses were ranged between 59.4–71.6 Gy (median: 66.2 Gy). Concomitant cisplatin (75 mg/m2) was given on first days of Weeks 1, 4, 7 of CCRT. Patient sex, histopathologic subtype, T status, ECOG performance status, stage, serum lactate dehydrogenase (LDH) level, and cranial nerve involvement at diagnosis were comparable in the 2 groups. There were statistically significant differences between median follow-up times and N status for the 2 groups. Fifty-five (90.2 percent) patients completed all planned NCT. Univariate analysis revealed the pretreatment LDH level as the only statistically significant prognostic factor for disease-free survival (DFS) and overall survival (OS). Four-year DFS rates were 55.9 percent and 21.3 percent for patients with normal and high serum LDH levels, respectively (P = 0.04). Four-year OS rates were 68.7 percent and 28.5 percent for patients with normal and high serum LDH levels, respectively (P = 0.01). Multivariate analysis also revealed that high serum LDH level was the only independent risk factor that predicted OS. The relative risk was 2.43 (95%CI: 1.08–5.45) for patients with high serum LDH levels (P = 0.03). No independent risk factors associated with DFS were found for other prognosticators. Our study demonstrated that high serum LDH level is the only independent unfavorable risk factor for OS in patients with locoregionally advanced NPC who were treated with NCT plus RT or CCRT.

Characteristics of Breast Cancer Patients with Central Nervous System Metastases: A Single-Center Experience

The aim of this study was to assess the characteristics of breast cancer patients with central nervous system (CNS) metastases and factors associated with survival after development of CNS metastasis. One-hundred-forty-four patients with brain metastases were retrospectively analyzed. Median age at the time of brain metastasis diagnosis was 48.9. Median time between initial diagnosis and development of brain metastasis was 36 months. Fourteen cases had leptomeningeal involvement. Twenty-two patients (15.3%) had single metastasis. Ten percent of the patients had surgery, 94% had radiotherapy and 63% had chemotherapy. Median survival after development of brain metastasis was 7.4 months. Survival of patients with single metastasis was significantly longer than those with multiple metastases (33.5 vs. 6.5 months, p = 0.0006). Survival of patients who received chemotherapy was significantly longer than those who received radiotherapy alone (9.9 vs. 2 months, p < 0.0001). In multivariate Cox regression analyses, presence of single metastasis and application of chemotherapy were the only significant factors associated with better survival (p = 0.047 and p < 0.0001, respectively). Age at initial diagnosis or at the time of brain metastasis, time from initial diagnosis to development of brain metastasis, menopausal status, tumor stage, grade, hormone receptor or HER2 status individually were not associated with survival. In this study, survival after the diagnosis of CNS metastases appeared to be affected by patient characteristics rather than biologic characteristics of the tumor. This is probably secondary to the lack of effective treatment options in these patients and overall poor prognosis.

Salvage ifosfamide-doxorubicin chemotherapy in patients with recurrent nasopharyngeal carcinoma pretreated with Cisplatin-based chemotherapy.

This study evaluated the efficacy and toxicity of ifosfamide and doxorubicin chemotherapy regimen in Turkish patients with recurrent or metastatic nasopharyngeal carcinoma (NPC) previously treated with platinum-based chemotherapy. Twenty-one patients with recurrent or metastatic NPC previously treated with platinum-based chemotherapy as adjuvant or palliative treatments who received ifosfamide 2500 mg/m2 d 1–3, mesna 2500 mg/m2 d 1–3, doxorubicin 60 mg/m2 d 1, repeated every 21 d was retrospectively analyzed. Patients received a median number of three cycles of ifosfamide-doxorubicin (range: 1–6). Seven patients (33.3%) achieved partial response and no patient achieved complete response. Six (28.5%) had stable disease, whereas three (18.75%) had progressive disease. The median time to progression was 7.0 mo. Ifosfamide-doxorubicin regimen is an effective salvage regimen in patients with recurrent and metastatic NPC.

Serum L-selectin and P-selectin levels in lymphomas.

The migration of normal and malignant lymphoid cells is governed by specific adhesion molecules. Selectins comprise a family of adhesion receptors expressed by leukocytes, platelets and endothelial cells. In this study, the serum levels of soluble L-selectin and P-selectin were measured in patients with non-Hodgkins lymphoma and Hodgkins disease and found to be significantly elevated in both patient groups compared to healthy controls. This result provides evidence that alterations in the expression and function of adhesion molecules may play an important role in the progression of lymphomas. Further studies are awaited to establish the exact roles of these adhesion molecules in distinct patterns of growth and spread of lymphomas.