Prognostic factors associated with the response to sunitinib in patients with metastatic renal cell carcinoma.

OBJECTIVE: We investigated the prognostic clinicopathologic factors associated with overall survival (os) and progression-free survival (pfs) in the once-daily continuous administration of first-line sunitinib in a consecutive cohort of Turkish patients with metastatic renal cell carcinoma (rcc). METHODS: The study enrolled 77 Turkish patients with metastatic rcc who received sunitinib in a continuous once-daily dosing regimen between April 2006 and April 2011. Univariate analyses were performed using the log-rank test. RESULTS: Median follow-up was 18.5 months. In univariate analyses, poor pfs and os were associated with 4 of the 5 factors in the Memorial Sloan-Kettering Cancer Center (mskcc) score: Eastern Cooperative Oncology Group performance status of 2 or higher, low hemoglobin, high corrected serum calcium, and high lactate dehydrogenase. In addition to those factors, hypoalbuminemia, more than 2 metastatic sites, liver metastasis, non-clear cell histology, and the presence of sarcomatoid features on pathology were also associated with poor pfs; and male sex, hypoalbuminemia, prior radiotherapy, more than 2 metastatic sites, lung metastasis, nuclear grade of 3 or 4 for the primary tumour, and the presence of sarcomatoid features were also associated with poorer os. The application of the mskcc model distinctly separated the pfs and os curves (p < 0.001). CONCLUSIONS: Our study identified prognostic factors for pfs and os with the use sunitinib as first-line metastatic rcc therapy and confirmed that the mskcc model still appears to be valid for predicting survival in metastatic rcc in the era of molecular targeted therapy.

Human immunodeficiency virus-negative tonsil Kaposi's sarcoma and Hodgkin's disease: case report and review of the literature.

Kaposi's sarcoma (KS) is a multicentric malignant neoplastic vascular disorder characterized by multiple violet-colored nodules of the skin. The coexistence of KS with other primary malignancies, especially of the lymphoreticular system, has been frequently noted. However, the association of Hodgkin's disease with KS is a rare occurrence. In this article we present the case of a 33-year-old man with human immunodeficiency virus (HIV)-negative KS of the tonsil, occurring in the radiotherapy field for Hodgkin's disease treated 20 years ago.

Effect of field placement errors on dose at junction between divergence matching and half-beam block techniques in craniospinal irradiation.

PURPOSE: In craniospinal irradiation, both overlapping and gapping between the cranial and upper spinal field may occur due to patient's daily position (setup). This can cause dose inhomogeneities at the craniospinal junction. In this study we tried to find out possible dose changes at the craniospinal junction due to setup mistakes. MATERIALS AND METHODS: Both divergence matching technique (DMT) and half-beam block technique (HBBT) were used. At first step, a gap between cranial and spinal field borders was used, and at the second step overlapping between the fields for both techniques was applied. We irradiated films located in water equivalents solid phantoms with Co60 teletherapy machine. RESULTS: Dose homogeneity was 4% when no gap was used. When 2, 5, 8 and 10 mm gap were used, overlap occurred. Dose inhomogeneities were 6%, 17%, 27%,34% and 16%, 24%, 29%, 43%, respectively for DMT. Dose inhomogeneity was 5% with no gap used. With gaps of 2, 5, 8, and 10 mm, overlap occurred. Dose inhomogeneities were 8%, 12%, 36%, 51% and 17%, 29%, 35%, and 47%, respectively for HBBT. CONCLUSION: With no gap or with 2mm gap between the fields the dose homogeneity is in acceptable dose variation limits (10%) for both techniques (DMT and HBBT). Beyond this distance the setup mistakes are not tolerable.

Non-resective management of pineoblastoma.

The results of a non-resective treatment approach for pineoblastoma comprising stereotactic biopsy, cerebrospinal fluid diversion, and fractionated radiotherapy in six patients over a period of six years are presented. There were three male and three female patients, with a median age at diagnosis of 20 years. Magnetic resonance imaging of the spine, ventricular cerebrospinal fluid cytology, and tumour markers in cerebrospinal fluid were negative. Tumour response to initial radiotherapy was complete in three patients and partial in three patients. Recurrences were treated with interstitial irradiation with iodine-125 seeds in four instances, repeat radiotherapy when time elapsed was more than five years in one instance, with surgical resection in two instances, and chemotherapy in two instances. The diagnostic and therapeutic effectiveness of this management strategy is assessed. There were no complications related to surgical procedures. The median follow-up time was 48 months (range 14-70 months). Five patients were alive at 14, 45, 51, 57, and 70 months of follow-up. One patient died of disease at 28 months following diagnosis. The overall survival rate was 80 % +/- 17.89 % at 28 months. The results of this study suggest that this non-resective treatment approach is acceptable as an initial treatment alternative to radical surgical resection of pineoblastomas.

Prognostic significance of marker half-life during chemotherapy in non-seminomatous germ cell testicular tumors.

Decrease in serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) levels is considered as a response during chemotherapy of non-seminomatous germ cell testicular tumors, but data on the prognostic significance of marker half-life remains inconclusive. Serum marker half-life was evaluated in 34 patients with elevated markers, receiving chemotherapy (CT). Marker half-life was calculated from the natural logarithm of the sequential AFP or HCG concentrations. The correlation between event-free (EFS) and overall survival (OS) with unfavorable half-lives of AFP and HCG was evaluated. Median actual half-life (AHL) AFP was 3.9 days (range, 1.4-21.5) and median AHL HCG was 4.4 days (range, 1.4-21.0); 82% of the patients had a satisfactory initial decline in AFP, and 71% had a satisfactory initial decline in HCG. There was a significant difference in EFS and OS between the two groups of patients with an AFP half-life < 7 days and > 7 days. HCG half-life did not adversely affect EFS and OS. The correlation of better EFS and OS with appropriate AFP marker half-life during chemotherapy could provide a dynamic method, which could complement the standard baseline prognostic factors, for the prediction of prognosis.

A phase II trial, feasibility of combination of daily cisplatinum and accelerated radiotherapy via concomitant boost in stage III non-small cell lung cancer.

PURPOSE: A prospective phase II trial was conducted by the Institute of Oncology, Istanbul University in December 1994 on patients with locally-advanced non-small cell lung cancer to assess acute toxicity and the feasibility of a combination of radiosensitizer and accelerated radiotherapy with concomitant boost. MATERIALS AND METHODS: Patients were irradiated using 'large' fields (primary tumour and locoregional lymph nodes) with 1.8 Gy per fraction, five fractions a week. Reduced 'boost' fields (primary and involved nodes only) were also irradiated twice-weekly 1.8 Gy per fraction in ten fractions concomitantly 6 h after the administration of large field. Total radiation dose was 63 Gy in 5 weeks (45 Gy 'large' fields and 18 Gy 'boost'). The maximum allowed dose to the spinal cord was 3750 cGy. Cisplatinum, 6 mg/m2 was given daily just before 'large' field irradiation. RESULTS: As of January 1997, 15 patients were evaluated (median follow-up of 12.5 months with a range of 5.5-23 months). The overall acute toxicity rate was 38% and Grade 3 acute toxicity was 8%. Grade 4 or greater acute toxicities were not observed. The overall rate of cisplatinum-induced nausea and vomiting was 80% (severe in 60%), but all were easily treated with antiemetics. Complete response rate (clinical and radiological) was 40% and an overall response rate was 73%. Median survival was 16 months and progression-free survival was 5.5 months (range of 2.5-21 months). CONCLUSIONS: Toxicity was well tolerated and no treatment-related death occurred with this combined treatment regimen. Although it appears that better local control rates can be achieved, additional phase II/III studies are needed.

Microscopic local leptomeningeal invasion at diagnosis of medulloblastoma.

PURPOSE: To document the incidence and outcome of patients with microscopic local leptomeningeal invasion at presentation, children with medulloblastoma were reviewed. METHODS AND MATERIALS: Nineteen patients (1-12 years of age), who had surgical resection (14 total, 5 subtotal) and were diagnosed as medulloblastoma, were evaluated for disease extent by pre- and postoperative computerized tomography/magnetic resonance imaging, histopathologic evaluation of leptomeninges adjacent to the resected tumor tissue, myelography/magnetic resonance of the entire spine, and analysis of cerebrospinal fluid cytology. Patients were also reviewed for disease outcome. RESULTS: Staging revealed one T2, nine T3a, eight T3b, and one T4 disease. There were 10 M0, 2 M1, 2 M2, 2 M3, and 3 Mx patients according to Chang's classification. Ten out of 19 patients (52.6%) demonstrated microscopic local leptomeningeal invasion. When only the 10 patients with M0 disease were considered, three out of five patients with microscopic local leptomeningeal invasion was found to have one or more relapses. The five other M0 patients without microscopic local invasion were in complete remission at the time of analysis. CONCLUSION: The incidence of microscopic local leptomeningeal invasion in patients with medulloblastoma is high. Whereas the impact on survival remains to be determined in larger series, data suggests prognostic role for isolated microscopic local leptomeningeal invasion, thus validity for inclusion in the future staging system.

Hypertrophic osteoarthropathy and intrathoracic Hodgkin disease of childhood.

BACKGROUND: Hypertrophic osteoarthropathy (HOA), well known in adults, is rarely encountered in children. The clinical features include clubbing of the fingers and toes, arthritis, and painful periosteal new bone formation of the tubular bones. The association of malignant disorders with HOA is more common in adults than in children. CASE: In this paper, a 12-year-old boy with intrathoracic Hodgkin disease and HOA is presented and four other children with HOA and Hodgkin disease in the literature reviewed. DISCUSSION: The presence of HOA has been thought to be a bad prognostic sign, but complete remission of Hodgkin disease and regression of clinical signs and symptoms of HOA were attained in our patient after chemotherapy and radiotherapy, and continue during 9 months post-therapy follow-up. CONCLUSIONS: HOA accompanying a malignant tumor in children is very rare. Only 5 cases have been associated with Hodgkin disease, including the present boy. It is important that patients with symptoms of HOA and an intrathoracic mass be examined carefully to rule out a malignancy.

Plastic surgery in irradiated areas: analysis of 200 consecutive cases.

Reconstructive surgery in previously irradiated areas is more difficult than in non-irradiated cases. A retrospective analysis of the outcome of 200 previously irradiated patients who had skin graft or flap reconstruction performed by the same surgeon is presented, and the most suitable surgical technique in irradiated areas is discussed. One hundred and fifty-six patients had skin and oral cavity cancer, and were operated on after local recurrence. Twenty patients had breast cancer; 15 were operated on for local recurrence and five for breast reconstruction. Twenty-four patients had soft tissue sarcomas. Eighty-five patients had a skin graft (group 1), 35 had a skin flap (group 2), 10 had a fascia/muscle flap plus skin graft and 70 had a myocutaneous flap (group 3). Analysis of complications revealed statistically significant differences in terms of incomplete graft/flap necrosis between group 1 and 2 (P < 0.001) and groups 1 and 3 (P < 0.001), and in terms of infection between groups 1 and 3 (P < 0.01). We conclude that the method of reconstruction is determined by the characteristics of the defect such as size and localization; the quality, fractionation, total dose, and energy of radiation used; skin and subcutaneous tissue changes due to radiation; and operation time. However, it is reasonable to choose fascia/muscle or myocutaneous flaps for reconstruction in previously irradiated areas. These methods are more resistant to bacterial inoculation, more prone to clean residual infection, and provide better vascularized tissue and volume replacement for contour defects.

Primary spinal column sarcomas.

Five cases of primary spinal column sarcomas are presented. Sarcomas primarily originating from paravertebral soft tissues were excluded. Patients' age ranged from 1 to 14 years (mean 8.4 years). The male:female ration was 2:3. Two patients had Ewing's sarcoma (ES) originating from L5-S1 and L4-5 pedicles, respectively; two patients had mesenchymal chondrosarcoma (MCS) originating from L1-2 pedicles and L5 body, respectively; and one patient had osteogenic sarcoma (OS) of C4 body. All patients clinically presented with pain and progressive weakness of the extremities. The time that elapsed between the onset of symptoms and diagnoses ranged from one to five months. All cases were treated with chemotherapy, radiotherapy and subtotal tumour resection with spinal canal decompression. Two cases received posterior spinal fusion operations. Three patients were alive 10 to 98 months following diagnosis. Only the case with ES of L5-S1 pedicles was in complete remission and off therapy at the 98th postoperative month. The two MCS cases were in partial remission, and were receiving chemotherapy at the time of analysis. These tumours caused similar clinical findings and prognoses, and required combined treatment, which consisted of surgery, radiotherapy and chemotherapy; histologically three different types of malignant tumours are presented in the same category. We preferred surgical decompression and stabilization procedures especially for neurologically symptomatic patients, even if they had extensive tumours with high grades. By spinal canal decompression and stabilisation, we did not intend to cure the disease; however, we intended to provide neurological improvement, spinal stabilisation, improved quality of life, early mobilisation of the patient, and cytoreduction by means of surgical tumour ablation, which could render the chemotherapy more effective.

Evaluation of response to postradiation eight in one chemotherapy in childhood brain tumors.

Ten children, 3 to 15 years of age with high risk primary brain tumors were treated with postradiation 'eight in one' chemotherapy; vincristine, lomustine, procarbazine, hydroxyurea, cisplatin, cytosine arabinoside, cyclophosphamide and methylprednisolone. The tumors comprised of three medulloblastomas, two primitive neuroectodermal tumors, one ependymoblastoma and four anaplastic ependymomas. Treatment involved surgery (two total resection, six subtotal and two biopsy only) followed by conventional radiotherapy (primary tumor: 50-54 Gy, whole brain: 30-45 Gy, and spinal axis: 25-36 Gy). Objective tumor response with radiotherapy was achieved in 7 of 9 patients (78%) (6/8 patients with residual tumor and one patient with complete resection but positive cerebrospinal fluid cytology). Complete response was attained in 4 of 9 patients (44%). 'Eight in one' chemotherapy was initiated four weeks after radiation and repeated at 4 weekly intervals for 5-8 courses. Postradiation 'eight in one' failed to show any additional effect on tumor responses. Median survival was 34 months (range 9-48 months) with five of ten patients alive: four in complete and one in partial remission. All the five survivors were among the patients who had achieved response to initial treatment. This result suggested that degree of response to initial treatment might determine subsequent outcome and thus the choice of modality for initial therapy might be important.

Immunologic status in children with brain tumors and the effect of therapy.

The cellular and humoral immunological parameters (leucocyte, granulocyte, lymphocyte, total T, T4, T8 lymphocyte counts, lymphoproliferative response to PHA [LP-PHA], natural killer cell activity [NKCA], IgG, IgM and IgA levels) of 20 pediatric brain tumor patients were investigated before and after chemo-(CT) and radiotherapy (RT) administered according to the UIOI-PBT-91 protocol. The T4 and T8 cell percentages and the LP-PHA values before therapy were found to be significantly diminished in comparison to values obtained from 12 healthy children (p < 0.05). In patients receiving postoperative CT, all cellular immunity parameters except T8 cell number and NKCA; IgG and IgA levels were significantly decreased after two courses of CT (p < 0.05). In 7 patients given postoperative RT, a depression in all cellular immunity parameters was observed (p < 0.05). In 6 patients treated with 2 courses of postoperative CT followed by RT administered concomitantly with low dose CDDP, there was a decrease in all cellular and humoral immunity parameters, which was not found to be significant. In 5/18 patients infectious episodes in mild to moderate severity were observed, none causing mortality. It was concluded that the UIOI-PBT-91 protocol caused cellular immunosuppression both after CT and after RT and some humoral immunosuppression after CT, but was found to be tolerable in regard to acute immunological side effects.

Epidural metastasis in Wilms' tumor: a case report and review of the literature.

Spinal canal involvement is not a common pattern of metastasis in Wilms' tumor. Although early detection and treatment can achieve improvement of neurological deficit, mortality remains high. We present a 5-year-old girl who had an epidural metastasis while she was receiving chemotherapy for stage IV Wilms' tumor. Within 2 months following laminectomy, total removal of tumor, radiotherapy, and adjuvant chemotherapy some of the neurological signs improved.

Primary osteosarcoma of the cervical spine: a pediatric case report and review of the literature.

A 4 1/2-year-old girl with a primary osteosarcoma of the seventh cervical vertebra, treated by surgery and chemotherapy, and who is off therapy for 24 months with no evidence of disease is presented and the literature reviewed.

Non-midline endodermal sinus tumor in the head and neck region: a case report.

Germ cell tumors, in particular teratomas, are some of the most commonly found tumors in childhood. Six percent of all germ cell tumors are located in the head and neck region. Endodermal sinus tumors (yolk sac tumors) of the head and neck, exclusive of the central nervous system, are rare. This study reports a 20-month-old girl with a mass of 5 x 5 cm on the left temporal area and with bone destruction on CT. The histopathological examination of the excised mass revealed an endodermal sinus tumor. The serum AFP and the LDH levels were elevated at diagnosis. The patient was treated by the BEP protocol (bleomycin, etoposide, and cisplatin), six cycles every three weeks. Partial response was attained after the first and complete response after the fourth cycle. The patient, who is being followed up, has been in remission for five months.