Long-term follow-up confirms the efficacy of linac radiosurgery for acoustic neuroma and meningioma patients. A single institution's experience.

PURPOSE: To investigate the long-term efficacy and toxicity in a group of consecutive patients treated with linear accelerator (linac) radiosurgery for acoustic neuromas and meningiomas. METHODS: Between 2000 and 2004, 34 patients (median age 65.5 years, range 50-84) with acoustic neuroma or meningioma were treated with linac-based stereotactic radiosurgery with a surface dose of 11-15.5 Gy. The maximum lesion diameter ranged from 10 to 34 mm. Median tumor volume was 5.95cm(3). The follow-up consisted of repeated imaging studies and clinical examination in the first 6 and 12 months after the intervention and yearly thereafter. RESULTS: Follow-up time ranged from 50 to 99 months (median 75). Nineteen (59%) tumors decreased in size and 13 (41%) remained stable. None of the tumors increased in size in the long-term follow-up, resulting in an overall growth control of 100% for the small number of patients of our study. No patient developed new permanent facial or trigeminal neuropathy or deterioration of preexisting symptoms. CONCLUSION: Long-term follow-up confirms the efficacy and low toxicity of linac radiosurgery for neuroma and meningioma patients.

Brain metastases as isolated site of relapse in patients with epithelial ovarian cancer previously treated with platinum and paclitaxel-based chemotherapy.

Brain metastases in patients with epithelial ovarian cancer (EOC) have an estimated incidence of 0.3-1.9% and are isolated in up to 50% of these patients. The risk factors and the prognostic significance of isolated central nervous system (CNS) relapse in patients with EOC who received primary treatment with platinum and paclitaxel have not been identified. We conducted a retrospective study in patients with EOC who relapsed with isolated brain metastases and report our experience. Two hundred sixty-seven patients with stages III and IV EOC, in clinical complete remission after first-line treatment with platinum and paclitaxel, were included in our analysis. After a median follow-up of 65 months, 150 patients had relapsed. Eight patients (5%) had isolated brain metastases. Patient and disease characteristics did not differ among patients who relapsed with isolated brain metastases and those with relapse outside the CNS. Median time to first disease relapse, overall survival, and survival after relapse did not differ significantly between patients with brain metastases and those with relapse outside the CNS. Two patients have died 6 and 12 months after the diagnosis of brain metastases, and 5 patients are alive 4-35 months after the diagnosis of isolated brain metastases. Three patients remain free of disease 4-18 months after treatment with radiotherapy and systemic chemotherapy for their CNS metastatic disease. Patients with isolated brain metastases have comparable survival to patients with relapse outside the CNS, and long-term remission can be achieved in some cases, provided that systemic chemotherapy is added to local treatment.

Intramedullary spinal cord and leptomeningeal metastases in a patient with carcinoma of the uterine cervix.

BACKGROUND: : Neoplastic meningitis in patients with carcinoma of the uterine cervix is unusual in the course of their diseases. Even more unusual are intramedullary spinal metastases. CASE: We report the case of a 64-year-old woman who presented with leptomeningeal and intramedullary spinal cord metastases from a grade 2 squamous cell cancer of the uterine cervix. This is just the second case of intramedullary metastases from cervical carcinoma. CONCLUSION: Neoplastic meningitis or intramedullary metastases are extremely rare in the course of uterine cervix carcinoma. Nevertheless, when indicated by symptoms, patients should undergo MRI of the brain and/or spine and have a lumbar puncture performed, for the diagnosis of this devastating complication. Treatment is mainly palliative but may offer symptom relief.

Oral pseudomembranous candidiasis, herpes simplex virus-1 infection, and oral mucositis in head and neck cancer patients receiving radiotherapy and granulocyte-macrophage colony-stimulating factor (GM-CSF) mouthwash.

Oral pseudomembranous candidiasis (OPC) was evaluated in 61 patients receiving head and neck radiotherapy (RT). Herpes simplex virus-1 (HSV-1) reactivation was also investigated in 14 patients. According to the agreed protocol, granulocyte-macrophage colony-stimulating factor (GM-CSF) mouthwash was administered in 46 patients with radiation-induced ulcers. Candidiasis was diagnosed in 31 patients. Candida albicans was the most frequent isolate. Multiple Candida species were isolated from the lesions of four patients. Concurrent candidiasis and radiation-induced ulcers were observed in 17 patients. Viral culture and the polymerase chain reaction disclosed the presence of HSV-1 in five patients. Twenty of the 46 patients, with initial mucositis grade II and grade III, completed RT with mucositis grade I, indicating a beneficial effect of GMCSF mouthwash, although further controlled studies are necessary to verify that. In conclusion, OPC was an important infection in patients undergoing radiotherapy. The role of HSV-1 in oral mucositis during head and neck radiotherapy needs additional study.

Squamous cell head and neck cancer: evidence of angiogenic regeneration during radiotherapy.

BACKGROUND AND PURPOSE: Intra-tumoural neoangiogenesis is an essential process for tumour progression. Although intensification of angiogenic pathways during cytotoxic therapy has been reported by a few experimental studies, the role of angiogenesis in response to radiotherapy is unclear. We recently reported an adverse effect of intense angiogenesis in the radiotherapy outcome of squamous cell head and neck cancer (SCHNC). In the present study we investigated the radiotherapy-induced changes in the microvessel density (MVD) and in the expression of the angiogenic factor thymidine phosphorylase (TP) in SCHNC. PATIENTS AND METHODS: Twenty-four patients with SCHNC underwent a biopsy of the primary lesion immediately before and after delivery of 20Gy of conventionally fractionated radiotherapy. The MVD and the expression of TP was assessed with immunohistochemistry. RESULTS: The irradiated samples were composed of cancer cell islets or bands, immersed within avascular degenerated tissue. In tumours that did not reach complete response after the end of radiotherapy, these viable cancer tissue areas had a significantly higher MVD (p=0.006) and increased percentage of cancer cells with nuclear TP expression (p=0.0004) than the MVD and the TP expression noted in specimens before radiotherapy. TP expression in these islets was directly related to the MVD (p=0.004, r=0.56). CONCLUSION: The present study supports the idea that intensified angiogenic growth (angiogenic regeneration) during radiotherapy is associated with failure of radiotherapy.

Cathepsin D may help in discriminating node-negative breast cancer patients at risk for local-regional recurrence.

OBJECTIVE: The objective of this retrospective study was to define the prognostic value of cathepsin D (CD) in the node-negative (N-) and node-positive (N+) subsets of breast cancer (BC) patients. PATIENTS AND METHODS: In primary tumor cytosols of 348, stage I-III, BC patients, with a complete standard histological examination and a 56 months mean follow-up, the ER, PR and CD concentrations were measured by standardized assays. CD values were then compared to the classical prognostic factors, the type of treatment and the outcome, in terms of Disease-Free-Survival (DFS) and type of Relapse, after stratification according to the nodal status. Statistical methods used were Cox regression and logistic regression. RESULTS: Using univariate analysis, CD > 60 pmol/mg prot in N- patients was significantly associated with shorter DFS as well as local-regional recurrence (LRR) while in multivariate analysis the same CD levels, together with T status, are the best predictors of short DFS. However, CD > 60 is the only potent predictor of LRR in N- patients. No prognostic value of CD was identified in N+ patients. The cutoff value of CD should be 60 pmol/mgprot. The combination of tumor size, ER status and CD concentration may yield reliable prediction of primary BC outcome in N- patients. CONCLUSION: CD is a marker of invasiveness, particularly loco-regional in node-negative breast cancer. The integration of this marker, in the routine of initial prognostic evaluation of this subset of patients is proposed.

Relationships between cathepsin-D, pS2 protein and hormonal receptors in breast cancer cytosols: inconsistency with their established prognostic significance.

In this study the unexpected findings from the analysis of 278 breast cancer tissue specimens are reported. A surprising strongly positive correlation between an unfavourable and a favourable prognosis with markers cathepsin D and pS2 respectively, was revealed by linear regression analysis (Pearson, Student-T-Test). In the relevant literature reviewed only one similar, although indirect, observation was found. On the other hand, a weak relationship between pS2 and ER has emerged using the same method, while the pS2/PgR association remained strong. The latter supports the hypothesis that pS2 positivity is associated with positive PgR and may be a marker of functioning ER, irrespective of ER status. These and other similar findings underline the need for a better understanding of the underlying molecular events as well as the necessity of an effective prognostic evaluation model for breast cancer.

Cathepsin D concentration in tumor cytosols improves the accuracy of prognostic evaluation of primary breast cancer.

One hundred and seventy three women were followed-up for a median of 62 months after surgery for Stage I-III breast cancer. The concentration of cathepsin D (CD) in tumor cytosols was compared to the standard prognostic factors for the disease and related to relapse free and overall survival and type of relapse. Three groups were identified with different prognostic profile. High CD levels significantly shorten DFS in both node-negative and node-positive patients; a correlation between high cathepsin D levels and locoregional relapse should also be noted. This marker should be included in the initial evaluation of breast cancer as an indicator of invasiveness.

Unresectable colorectal-carcinoma - 10 years experience with patients treated with radical or palliative external-beam radiotherapy in Greece.

Our analysis presents a group of 86 patients with unresectable colorectal cancer who were treated with radical or palliative external beam radiotherapy from 1979-1990 at the Radiation Oncology Department of Greek Anticancer Institute, St. Savvas Hospital, Athens. The dose applied to the tumor area was 20-50 Gy in 2-6 weeks. A CAT-scan guided boost field portal to the primary tumor bed and immediately adjacent nodes was also used. Irradiation was given with a Co-60 unit or a 6 MeV Linear Accelerator using a two, three or 4-field technique. Complete symptomatic relief was achieved in 90% of patients with rectal bleeding, 63% with pain and 37% with mucous discharge. Although the majority of our patients received a higher than 40Gy radiation dose, we have seen symptomatic relief in up to 90% of patients treated with 20-30 Gy in 2-3 weeks. However, the duration of improvement in symptomatic relief of our patients was better for those who had been given higher doses of radiation therapy. The radiation dose was sufficient to relieve symptoms in 40 patients (46.5%) for more than 12 months and in 20 patients (23.2%) for 8-12 months.