Kinetic modeling of tumor growth and dissemination in the craniospinal axis: implications for craniospinal irradiation

BACKGROUND: Medulloblastoma and other types of tumors that gain access to the cerebrospinal fluid can spread throughout the craniospinal axis. The purpose of this study was to devise a simple multi-compartment kinetic model using established tumor cell growth and treatment sensitivity parameters to model the complications of this spread as well as the impact of treatment with craniospinal radiotherapy. METHODS: A two-compartment mathematical model was constructed. Rate constants were derived from previously published work and the model used to predict outcomes for various clinical scenarios. RESULTS: The model is simple and with the use of known and estimated clinical parameters is consistent with known clinical outcomes. Treatment outcomes are critically dependent upon the duration of the treatment break and the radiosensitivity of the tumor. Cross-plot analyses serve as an estimate of likelihood of cure as a function of these and other factors. CONCLUSION: The model accurately describes known clinical outcomes for patients with medulloblastoma. It can help guide treatment decisions for radiation oncologists treating patients with this disease. Incorporation of other treatment modalities, such as chemotherapy, that enhance radiation sensitivity and/or reduce tumor burden, are predicted to significantly increase the probability of cure

Combined treatment modality for intracranial germinomas: results of a multicentre SFOP experience

Conventional therapy for intracranial germinomas is craniospinal irradiation. In 1990, the Société Française d'Oncologie Pédiatrique initiated a study combining chemotherapy (alternating courses of etoposide–carboplatin and etoposide–ifosfamide for a recommended total of four courses) with 40 Gy local irradiation for patients with localized germinomas. Metastatic patients were allocated to receive low-dose craniospinal radiotherapy. Fifty-seven patients were enrolled between 1990 and 1996. Forty-seven had biopsy-proven germinoma. Biopsy was not performed in ten patients (four had diagnostic tumour markers and in six the neurosurgeon felt biopsy was contraindicated). Fifty-one patients had localized disease, and six leptomeningeal dissemination. Seven patients had bifocal tumour. All but one patient received at least four courses of chemotherapy. Toxicity was mainly haematological. Patients with diabetus insipidus (n = 25) commonly developed electrolyte disturbances during chemotherapy. No patient developed tumour progression during chemotherapy. Fifty patients received local radiotherapy with a median dose of 40 Gy to the initial tumour volume. Six metastatic patients, and one patient with localized disease who stopped chemotherapy due to severe toxicity, received craniospinal radiotherapy. The median follow-up for the group was 42 months. Four patients relapsed 9, 10, 38 and 57 months after diagnosis. Three achieved second complete remission following salvage treatment with chemotherapy alone or chemo-radiotherapy. The estimated 3-year survival probability is 98% (CI: 86.6–99.7%) and the estimated 3-year event-free survival is 96.4% (CI: 86.2–99.1%). This study shows that excellent survival rates can be achieved by combining chemotherapy and local radiotherapy in patients with non-metastatic intracranial germinomas. © 1999 Cancer Research Campaig

Permanent ¹²⁵I prostate brachytherapy outcome in patients younger than 60

14553 Background: Permanent 125I prostate brachytherapy (PB) has been shown to be an effective form of treatment for men with clinically localized prostate cancer. However, the efficacy of PB in younger men is not well established, and many urologists and oncologists have been reluctant to recommend PB to younger men, since most reported PB outcome has been based on men implanted in their late 60s and 70s. Methods: Between 1/1/98 and 6/30/01, 100 consecutive men aged 49–59 (median 56) underwent PB. All had either low- or intermediate-risk disease. PB was performed without combined external beam irradiation or post-PB androgen deprivation. The prescribed radiation dose=144–145Gy, the median implant activity=38mCi, median prostate volume=36 ml. Mean day-30 post-PB CT-based implant dosimetry values were V100=94%; V150=60%; D90=160 Gy. The primary endpoint for this analysis was the 5-year biochemical no evidence of disease rate (bNED) defined by the ASTRO consensus definition. Secondary endpoints were disease-specific survival (DSS); freedom from salvage therapy (FSRx), and overall survival (OS). Median PSA followup was 59 months (maximum 93 months). Actuarial results were calculated using the Kaplan-Meier method. Results: The 5-year bNED rate was 92%. 8 patients developed biochemical failure, and 6 went on to salvage treatment with hormonal therapy. There were 2 biopsy-proven local recurrences: one in a patient with previously diagnosed bony metastases, and one with isolated seminal vesicle recurrence (prostate biopsies negative). 3 other patients with biochemical failure had negative re-biopsies at 24, 64, and 66 months post-PB. No patient received local salvage therapy. One patient died from a second malignancy (colon CA diagnosed after PB). The 5-year DSS rate = 100%; FSRx = 93%, and OS = 99%. There were 2 Grade 3 GU complications (urethral strictures) (2%) and one Grade 4 GU complication (TURP) (1%). There were no Grade 3 or 4 GI complications. Conclusions: PB is an effective treatment modality for men younger than 60, with 5 year results comparable to those reported with prostatectomy and external beam irradiation. Given that most men who fail PB do so within 5 years of the implant, there appears to be no compelling scientific reason to advise against PB in men younger than 60 solely based on their age. No significant financial relationships to disclose. </jats:p