Michael Milosevic

Oxygenation predicts radiation response and survival in patients with cervix cancer

BACKGROUND AND PURPOSE Hypoxia appears to be an important factor in predicting tumor relapse following radiation therapy. This study measured oxygenation prior to treatment in patients with cervix cancer using a polarographic oxygen electrode to determine if oxygenation was an important prognostic factor with regard to tumor control and survival. MATERIALS AND METHODS Between May 1994 and June 1997, 74 eligible patients with cervix cancer were entered into an ongoing prospective study of tumor oxygenation prior to primary radiation therapy. All patients were evaluated with an Eppendorf oxygen electrode during examination under anesthesia. Oxygenation data are presented as the hypoxic proportion, defined as the percentage of pO2 readings of <5 mm Hg (abbreviated as HP5). RESULTS The HP5 ranged from 2 to 99% with a median of 52%. With a median follow-up of 1.2 years, the disease-free survival (DFS) rate was 69% for patients with HP5 of < or =50% compared with 34% for those with HP5 of >50% (log-rank P = 0.02). Tumor size above and below the median of 5 cm was also significantly related to DFS (P = 0.0003) and patients with bulky hypoxic tumors had a significantly lower DFS (12% at 2 years) than either bulky oxygenated or non-bulky oxygenated or hypoxic tumors (65%, P = 0.0001). CONCLUSIONS Hypoxia and tumor size are significant adverse prognostic factors in a univariate analysis of disease-free survival in patients with cervix cancer. A high risk group of patients with bulky hypoxic tumors have a significantly higher probability of relapse and death.

Randomized study of brachytherapy in the initial management of patients with malignant astrocytoma.

PURPOSE A randomized study was undertaken to assess the role of brachytherapy as a boost to external beam radiation therapy in the initial management of patients with malignant astrocytomas. METHODS AND MATERIALS Inclusion criteria included the following: biopsy-proven supratentorial malignant astrocytoma of brain < or =6 cm in size, not crossing midline or involving corpus callosum, age 18-70, Karnofsky Performance Status (KPS) > or =70. Patients were randomized to external radiation therapy only delivering 50 Gray (Gy) in 25 fractions over 5 weeks or external radiation therapy plus a temporary stereotactic iodine-125 implants delivering a minimum peripheral tumor dose of 60 Gy. Patients were stratified to age < or =50 or >50, and KPS > or =90 or < or =80. RESULTS There were 140 patients randomized between 1986 and 1996, 71 to the implant arm and 69 to external irradiation only. Pathologically 125 patients had necrosis noted in their tumor specimen. Factors associated with improved survival in univariate analysis were age < or =50, KPS > or =90, chemotherapy at recurrence, and reoperation at the original tumor site. The Cox proportional hazards model revealed the following significant factors: treatment at recurrence (chemotherapy or reoperation) with a relative risk (RR) of 0.6 (p = 0.004) and KPS > or =90 with a RR 0.6 (p = 0.007). Randomization to the implant arm was associated with a RR of 0.7 (p = 0.07). Median survival for patients randomized to brachytherapy or not were 13.8 vs. 13.2 months, respectively, p = 0.49. CONCLUSIONS We conclude that stereotactic radiation implants have not demonstrated a statistically significant improvement in survival in the initial management of patients with malignant astrocytoma.

Radiotherapy for atypical or malignant intracranial meningioma

PURPOSE To study the natural history of intracranial atypical and malignant meningiomas, and the role of radiotherapy in the treatment of these tumors. METHODS AND MATERIALS The records of the 59 patients who were treated at the Princess Margaret Hospital between 1966 and 1990 with histologically confirmed intracranial atypical or malignant meningiomas were retrospectively reviewed. The median age was 58 years. Twenty-four patients were referred for radiation immediately after diagnosis and the remainder after at least one recurrence. The extent of the most recent surgery prior to radiation was gross total excision in 17, subtotal excision in 35, biopsy in 3, and none or unknown in 4. Seventeen had atypical meningiomas, defined as the presence of mitoses, nuclear atypia, or necrosis. Forty-two had malignant meningiomas on the basis of brain invasion (60%) or a pathologists designation of malignant or hemangiopericytic meningioma. All patients received megavoltage radiation to a median dose of 50 Gy. RESULTS Disease progressed in 39 patients (66%) after radiation. Of these, 36 died of meningioma and 3 were alive after further surgery. The 5-year actuarial overall and cause-specific survivals were 28 and 34%, respectively. Age less than 58, treatment after 1975, and a radiation dose of 50 Gy or more were independently associated with higher cause-specific survival by multivariate analysis. CONCLUSIONS Young age, modern imaging and treatment planning techniques, and a postoperative radiation dose of at least 50 Gy contribute to improved outcome in patients with atypical or malignant meningiomas. We recommend that all patients receive radiotherapy immediately after initial surgery.

Expanding global access to radiotherapy

Radiotherapy is a critical and inseparable component of comprehensive cancer treatment and care. For many of the most common cancers in low-income and middle-income countries, radiotherapy is essential for effective treatment. In high-income countries, radiotherapy is used in more than half of all cases of cancer to cure localised disease, palliate symptoms, and control disease in incurable cancers. Yet, in planning and building treatment capacity for cancer, radiotherapy is frequently the last resource to be considered. Consequently, worldwide access to radiotherapy is unacceptably low. We present a new body of evidence that quantifies the worldwide coverage of radiotherapy services by country. We show the shortfall in access to radiotherapy by country and globally for 2015-35 based on current and projected need, and show substantial health and economic benefits to investing in radiotherapy. The cost of scaling up radiotherapy in the nominal model in 2015-35 is US

ADJUVANT AND SALVAGE RADIATION THERAPY AFTER RADICAL PROSTATECTOMY FOR ADENOCARCINOMA OF THE PROSTATE

26·6 billion in low-income countries,

Gut Microbial Metabolism Drives Transformation of Msh2-Deficient Colon Epithelial Cells

62·6 billion in lower-middle-income countries, and

Inter- and Intrafractional Tumor and Organ Movement in Patients With Cervical Cancer Undergoing Radiotherapy: A Cinematic-MRI Point-of-Interest Study

94·8 billion in upper-middle-income countries, which amounts to

Tumour genomic and microenvironmental heterogeneity for integrated prediction of 5-year biochemical recurrence of prostate cancer: a retrospective cohort study

184·0 billion across all low-income and middle-income countries. In the efficiency model the costs were lower:

The relationship between elevated interstitial fluid pressure and blood flow in tumors : A bioengineering analysis

14·1 billion in low-income,

Magnetic resonance imaging (MRI) for localization of the prostatic apex: comparison to computed tomography (CT) and urethrography

33·3 billion in lower-middle-income, and