Slit-like hypertensive hydrocephalus: Report of a late, complex, and multifactorial complication in an oncologic patient.

BACKGROUND: Several sophisticated techniques and many chemotherapy drugs have improved life expectancy of oncologic patients allowing us to observe late complications which present many years after the initial treatment. CASE DESCRIPTION: We present a unique case of a patient affected by acute lymphoblastic leukemia at the age of 6 years, treated with whole brain radiotherapy and intrathecal chemotherapy, developing meningiomatosis and leptomeningeal alterations as late complications and the interaction of these two entities caused a peculiar form of hydrocephalus without ventricular dilation. The diagnosis of pseudotumor cerebri was excluded due the postradio/chemotherapy development of meningiomatosis, not present in a previously head magnetic resonance imaging, that exerted compression to the Sylvian aqueduct causing intracranial hypertension with papillary stasis without ventricles enlargement due to brain stiffness. Moreover, a peculiar intraoperative rubbery consistency of brain parenchyma was detected strengthening this complex diagnosis. CONCLUSION: At the best of our knowledge, this is the first report of obstructive hydrocephalus without ventricles dilation caused by brain stiffness related to late alterations of oncologic treatments. This report could be a guide for further complex patients diagnoses and for improving treatments efficacy.

Clinical implication in the use of the AAA algorithm versus the AXB in nasopharyngeal carcinomas by comparison of TCP and NTCP values.

PURPOSE: Retrospective analysis of volumetric modulated arc therapy treatment plans to investigate qualitative, possible, clinical consequences of the use of AAA versus AXB in nasopharyngeal cancer (NPC) cases. METHODS: The dose distribution of 26 treatment plans, produced using RapidArc technique and AAA algorithm, were recalculated using AXB and the same number of monitor units provided by AAA and clinically delivered to each patient. The potential clinical effect of dosimetric differences in the planning target volume (PTV) and in organs at risk (OAR) were evaluated by comparing TCP and NTCP values. The Wilcoxon Signed Rank test was used for statistical comparison of all results obtained from the use of the two algorithms. RESULTS: The poorer coverage of the PTV, with higher prescribed dose, was reflected in the TCP, which was significantly lower when AXB was used, the median value was 81.55% (range: 74.90, 88.60%) and 84.10% (range: 77.70, 89.90%) for AAA (p < 0.001). OAR mean dose was lower in the AXB recalculated plan than the AAA plan and the difference was statistically significant for all the structures. The NTCP for developing mandible necrosis showed the largest median percentage difference between AAA and AXB (56.6%), the NTCP of risk for larynx edema of Grade ≥ 2 followed with 12.2%. CONCLUSIONS: Differences in dose distribution of NPC treatment plans recalculated with AXB are of clinical significance in those situations where the PTV and OAR involve air or bone, media in which AXB has been shown to more accurately represent the true dose distribution. The availability of AXB algorithm could improve patient dose estimation, increasing the data consistency of clinical trials.

Early radiation-induced changes evaluated by intravoxel incoherent motion in the major salivary glands.

PURPOSE: To investigate the potential of intravoxel incoherent motion (IVIM) MRI for early evaluation of irradiated major salivary glands. MATERIALS AND METHODS: Thirty-four patients with head-neck cancer were included in a prospective study. All patients underwent three serial IVIM-MRI: before, half-way through, and at the end of radiotherapy (RT). Apparent diffusion coefficient (ADC), ADClow derived in the low b-value range, perfusion fraction f, and pure diffusion coefficient D were estimated. Pretreatment values and early changes of diffusion parameters were correlated with parotid mean dose (Dmean ) and volume reduction after RT. RESULTS: Changes in diffusion parameters over time were all significant (P < 0.001 for ADC, ADClow , and D, P = 0.003 for f). Variations of ADC, ADClow , and f were not correlated with Dmean (P = 0.089, P = 0.252 and P = 0.884, respectively), whereas a significant relationship was found between changes in D and Dmean (r = 0.197 with CI95% = 0.004-0.375, P = 0.046). Pretreatment f and Dmean were the best independent predictors for the percentage shrinkage (P = 0.0003 and 0.0597 respectively; R(2) = 0.391). CONCLUSION: Early changes of irradiated major salivary glands can be noninvasively evaluated by IVIM-MRI. Perfusion-related coefficients in conjunction with dosimetric information increase our capability to predict the change in parotid volume and hence, if further validated, guide treatment strategy in RT.

Emerging biological treatments for uterine cervical carcinoma.

Cervical cancer is the third most common cancer worldwide, and the development of new diagnosis, prognostic, and treatment strategies is a major interest for public health. Cisplatin, in combination with external beam irradiation for locally advanced disease, or as monotherapy for recurrent/metastatic disease, has been the cornerstone of treatment for more than two decades. Other investigated cytotoxic therapies include paclitaxel, ifosfamide and topotecan, as single agents or in combination, revealing unsatisfactory results. In recent years, much effort has been made towards evaluating new drugs and developing innovative therapies to treat cervical cancer. Among the most investigated molecular targets are epidermal growth factor receptor and vascular endothelial growth factor (VEGF) signaling pathways, both playing a critical role in cervical cancer development. Studies with bevacizumab or VEGF receptor tyrosine kinase have given encouraging results in terms of clinical efficacy, without adding significant toxicity. A great number of other molecular agents targeting critical pathways in cervical malignant transformation are being evaluated in preclinical and clinical trials, reporting preliminary promising data. In the current review, we discuss novel therapeutic strategies which are being investigated for the treatment of advanced cervical cancer.

The role of radiotherapy in bladder cancer.

In this article we report on the current role of radiotherapy in the management of non-muscle invasive as well as in muscle invasive bladder cancer.
Radiotherapy seems to have no role in non-muscle invasive bladder cancer.
In muscle invasive bladder tumors, the role of radiotherapy is under investigation in view of new radiotherapy techniques and novel cytotoxic and biological agents.

Early perfusion changes in patients with recurrent high-grade brain tumor treated with Bevacizumab: preliminary results by a quantitative evaluation.

BACKGROUND: To determine whether early monitoring of the effects of bevacizumab in patients with recurrent high-grade gliomas, by a Perfusion Computed Tomography (PCT), may be a predictor of the response to treatment assessed through conventional MRI follow-up. METHODS: Sixteen patients were enrolled in the present study. For each patient, two PCT examinations, before and after the first dose of bevacizumab, were acquired. Areas of abnormal Cerebral Blood Volume (CBV) were manually defined on the CBV maps, using co-registered T1- weighted images, acquired before treatment, as a guide to the tumor location. Different perfusion metrics were derived from the histogram analysis of the normalized CBV (nCBV) maps; both hyper and hypo-perfused sub-volumes were quantified in the lesion, including tumor necrosis. A two-tailed Wilcoxon test was used to establish the significance of changes in the different perfusion metrics, observed at baseline and during treatment. The relationships between changes in perfusion and morphological MRI modifications at first follow-up were investigated. RESULTS: Significant reductions in mean and median nCBV were detected throughout the entire patient population, after only a single dose of bevacizumab. The nCBV histogram modifications indicated the normalization effect of bevacizumab on the tumor abnormal vasculature. An improvement in hypoxia after a single dose of bevacizumab was predictive of a greater reduction in T1-weighted contrast-enhanced volumes at first follow-up. CONCLUSIONS: These preliminary results show that a quantification of changes in necrotic intra-tumoral regions could be proposed as a potential imaging biomarker of tumor response to anti-VEGF therapies.

Influence of intensity-modulated radiation therapy technique on xerostomia and related quality of life in patients treated with intensity-modulated radiation therapy for nasopharyngeal cancer.

BACKGROUND: The purpose of this study was to compare 5-field and 7-field intensity-modulated radiation therapy (IMRT) techniques in terms of xerostomia and related quality of life in patients with nasopharyngeal cancer. METHODS: Eight and 23 patients were treated with 5-field (group I) and 7-field (group II) techniques, respectively. The xerostomia was evaluated using the Radiation Therapy Oncology Group (RTOG) scale, stimulated and unstimulated salivary flow (SSF/USF), and xerostomia-related questionnaires (XQs). The assessments were done before and at 3, 6, 12, 18, and 24 months after radiotherapy. RESULTS: The mean parotid dose was 45.7 Gy and 29.9 Gy and the ≥G3 toxicity at 24 months was 25% and 19% in group I and II, respectively. Sixty-three percent and 93% of patients recovered at least 25% of SSF pretherapy values. The XQ scores of both groups improved over time but more so in group II. CONCLUSION: The 7-field technique decreases the mean parotid dose, reducing xerostomia assessed by the RTOG/XQ score.

A novel dose constraint to reduce xerostomia in head-and-neck cancer patients treated with intensity-modulated radiotherapy.

PURPOSE: To investigate the predictors of incidence and duration of xerostomia (XT) based on parotid glands (PG), submandibular glands (SMG), and both glands taken as a whole organ (TG) in head-and-neck cancer patients treated with intensity-modulated radiotherapy. METHODS AND MATERIALS: A prospective study was initiated in May 2003. Sixty-three head-and-neck patients (44 with nasopharynx cancer) were included in the analysis. Using the dose-volume histogram the PG, SMG, and TG mean doses were calculated. Unstimulated and stimulated salivary flow were measured and XT-related questionnaires were compiled before and at 3, 6, 12, 18, and 24 months after radiotherapy. Salivary gland toxicity was evaluated using the Radiation Therapy Oncology Group scale, and Grade >or=3 toxicity was used as the endpoint. The XT incidence was investigated according to descriptive statistics and univariate and multivariate analysis. The Bonferroni method was used for multiple comparison adjustment. RESULTS: After a reduced flow at 3 months after radiotherapy, recovery of salivary flow was observed over time. Primary site and salivary gland mean doses and volumes were identified in univariate analysis as prognostic factors. Multivariate analysis confirmed that TG mean dose (p = 0.00066) and pretreatment stimulated salivary flow (p = 0.00420) are independent factors for predicting XT. CONCLUSION: The TG mean dose correlates with XT as assessed by Radiation Therapy Oncology Group criteria, salivary output, and XT-related questionnaires. Our results suggest that TG mean dose is a candidate dose constraint for reducing XT, requiring considerably more validation in non-nasopharyngeal cancer patients.

Analysis of salivary flow and dose-volume modeling of complication incidence in patients with head-and-neck cancer receiving intensity-modulated radiotherapy.

PURPOSE: To investigate dose-volume effects of salivary flow and the functional recovery over time, using salivary function data and different models of normal tissue complication probability (NTCP). METHODS AND MATERIALS: A total of 59 patients with head-and-neck cancer treated with intensity-modulated radiotherapy (IMRT) were analyzed in the present study. The toxicity was evaluated using the Radiation Therapy Oncology Group (RTOG) scale and salivary flows, both unstimulated (USF) and stimulated (SSF). The assessments were done before radiotherapy (RT) and at 3, 6, 12, 18, and 24 months after RT. Grade 3 toxicity was the primary endpoint. Analyses of toxicity incidence at 3, 6, and 12 months after RT were performed by both the Lyman-Kutcher-Burman (LKB) and relative seriality (S) models. RESULTS: A significant correlation was found between the incidence of Grade 3 toxicity and the incidence of patients with a reduction in SSF to <25% of the pre-RT value. Better correlations resulted between the RTOG toxicity score and the dosimetric parameters, compared with USF/SSF. The TD(50), assessed by the LKB model, was 21.4, 27.8, and 41.6 Gy at 3, 6, and 12 months after RT, respectively. The TD(50), assessed by the S model, was 20.0, 26.3, and 40.0 Gy at 3, 6, and 12 months after RT, respectively. CONCLUSION: Recovery of salivary gland function vs. time after RT took place mostly within 1 year after RT. The RTOG Grade 3 was a reliable score to perform the NTCP modeling. The choice of NTCP model had no influence on the accuracy of predictions.

Accelerated hyperfractionated radiotherapy and concurrent protracted venous infusion chemotherapy in locally advanced head and neck cancer.

Concurrent radiotherapy and chemotherapy result in a significant benefit with respect to induction chemotherapy followed by radiotherapy or radiotherapy alone, although with a significant increase of toxicity. To discover a more tolerated and effective chemoradiation regimen, the feasibility and efficacy of a hyperfractionated accelerated irradiation with concurrent protracted venous infusion chemotherapy was investigated. Sixty-five patients with advanced head and neck cancer underwent a definitive (53 patients) or a postoperative adjuvant (12 patients) chemoradiation treatment. Chemotherapy consisted of an intravenous protracted infusion of 5 and 200 mg/m /d cisplatin and 5-fluorouracil, respectively. Radiotherapy consisted of a split-course accelerated hyperfractionation of two 150-cGy (split twice a day) or three 100-cGy fractions per day (split three times a day) at more than 6-hour intervals, for 2 weeks followed, after a 1-week interruption, by 2-to-3-week treatment, with the same fractionation schedule, to a total dose of 60 Gy to 69 Gy. Confluent mucositis was tolerable and was the cause of treatment delay of more than 10 days in only 20% of patients. Grade 3 or greater systemic toxicity occurred only in 9 of 65 (14%) patients and was never the cause of drug dose reduction. Complete responses were observed in 69% of patients with gross diseases. At a median follow-up of 43.5 months, 45% of patients were alive and free of disease and 38% died of cancer. The 5-year actuarial local regional failure was 35%. The 5-year actuarial disease-specific survival was 50%. Preservation of larynx function was achieved in 47% of living patients and in 74% of all patients, with advanced tumors of the laryngopharynx. The long-term results of this study suggest that this chemoradiation regimen has the potential of achieving a significant improvement over standard therapy while avoiding significant toxicity.