Low dose rate brachytherapy (LDR-BT) as monotherapy for early stage prostate cancer in Italy: practice and outcome analysis in a series of 2237 patients from 11 institutions.

OBJECTIVE: Low-dose-rate brachytherapy (LDR-BT) in localized prostate cancer is available since 15 years in Italy. We realized the first national multicentre and multidisciplinary data collection to evaluate LDR-BT practice, given as monotherapy, and outcome in terms of biochemical failure. METHODS: Between May 1998 and December 2011, 2237 patients with early-stage prostate cancer from 11 Italian community and academic hospitals were treated with iodine-125 ((125)I) or palladium-103 LDR-BT as monotherapy and followed up for at least 2 years. (125)I seeds were implanted in 97.7% of the patients: the mean dose received by 90% of target volume was 145 Gy; the mean target volume receiving 100% of prescribed dose (V100) was 91.1%. Biochemical failure-free survival (BFFS), disease-specific survival (DSS) and overall survival (OS) were estimated using Kaplan-Meier method. Log-rank test and multivariable Cox regression were used to evaluate the relationship of covariates with outcomes. RESULTS: Median follow-up time was 65 months. 5- and 7-year DSS, OS and BFFS were 99 and 98%, 94 and 89%, and 92 and 88%, respectively. At multivariate analysis, the National Comprehensive Cancer Network score (p < 0.0001) and V100 (p = 0.09) were correlated with BFFS, with V100 effect significantly different between patients at low risk and those at intermediate/high risk (p = 0.04). Short follow-up and lack of toxicity data represent the main limitations for a global evaluation of LDR-BT. CONCLUSION: This first multicentre Italian report confirms LDR-BT as an excellent curative modality for low-/intermediate-risk prostate cancer. ADVANCES IN KNOWLEDGE: Multidisciplinary teams may help to select adequately patients to be treated with brachytherapy, with a direct impact on the implant quality and, possibly, on outcome.

Clinical radiobiology of glioblastoma multiforme: estimation of tumor control probability from various radiotherapy fractionation schemes.

BACKGROUND AND PURPOSE: The aim of this study was to estimate a radiobiological set of parameters from the available clinical data on glioblastoma (GB). PATIENTS AND METHODS: A number of clinical trial outcomes from patients affected by GB and treated with surgery and adjuvant radiochemotherapy were analyzed to estimate a set of radiobiological parameters for a tumor control probability (TCP) model. The analytical/graphical method employed to fit the clinical data allowed us to estimate the intrinsic tumor radiosensitivity (α), repair capability (b), and repopulation doubling time (T d ) in a first phase, and subsequently the number of clonogens (N) and kick-off time for accelerated proliferation (T(k)). The results were used to formulate a hypothesis for a schedule expected to significantly improve local control. The 95 % confidence intervals (CI(95 %)) of all parameters are also discussed. RESULTS: The pooled analysis employed to estimate the parameters summarizes the data of 559 patients, while the studies selected to verify the results summarize data of 104 patients. The best estimates and the CI(95 %) are α = 0.12 Gy⁻¹ (0.10-0.14), b = 0.015 Gy⁻² (0.013-0.020), α/b = 8 Gy (5.0-10.8), T(d) = 15.4 days (13.2-19.5), N = 1.104(1.2.10³ - 1.105), and T(k) = 37 days (29-46). The dose required to offset the repopulation occurring after 1 day (D(prolif)) and starting after T k was estimated as 0.30 Gy/day (0.22-0.39). CONCLUSION: The analysis confirms a high value for the α/b ratio. Moreover, a high intrinsic radiosensitivity together with a long kick-off time for accelerated repopulation and moderate repopulation kinetics were found. The results indicate a substantial independence of the duration of the overall treatment and an improvement in the treatment effectiveness by increasing the total dose without increasing the dose fraction.

Head and neck intensity modulated radiotherapy parotid glands: time of re-planning.

PURPOSE: To investigate the correct time point for re-planning by evaluating dosimetric changes in the parotid glands (PGs) during intensity-modulated radiotherapy (IMRT) in head and neck cancer patients. MATERIALS AND METHODS: Patients with head and neck cancer treated with IMRT were enrolled. During treatment all patients underwent cone-beam computed tomography (CBCT) scans to verify the set-up. CBCT scans at treatment days 10, 15, 20 and 25 were used to transfer the original plan (CBCTplan I, II, III, IV, respectively) using rigid registration between the two. The PGs were retrospectively contoured and evaluated with the dose-volume histogram. The mean dose, the dose to 50 % of volume, and the percentage of volume receiving 30 and 50 Gy were evaluated for each PG. The Wilcoxon sign ranked test was used to evaluate the effects of dosimetric variations and values <0.05 were taken to be significant. RESULTS: From February to June 2011, ten patients were enrolled and five IMRT plans were evaluated for each patient. All the dosimetric parameters increased throughout the treatment course. However, this increase was statistically significant at treatment days 10 and 15 (CBCTplan I, II; p = 0.02, p = 0.03, respectively). CONCLUSION: CBCT is a feasible method to assess the dosimetric changes in the PGs. Our data showed that checking the PG volume and dose could be indicated during the third week of treatment.

Is ExacTrac x-ray system an alternative to CBCT for positioning patients with head and neck cancers?

PURPOSE: To evaluate the usefulness of a six-degrees-of freedom (6D) correction using ExacTrac robotics system in patients with head-and-neck (HN) cancer receiving radiation therapy. METHODS: Local setup accuracy was analyzed for 12 patients undergoing intensity-modulated radiation therapy (IMRT). Patient position was imaged daily upon two different protocols, cone-beam computed tomography (CBCT), and ExacTrac (ET) images correction. Setup data from either approach were compared in terms of both residual errors after correction and punctual displacement of selected regions of interest (Mandible, C2, and C6 vertebral bodies). RESULTS: On average, both protocols achieved reasonably low residual errors after initial correction. The observed differences in shift vectors between the two protocols showed that CBCT tends to weight more C2 and C6 at the expense of the mandible, while ET tends to average more differences among the different ROIs. CONCLUSIONS: CBCT, even without 6D correction capabilities, seems preferable to ET for better consistent alignment and the capability to see soft tissues. Therefore, in our experience, CBCT represents a benchmark for positioning head and neck cancer patients.

Impact of comorbidity in elderly prostate cancer patients treated with brachytherapy.

OBJECTIVE: To analyze the correlations among comorbidity and overall survival (OS), biochemical progression-free survival (b-PFS) and toxicity in elderly patients with localized prostate cancer treated with (125)I brachytherapy. METHODS: Elderly men, aged ≥65 years, with low-intermediate risk prostate cancer, were treated with permanent (125)I brachytherapy as monotherapy. Comorbidity data were obtained from medical reports using age-adjusted Charlson comorbidity index (a-CCI). The patients were categorized into two age groups (<75 and ≥75 years old), and two comorbidity score groups (a-CCI ≤3 and >3). Toxicity was scored with Radiation Therapy Oncology Group (RTOG) scale. RESULTS: From June 2003 to October 2009, a total of 92 elderly patients underwent prostate brachytherapy, including 57 men (62%) with low-risk prostate cancer, and 35 men (38%) with intermediate-risk prostate cancer. The median age of patients was 75 years (range, 65-87 years). Forty-seven patients (51%) had a-CCI ≤3 and 45 patients (49%) a-CCI >3. With a median follow-up period of 56 months (range, 24-103 months), the 5-year actuarial OS and b-PFS were 91.3% and 92.4% respectively, without statistical significance between two Charlson score groups. Toxicity was mild. None of the patients experienced gastrointestinal (GI) toxicity, and only 4 patiens (4%) experienced late genitourinary (GU) grade-3 (G3) toxicity. No correlation between acute GU and GI toxicity and comorbidity was showed (P=0.50 and P=0.70, respectively). CONCLUSIONS: Our data suggest that elderly men with low-intermediate risk prostate cancer and comorbidity can be considered for a radical treatment as (125)I low-dose rate brachytherapy.

Monitor unit optimization in RapidArc plans for prostate cancer.

Intensity-modulated radiation therapy (IMRT) has become a standard treatment for prostate cancer based on the superior sparing of the bladder, rectum, and other surrounding normal tissues compared to three-dimensional conformal radiotherapy, despite the longer delivery time and the increased number of monitor units (MU). The novel RapidArc technique represents a further step forward because of the lower number of MUs per fraction and the shorter delivery time, compared to IMRT. This paper refers to MU optimization in RA plans for prostate cancer, using a tool incorporated in Varian TPS Eclipse. The goal was to get the lowest MU RA plan for each patient, keeping a well-defined level of PTV coverage and OAR sparing. Seven prostate RA plans (RA MU-Optimized) were retrospectively generated using the MU optimization tool in Varian Eclipse TPS. Dosimetric outcome and nontarget tissue sparing were, compared to those of RA clinical plans (RA Clinical) used to treat patients. Compared to RA Clinical, RA MU-Optimized plans resulted in an about 28% (p = 0.018) reduction in MU. The total integral dose (ID) to each nontarget tissue (but not the penile bulb) showed a consistent average relative reduction, statistically significant only for the femoral heads. Within the intermediate dose region (40-60 Gy), ID reductions (4%-17% p < 0.05) were found for the rectum, while a slight but significant (0.4%-0.9%, p < 0.05) higher ID was found for the whole body. Among the remaining data, the mean dose to the bladder was also reduced (-12%, p = 0.028). Plans using MU optimization are clinically applicable and more MU efficient, ameliorating the exposure of the rectum and the bladder to intermediate doses.

Local tumor control probability to evaluate an applicator-guided volumetric-modulated arc therapy solution as alternative of 3D brachytherapy for the treatment of the vaginal vault in patients affected by gynecological cancer.

The purpose of this study was to evaluate the applicator-guided volumetric-modulated arc therapy (AGVMAT) solution as an alternative to high-dose-rate brachytherapy (HDR-BRT) treatment of the vaginal vault in patients with gynecological cancer (GC). AGVMAT plans for 51 women were developed. The volumetric scans used for plans were obtained with an implanted CT-compatible vaginal cylinder which provides spatial registration and immobilization of the gynecologic organs. Dosimetric and radiobiological comparisons for planning target volume (PTV) and organs at risk (OARs) were performed by means of a dose-volume histogram (DVH), equivalent uniform dose (EUD), and local tumor control probability (LTCP). In addition, the integral dose and the overall delivery time, were evaluated. The HDR-BRT averages of EUD and minimum LTCP were significantly higher than those of AGVMAT. Doses for the OARs were comparable for the bladder and sigmoid, while, although HDR-BRT was able to better spare the bowel, AGVMAT provided a significant reduction of d2cc, d1cc, and dmax (p < 0.01) for the rectum. AGVMAT integral doses were higher than HDR-BRT with low values in both cases. Delivery times were about two or three times higher for HDR-BRT with respect to the single arc technique (AGVMAT1) and dual arc technique (AGVMAT2), respectively. The applicator-guided volumetric-modulated arc therapy seems to have the potential of improving rectum avoidance. However, brachytherapy improves performance in terms of PTV coverage, as demonstrated by a greater EUD and better LTCP curves.

Radiotherapy and bevacizumab for intramedullary and leptomenigeal metastatic glioblastoma: a case report and review of the literature.

Glioblastoma (GBM) developed metastases rarely and the prognosis, in these cases, was very poor. We reported a 30-year patient who, developing intramedullary and leptomeningeal metastases from GBM, underwent palliative spinal radiotherapy (RT) and Bevacizumab.

Comorbidity assessment and adjuvant radiochemotherapy in elderly affected by glioblastoma.

To assess the role of comorbidity on outcome in elderly patients with glioblastoma treated with radiotherapy plus concomitant and adjuvant Temozolomide, patients over 65 years with glioblastoma, who underwent surgical resection or biopsy and radiochemotherapy, were evaluated. The Adjusted-Age Charlson Comorbidity Index and the Adult Comorbidity Evaluation-27 were used to assess comorbidity. From April 2005 to January 2011, 35 patients (median age 72 years) were treated in our Institution. Thirteen patients had a Charlson score more than 3, while, according to the Adult Comorbidity Evaluation-27, 21 patients had mild or severe comorbid conditions. Patients with low Charlson comorbidity score experienced a longer survival time than those with higher score (22 vs. 10 months, respectively). The Adjusted-Age Charlson Comorbidity Index influenced survival at univariate and multivariate analysis (p = 0.004, p = 0.001, respectively). No comorbidity index was a predictor for progression-free survival. Our data suggested that the association of radiotherapy with TMZ was safe and effective. Perhaps, the comorbidity assessment could be an appropriate tool in the treatment decision for elderly patients with glioblastoma.

Ewing sarcoma of the thoracic wall in a 54-year-old man.

Ewing tumor is the second most common bone tumor in children. Its variant, malignant small cell tumor of the thoracopulmonary region, is infrequent in children and extremely rare in adults. A multimodal treatment approach is preferred for this tumor. We describe a rare case of primitive neuroectodermal tumor/Ewing sarcoma arising from the thoracic wall in a 54-year-old man. He underwent extensive resection of the tumor followed by adjuvant chemotherapy and radiotherapy.

A case of thyroid metastasis of nasopharyngeal cancer.

AIMS AND BACKGROUND: Thyroid metastasis from nasopharyngeal carcinoma is a rare occurrence. We report a case of thyroid metastases from nasopharyngeal carcinoma with a review of the literature. METHODS: In April 2007 a 59-year-old man was diagnosed with nasopharyngeal carcinoma; in October 2009 he underwent a thyroid biopsy that revealed G2 infiltrating spinocellular carcinoma with lymph node involvement. He was treated with chemotherapy and radiotherapy at our institute. RESULTS: Currently, after 6 cycles of adjuvant chemotherapy with taxotere and gemcitabine, the patient is asymptomatic with stable disease and improved quality of life. CONCLUSION: According to the literature, the treatment choice depends on clinical disease extent. Surgery and/or chemo-radiation therapy must therefore be tailored to the individual patient in order to improve clinical outcome and quality of life.

A retrospective analysis after low-dose-rate prostate brachytherapy with permanent (125)I seed implant: clinical and dosimetric results in 70 patients.

AIMS AND BACKGROUND: To evaluate the biochemical disease-free survival (bDFS) rate after (125)I permanent-implant prostate brachytherapy. METHODS: Patients with a diagnosis of prostate adenocarcinoma and adequate PSA follow-up were selected for this retrospective study. Brachytherapy with permanent (125)I seeds was performed as monotherapy, with a prescribed dose of 145 Gy to the prostate. Patients were stratified into recurrence risk groups according to the National Comprehensive Cancer Network (NCCN) guidelines. Biochemical failure was defined using the American Society of Therapeutic Radiology and Oncology (ASTRO) guidelines. The post-implant D90 (defined as the minimum dose covering 90% of the prostate) was obtained for each patient. Two cutoff points were used to test the correlation between D90 and bDFS results: 130 Gy and 140 Gy. bDFS was calculated from the implant date to the date of biochemical recurrence. Univariate and multivariate analysis were performed using the SPSS software and included clinical stage, pretreatment PSA, Gleason score (GS), androgen deprivation therapy, D90, and risk groups. In the univariate analysis we used a cutoff point of 5.89 ng/mL for PSA and 5 for GS. RESULTS: From June 2003 to April 2007, 70 patients were analyzed. The patients' distribution into recurrence risk groups was as follows: 39 patients (56%) in the low-risk group, 23 patients (33%) in the intermediate-risk group, and 8 patients (11%) in the high-risk group. At a median follow-up of 47 months (range, 19-70 months) bDFS was 88.4%, with a global actuarial 5-year bDFS of 86%. Disease-related factors including initial PSA level, GS and risk group were significant predictors of biochemical failure ( P = 0.01, P = 0.01, P = 0.006, respectively). In multivariate analysis, risk group (P = 0.005) and GS (P = 0.03) were statistically significant. CONCLUSION: Our data are in agreement with those in the literature and, despite the short follow-up, confirm the advantage of brachytherapy for patients at low and intermediate risk of recurrence.