Evidence-based review of three-dimensional conformal radiotherapy for localized prostate cancer: an ASTRO outcomes initiative

PURPOSE: To perform a systematic review of the evidence to determine the efficacy and effectiveness of three-dimensional conformal radiotherapy (3D-CRT) for localized prostate cancer; provide a clear presentation of the key clinical outcome questions related to the use of 3D-CRT in the treatment of localized prostate cancer that may be answered by a formal literature review; and provide concise information on whether 3D-CRT improves the clinical outcomes in the treatment of localized prostate cancer compared with conventional RT. METHODS AND MATERIALS: We performed a systematic review of the literature through a structured process developed by the American Society for Therapeutic Radiology and Oncology's Outcomes Committee that involved the creation of a multidisciplinary task force, development of clinical outcome questions, a formal literature review and data abstraction, data review, and outside peer review. RESULTS: Seven key clinical questions were identified. The results and task force conclusions of the literature review for each question are reported. CONCLUSION: The technological goals of reducing morbidity with 3D-CRT have been achieved. Randomized trials and follow-up of completed trials remain necessary to address these clinical outcomes specifically with regard to patient subsets and the use of hormonal therapy.     

Selective mediastinal node irradiation based on FDG-PET scan data in patients with non-small-cell lung cancer: a prospective clinical study

PURPOSE: To evaluate the patterns of recurrence when selective mediastinal node irradiation based on FDG-PET scan data is used in patients with non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: A prospective Phase I/II study was undertaken on 44 patients with NSCLC without detectable distant metastases on CT and FDG-PET scan, delivering either 61.2 Gy in 34 fractions over 23 days or 64.8 Gy in 36 fractions over 24 days (1.8 Gy b.i.d. with 8-h interval). Only the primary tumor and the positive mediastinal areas on the pretreatment FDG-PET scan were irradiated. Isolated nodal failure was defined as recurrence in the regional nodes outside of the clinical target volume, in the absence of in-field failure. RESULTS: The CT and FDG-PET stage distribution was as follows: Stage I: 8 patients (18%) and 13 patients (29%); Stage II: 6 patients (14%) and 10 patients (23%); Stage IIIA: 15 patients (34%) and 7 patients (16%); Stage IIIB: 15 patients (34%) and 14 patients (32%), respectively. After a median follow-up time of 16 months (95% confidence interval [CI], 11-21 months) postradiotherapy, 11 patients (25%) developed a local recurrence. Only 1 patient (crude rate, 2.3%; upper bound of 95% CI, 10.3%), with a Stage II tumor on both CT and PET, developed an isolated nodal failure. The median actuarial overall survival was 21 months (95% CI, 14-28 months), and the median actuarial progression-free survival was 18 months (95% CI, 12-24 months). CONCLUSIONS: Selective mediastinal node irradiation based on FDG-PET scan data in patients with NSCLC results in low isolated nodal failure rates. In the Phase I component of this trial, radiation dose escalation up to 64.8 Gy in 36 fractions over 24 days is feasible.     

Fuchs' heterochromic cyclitis

Fuchs' heterochromic cyclitis (FHC) is a chronic anterior segment inflammatory syndrome that accounts for 2 to 3% of all uveitis cases. The etiology is unknown, but Herpes simplex, ocular toxoplasmosis and rubella infection have been implicated in the pathogenesis of the disease. It occurs more commonly in the third and fourth decades of life with an equal gender distribution. Patients are usually asymptomatic but may present with floaters and blurry vision. There is a mild but persistent anterior chamber reaction with diffuse and characteristic white stellate keratic precipitates. Iris and trabecular meshwork show abnormal vessels that may sometimes lead to a hyphema. Synechia formation is uncommon. Heterochromia is considered an important feature and accounts for the name, but it is variable depending on the intensity of the anterior stromal atrophy, initial iris color and amount of pigment in the iris pigmented epithelium. Progression of the disease is associated with cataract formation and glaucoma. Anti-inflammatory treatment is not indicated for the low-grade anterior chamber reaction seen in Fuchs' patients. Occasionally, a short course of corticosteroids is indicated if a symptomatic exacerbation occurs. The long-term prognosis is good, and patients usually maintain a visual acuity of 20/40 or better.     

Sustained complete remission of metastatic dermatofibrosarcoma protuberans with imatinib mesylate

Dermatofibrosarcoma protuberans (DFSP) is a soft tissue tumor which may recur locally and rarely causes metastases to vital organs. DFSPs have specific chromosomal abnormalities involving the platelet-derived growth factor beta-chain locus (PDGFB) which may render these tumors responsive to targeted therapy with the tyrosine kinase inhibitor imatinib mesylate. A patient with locally recurrent and metastatic DFSP resistant to first-line chemotherapy was treated with imatinib mesylate 400 mg/day. The tumor was examined by a novel fluorescence in situ hybridization (FISH) method for specific rearrangements of the PDGFB locus. The patient was followed for response and toxicity by physical examination and imaging studies. FISH revealed PDGFB rearrangement indicative of multiplication of the PDGFB fusion locus within a ring chromosome. Physical examination showed response within the first month of treatment, and subsequent computed tomography and fluorodeoxyglycose positron emission tomography documented complete response to imatinib therapy. Our patient is now in sustained complete remission for 20 months with minimal toxicity. We conclude that sustained complete remission of metastatic DFSP with specific FISH abnormalities involving the PDGFB locus can be obtained with imatinib mesylate with minimal toxicity for the patient.     

Prediction model for the incidence and prevalence of type 1 diabetes in childhood and adolescence: evidence for a cohort-dependent increase within the next two decades in Germany

Ehehalt S, Dietz K, Willasch AM, Neu A; for the DIARY‐Group Baden‐Wuerttemberg. Prediction model for the incidence and prevalence of type 1 diabetes in childhood and adolescence: evidence for a cohort‐dependent increase within the next two decades in Germany. Objective: To provide data on type 1 diabetes (T1D) epidemiology in childhood over a period of 20 years and to predict prevalence and cohort‐age‐specific incidence rates (IRs) for the next two decades in Germany. Methods: The Baden‐Wuerttemberg Diabetes Incidence Registry (DIARY) includes children and adolescents below 15 years of age with new onset of T1D (period 1987–2006, n = 5108 cases). Results: The mean age‐ and sex‐standardized IR was 15.3/100 000/year (95% CI 14.8–15.7) and the average increase in the IR was 4.4% per year (95% CI 3.9–4.9). Within the next 20 years (2007–2026), the risk for developing diabetes will increase like the square of a linear function with calendar year for all age ranges. There is a strong correlation between the predicted IRs of the cohorts and the observed IRs (n = 300; root mean square error = 0.56; r² = 0.71) and a negative correlation between mean age at onset and T1D IR (p = 0.02). On 31 December 2006, the prevalence of T1D was 0.126% (95% CI 0.121–0.132). The predicted prevalence (end of 2026) is estimated to be 0.265% (95% CI 0.25–0.28; predicted cases: n = 2950; 95% CI 2900–3000). Conclusions: In comparison to observations made in the past, the risk of disease rises even faster than expected: The younger the child, the quicker the increase of the cohort‐age‐specific IR and the higher the risk for T1D during lifetime.     

NLRP7 and the genetics of post-molar choriocarcinomas in Senegal

Gestational choriocarcinomas are malignant tumors of trophoblastic cells that affect 5-25% of women with sporadic hydatidiform moles (HMs) depending on countries and studies. Nucleotide binding and oligomerization domain-like receptor protein 7 (NLRP7) is a major gene responsible for recurrent HMs and recently mutations in this gene have also been shown in 13% of women with sporadic, non-recurrent moles. To investigate the role of NLRP7 in the genetic susceptibility for the malignant degeneration of moles, we sequenced its 11 exons in 43 Senegalese patients with post-molar choriocarcinomas. We report the presence of three novel NLRP7 variants that were found only in patients but not in 100 controls from the Senegalese general population, 100 controls from the Tunisian general population, and 100 controls from the Canadian population. In addition, this analysis revealed significant differences in the frequencies of four non-synonymous NLRP7 variants between European and Senegalese controls with the biggest difference being for variant G487E present at a minor allele frequency of 3.5% in Europeans, 18.1% in Tunisians and 45.6% in Senegalese. Comparing human NLRP7 and its paralog, NLRP2, with their mammalian counterparts revealed that allele E at position 487 is most likely the ancestral allele that was acquired in Africa but driven to low frequencies in Europeans and Asians due to migration, population bottlenecks and selective pressures. This study is the first attempt to investigate the role of NLRP7 in choriocarcinomas and highlights the higher frequencies of NLRP7 variants in the general Senegalese and Tunisian populations both known to have higher frequencies of moles and choriocarcinomas.