Rothmund-Thomson syndrome (RTS; also known as poikiloderma congenitale) is a rare, autosomal recessive genetic disorder characterized by abnormalities in skin and skeleton, juvenile cataracts, premature ageing and a predisposition to neoplasia. Cytogenetic studies indicate that cells from affected patients show genomic instability often associated with chromosomal rearrangements causing an acquired somatic mosaicism. The gene(s) responsible for RTS remains unknown. The genes responsible for Werner and Bloom syndromes (WRN and BLM, respectively) have been identified as homologues of Escherichia coli RecQ, which encodes a DNA helicase that unwinds double-stranded DNA into single-stranded DNAs. Other eukaryotic homologues thus far identified are human RECQL, Saccharomyces cerevisiae SGS1 and Schizosaccharomyces pombe rqh1. We recently cloned two new human helicase genes, RECQL4 at 8q24.3 and RECQL5 at 17q25, which encode members of the RecQ helicase family. Here, we report that three RTS patients carried two types of compound heterozygous mutations in RECQL4. The fact that the mutated alleles were inherited from the parents in one affected family and were not found in ethnically matched controls suggests that mutation of RECQL4 at human chromosome 8q24.3 is responsible for at least some cases of RTS.

Merkel cell carcinoma (MCC) is a rare skin cancer that occurs more frequently after organ transplantation or B-cell malignancy, conditions of suppressed or disordered immunity. To assess further whether immune suppression increases MCC risk, we studied its occurrence in a cohort of 309365 individuals with acquired immunodeficiency syndrome (AIDS) by using linked AIDS and cancer registries. We identified six cases of MCC, corresponding to a relative risk of 13.4 (95% CI 4.9-29.1) compared with the general population. These results suggest that immune suppression induced by the human immunodeficiency virus increases MCC risk.

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Background. Cancers of individual organs generally are composed of various histologic types, each with its own frequency and demographic patterns. For childhood cancers in particular, a classification of cancers by histologic type is important for understanding the etiology and progression of the disease. Methods. Data from the Surveillance, Epidemiology, and End Results (SEER) Program on 9308 microscopically confirmed malignant neoplasms in children younger than age 15, newly diagnosed during 1973‐1987, were made available for analysis. Tumors were grouped histologically according to a classification previously utilized in an international volume of childhood cancer incidence. Results. The most frequent histologic types were acute lymphocytic leukemia (23.6%), astrocytoma (9.6%), neuroblastoma (6.6%), and Wilms' tumor (6.4%). Acute lymphocytic leukemia accounted for 75% of childhood leukemia. The most common form of Hodgkin's disease was the nodular sclerosing subtype, which was diagnosed in 56% of all cases. Burkitt's and Burkitt‐like disease accounted for approximately one third of non‐Hodgkin's lymphoma, the sex ratio (male to female) being unusually high (5.7). Among the brain tumors, glioma was of interest because 198 cases (excluded from this analysis) were diagnosed without histologic confirmation—due, no doubt, to their inaccessibility for biopsy because they were located in the brain stem. The most common histologic type of soft tissue sarcoma was rhabdomyosarcoma, which accounted for 51% of the total, more than half of which were of the embryonal type. To the authors' knowledge, this report offers for the first time the relative frequencies of rare types of leukemias, such as megakaryoblastic leukemia, in childhood. This report also includes the frequencies of 21 rarer forms of soft tissue sarcoma. Five forms of childhood cancer had a 5‐year relative survival rate of 85% or better. Of the cancers with the poorest outcome, three had relative survival rates of 46.5‐49%; the relative survival rate for acute myelogenous leukemia was only 26.4%. The trends in survival over time for 21 types of childhood cancer also are included in this report. Conclusions. Further refinements in classification now are available through laboratory techniques utilizing molecular biology, immunology, and cytogenetics, which are of importance in etiologic studies, diagnosis, treatment, and prognosis. It would be important in the future for cancer registries to record the results of relevant laboratory tests for further analysis by subtype.

Incidence and survival data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program for the 10-year period 1973-1982 are presented. Childhood cancer incidence rates have remained relatively stable over the last decade. The overall incidence rate increased slightly from 124 to 127 per million children from 1973-1977 to 1978-1982 while rates for leukemias remained unchanged over this same time period at 38 per million for all races combined. Leukemias and lymphomas accounted for 44% of all cancers among white children and 33% among blacks. For all forms of cancer combined, the 5-year relative survival rate was 57% for both whites and blacks. The 5-year relative survival rate exceeded 80% for fibrosarcomas, retinoblastomas, Hodgkin's disease, and gonadal and germ cell tumors. Survival rates for children have shown improvement during the last decade, the most dramatic improvements occurring among patients with leukemia (15% 5-year relative survival in 1967-1973 versus 51% in 1973-1981), non-Hodgkin's lymphoma (24% versus 51%), and bone tumors (28% versus 48%).

The 14 tumors reported in Rubinstein-Taybi syndrome since 1989, when added to the 22 previously reported, are beginning to show a pattern of neural and developmental tumors, especially of the head, which is malformed in the syndrome. Among the neoplasms were 12 of the nervous system: 2 each of oligodendroglioma, medulloblastoma, neuroblastoma, and benign meningioma, a pheochromocytoma, and 3 other benign tumors; 2 of nasopharyngeal rhabdomyosarcoma; and 1 each of leiomyosarcoma, seminoma, and embryonal carcinoma. Among the other benign tumors were an odontoma, a choristoma, a dermoid cyst, and 2 pilomatrixomas.

This paper reviews recent advances in 4D medical imaging (4DMI) and 4D radiation therapy (4DRT), which study, characterize, and minimize patient motion during the processes of imaging and radiotherapy. Patient motion is inevitably present in these processes, producing artifacts and uncertainties in target (lesion) identification, delineation, and localization. 4DMI includes time-resolved volumetric CT, MRI, PET, PET/CT, SPECT, and US imaging. To enhance the performance of these volumetric imaging techniques, parallel multi-detector array has been employed for acquiring image projections and the volumetric image reconstruction has been advanced from the 2D to the 3D tomography paradigm. The time information required for motion characterization in 4D imaging can be obtained either prospectively or retrospectively using respiratory gating or motion tracking techniques. The former acquires snapshot projections for reconstructing a motion-free image. The latter acquires image projections continuously with an associated timestamp indicating respiratory phases using external surrogates and sorts these projections into bins that represent different respiratory phases prior to reconstructing the cyclical series of 3D images. These methodologies generally work for all imaging modalities with variations in detailed implementation. In 4D CT imaging, both multi-slice CT (MSCT) and cone-beam CT (CBCT) are applicable in 4D imaging. In 4D MR imaging, parallel imaging with multi-coil-detectors has made 4D volumetric MRI possible. In 4D PET and SPECT, rigid and non-rigid motions can be corrected with aid of rigid and deformable registration, respectively, without suffering from low statistics due to signal binning. In 4D PET/CT and SPECT/CT, a single set of 4D images can be utilized for motion-free image creation, intrinsic registration, and attenuation correction. In 4D US, volumetric ultrasonography can be employed to monitor fetal heart beating with relatively high temporal resolution. 4DRT aims to track and compensate for target motion during radiation treatment, minimizing normal tissue injury, especially critical structures adjacent to the target, and/or maximizing radiation dose to the target. 4DRT requires 4DMI, 4D radiation treatment planning (4D RTP), and 4D radiation treatment delivery (4D RTD). Many concepts in 4DRT are borrowed, adapted and extended from existing image-guided radiation therapy (IGRT) and adaptive radiation therapy (ART). The advantage of 4DRT is its promise of sparing additional normal tissue by synchronizing the radiation beam with the moving target in real-time. 4DRT can be implemented differently depending upon how the time information is incorporated and utilized. In an ideal situation, the motion adaptive approach guided by 4D imaging should be applied to both RTP and RTD. However, until new automatic planning and motion feedback tools are developed for 4DRT, clinical implementation of ideal 4DRT will meet with limited success. However, simplified forms of 4DRT have been implemented with minor mo...

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