Registered Replication Report: Rand, Greene, and Nowak (2012).

In an anonymous 4-person economic game, participants contributed more money to a common project (i.e., cooperated) when required to decide quickly than when forced to delay their decision (Rand, Greene & Nowak, 2012), a pattern consistent with the social heuristics hypothesis proposed by Rand and colleagues. The results of studies using time pressure have been mixed, with some replication attempts observing similar patterns (e.g., Rand et al., 2014) and others observing null effects (e.g., Tinghög et al., 2013; Verkoeijen & Bouwmeester, 2014). This Registered Replication Report (RRR) assessed the size and variability of the effect of time pressure on cooperative decisions by combining 21 separate, preregistered replications of the critical conditions from Study 7 of the original article (Rand et al., 2012). The primary planned analysis used data from all participants who were randomly assigned to conditions and who met the protocol inclusion criteria (an intent-to-treat approach that included the 65.9% of participants in the time-pressure condition and 7.5% in the forced-delay condition who did not adhere to the time constraints), and we observed a difference in contributions of -0.37 percentage points compared with an 8.6 percentage point difference calculated from the original data. Analyzing the data as the original article did, including data only for participants who complied with the time constraints, the RRR observed a 10.37 percentage point difference in contributions compared with a 15.31 percentage point difference in the original study. In combination, the results of the intent-to-treat analysis and the compliant-only analysis are consistent with the presence of selection biases and the absence of a causal effect of time pressure on cooperation.

Evidence for distinct populations of human Merkel cells.

Merkel cells (MCs) are neuroendocrine cells of unknown origin located in the skin. They are identified at electron microscopic level by electron dense granules, at light microscopic level by the presence of cytokeratins 8, 18, 19 and 20. Contradictory reports concerning the presence of other molecules of epithelial as well as neural origin prompted us to investigate whether there are distinct populations of human MCs. Here, we show the heterogeneous expression of villin, N-CAM, NGF-R, and neurofilaments in MCs. Synaptophysin is found in all MCs but with different intensity, nestin is absent. Expression patterns vary between interfollicular epidermis, hair follicles and glabrous epidermis. We conclude that there are distinct populations of MCs, but all populations contain markers for epithelial as well as neural cells. Putative functions of the distinct populations are discussed.

An ex-vivo oral mucosa infection model for the evaluation of the topical activity of antifungal agents.

Although Nystatin has been used since 1950s as a non-absorbable antifungal agent, there is still no reliable in-vivo data available stating a dose-effect relationship of Nystatin-suspension in the treatment of oropharyngeal infection with Candida albicans. Here, we studied the efficacy of a commercially available topical Nystatin suspension in a new ex-vivo model of candidiasis using porcine oral mucosa. After 48 and 96 h of C. albicans infection, 230 IU Nystatin (standard dosage), 100 IU and 20 IU proved to be equally efficacious. Multiple applications of Nystatin were not superior compared with single application. In dosages of 10 and 0.1 IU the activity of Nystatin suspension against C. albicans was no longer confirmed. In an agar diffusion model, the minimal biocidal concentration of Nystatin proved to be 0.25 IU. Our results suggest that the proposed porcine ex-vivo model is much closer to the in-vivo situation compared with other established in-vitro models of the treatment of muco-cutaneous candidiasis and may provide a substitute for animal models in the investigation of antifungal agents. Additionally, it seems to be a valuable tool for further investigations of the pathogenesis of C. albicans infections.

Tight junction proteins in the skin.

It has long been accepted that tight junctions (TJ) are crucial for the formation and maintenance of the paracellular barrier and for cell polarity in simple epithelia and endothelia. Moreover, it is long known that they play a role in barrier function of amphibian skin. However, only in recent years were TJ and TJ proteins identified in the epidermis of men and mice. Their involvement in the barrier function of mammalian skin has been shown. This review summarizes our current knowledge about TJ and TJ proteins in mammalian skin.

Telomerase activity of Merkel cell carcinomas and Merkel cell carcinoma-derived cell cultures.

Merkel cell carcinomas are rare malignant tumors of the skin, which are predominantly observed in elderly patients (mean age 65-70 years). It is believed but not yet proven that these tumors are derived from the Merkel cells of the epidermis and hair follicles. The Merkel cells themselves probably originate from an asymmetric cell division of basal keratinocytes and the resulting differentiated Merkel cells have presumably, at least in humans, lost their growth potential. The capability of indefinite cell division in germ line cells and in the great majority of malignant tumors as well as an increased growth potential in certain somatic cells (such as basal cells of renewable tissues) is correlated with cellular telomerase activity, which is absent in differentiated somatic cells. In this study the telomerase activity in cryostat sections of frozen Merkel cell tumor biopsies and in in vitro cultivated Merkel cell carcinoma cells was analyzed. We detected telomerase activity in four tumors and three of four cell cultures. These results show that despite their pronounced neuroendocrine differentiation and their occurrence in patients of advanced age, Merkel cell carcinomas possess telomerase activity similar to that of common carcinoma types.

Diversity of desmosomal proteins in regenerating epidermis: immunohistochemical study using a human skin organ culture model.

We recently established a skin organ culture model for epithelial healing by creating a central defect in freshly excised human skin specimens and keeping them in culture for up to 7 days, either untreated or with transplantation of allogenic or autologous keratinocytes. In this study the molecular diversity of cell-cell junction proteins in the regenerating epidermis was analysed immunohistochemically using a broad spectrum of monoclonal antibodies against glycoproteins (cadherins) and plaque proteins of desmosomes. At all stages studied the entire set of desmosomal cadherins [desmogleins (Dsg) 1-3 and desmocollins (Dsc) 1-3] was detected, with Dsg3, Dsc2 and Dsc3 being the most prominent. In the disordered neoepithelium at day 3 (after transplantation) some desmosomal cadherins appeared in their respective stratum compartments. In regenerating epidermis on day 7, which exhibited a more ordered stratification and a compact horny layer, stratification-related patterns of desmosomal cadherins were more pronounced. However, some immaturity of the day-7 neoepidermis was reflected by relatively low levels of the maturation-associated Dsgl and Dsc1 and a strong basal layer expression of Dsg2 which is sparse in normal epidermis. Desmosomal plaque proteins showed expression patterns similar to those in normal healthy epidermis. The adherens junction-related E-cadherin was also detected. Dendritic cells (melanocytes, Langerhans cells) were mainly present at the wound margins. In conclusion, this study demonstrated partial but not complete epidermal maturation and junction development during regeneration up to day 7. This model should also be useful in future studies to evaluate the effects of growth hormones to be used in therapeutic trials on chronic leg ulcers.

Characterization of epidermal wound healing in a human skin organ culture model: acceleration by transplanted keratinocytes.

Few data are available on early regeneration of human epidermis in vivo. We have established a supravital skin organ culture model for epidermal wound healing by setting a central defect (3 mm diameter) in freshly excised skin specimens and culturing under air exposure. Re-epithelialization was followed for up to 7 d by histology and immunohistologic analysis of various markers for differentiation and proliferation. In 12 of 19 cases (63%; 5% fetal calf serum) or six of 21 cases (29%; 2% fetal calf serum), the wounds were re-epithelialized spontaneously after 7 d. After transplantation to the wounds of 1-2 x 10(6) dissociated allogenic cultured epidermal or about 1 x 10(6) autologous outer root sheath keratinocytes, 18 of 21 cases (86%; 5% fetal calf serum) or 17 of 21 cases (81%; 2% fetal calf serum) were healed within the same period. Histologically, early neoepithelium (3 d) was disordered after keratinocyte transplantation, whereas later (7 d) it had gained a more ordered stratification, exhibiting a thin discontinuous granular and a compact horny layer. At this stage, not only hyperproliferative (CK 6) but also, abundantly, maturation-associated cytokeratins (CK 1, CK 10) were detected immunohistochemically. Analyses of regenerated epidermis after transplantation of (i) keratinocytes labeled in vitro with BrdU and (ii) heterosexual keratinocytes by immunohistochemistry and fluorescence in situ hybridization for the Y chromosome, respectively, clearly showed that external keratinocytes are physically integrated into the regenerated epidermis and extendedly contribute to its formation. The data presented here demonstrate improvement and acceleration of epidermal re-epithelialization by transplantation of keratinocytes.

Management of stage I-B, II-A, and II-B carcinoma of the cervix with high-dose-rate brachytherapy: initial results of an institutional clinical trial.

In 1989, the University of Miami began a program incorporating high-dose-rate (HDR) brachytherapy into the definitive treatment of patients with invasive carcinoma of the cervix. Patients received an average total dose to point A of 5,511 cGy (range 4,280-6,360 cGy) in an average of 57 days (range 39-84 days). An analysis of the first 24 cases found 11 FIGO Stage I-B, four Stage II-A, and nine Stage II-B tumors. At the end of all radiation therapy, 19/24 patients' tumors (79.2%) had undergone a clinical complete response (CR). With median follow-up of 26 months (range 14-63 months), three have relapsed locally, two regionally, and six in extrapelvic sites. Almost two-thirds of all failures occurred in patients with tumors >4 cm, who also took more than 8 weeks to complete their treatment. Overall 2-year actuarial survival for the entire study group is approximately 74%. A univariate analysis determined that clinical stage (P = 0.02), overall treatment time (P = 0.03), tumor size (P = 0.05), and response at the end of therapy (P = 0.005) were significant prognostic factors. Multivariate analysis showed that tumor response to therapy was the most important prognosticator of outcome (P = 0.001). Besides five cases of apical vaginal stenosis, there have been no reported chronic complications in this cohort of patients. A prospectively randomized trial is recommended to compare the efficacy of HDR vs. low-dose-rate brachytherapy in cervical carcinoma.

Radioresistance in murine solid tumors induced by interleukin-1.

Interleukin-1 (IL-1) has radioprotective activity in hematopoietic lineages and in other normal cell renewal systems, but little is known about the effects of IL-1 alpha on the radiosensitivity of tumor cell populations. The present studies were conducted to investigate the effects of IL-1 alpha on the radiosensitivity of clonogenic cells in RIF-1 and SCC-7 tumors. Radioresistance was detected within 2-4 after administration of IL-1 alpha (0.5 micrograms/mouse, ip) and characterized by increases in D(o), Dq, alpha/beta and SF2. This radioresistance was similar to that seen in tumors rendered totally hypoxic before X irradiation. Tirapazamine, a hypoxic cell cytotoxin, and IL-1 alpha had synergistic schedule-dependent antitumor activity in vivo, suggesting that IL-1-induced radioresistance in vivo is due to hypoxia. Radioresistance induced by IL-1 alpha was transient, and the data suggested reoxygenation within 12 h. In vitro, IL-1 alpha had no direct effect on the radiosensitivity of SCC-7 cells in tissue culture under aerobic conditions. However, an increase in D(o), alpha/beta and SF2 was seen in clonogenic tumor cells from primary cultures treated with IL-1 alpha under aerobic conditions. Superoxide dismutase and catalase prevented the induction of radioresistance by IL-1 alpha in vitro, suggesting that oxidative responses from tumor macrophages after administration of IL-1 alpha may be responsible for induced radioresistance by IL-1 in vitro. Although oxidant stress induced by IL-1 and in vitro in our models, the mechanisms by which such responses modulate tumor radiosensitivity in vivo and in vitro are likely quite different.

Scattered radiation from linear accelerator and cobalt-60 collimator jaws.

PURPOSE: Solid state diodes and/or thermoluminescent dosimeters (TLDs) are often used to measure scattered radiation doses to critical organs immediately adjacent to radiation field sites. The energy-dependent response of these commonly used in vivo dosimeters sometimes makes the interpretation of measured values uncertain. This study investigates scattered radiation arising from the collimator jaws of linear accelerators and the treatment head of a cobalt-60 teletherapy unit. METHODS AND MATERIALS: A thin window Markus-type parallel-plate ionization chamber placed in a polystyrene phantom was employed to document the magnitude, energy composition, and sources of scattered radiation at surfaces near radiation fields. Measurements were taken both with and without additional phantom material covering the ionization chamber, as well as with various distances between the ionization chamber and edges of the radiation fields tested. RESULTS: Data was collected, analyzed and compared for treatment units produced by different manufacturers. It was found that the magnitude of scattered radiation to surfaces immediately adjacent to radiation fields ranged from 1% to 15% of the maximum dose along the beam central axis. These values showed a strong dependence upon distance from the edge of the radiation field, beam energy, collimator setting (field size), and the presence of externally mounted accessories. Teletherapy unit differences due to manufacturing firm origins were found to only slightly affect scattered radiation magnitude, while the orientation of upper and lower collimator jaws had absolutely no effect. CONCLUSIONS: Percent depth dose curves of scattered radiation were obtained and analyzed. The shapes of these depth dose curves suggest the presence of complex energy spectra from secondary electrons and scattered x-rays. Because of the presence of these complex energy spectra in areas immediately adjacent to radiation fields, caution should be observed when interpreting patient doses near radiation fields, if dose values have been measured in vivo using thermoluminescent dosimeters (TLDs) or solid state diodes. Many of these on-patient dosimetry devices are strongly energy dependent and may demonstrate large over- or under-responses in areas dominated by scattered radiation. The results of this study, thus, suggest that ionization chambers are preferred for determination of scattered radiation doses in such regions.

The role of steroids in the management of metastatic carcinoma to the brain. A pilot prospective trial.

This prospective study attempted to evaluate the indications for glucocorticoids which are commonly given to patients with brain metastases. Twelve patients with histologically confirmed malignancies and radiographically documented brain metastases were enrolled. Patients were scored for general performance status and neurologic function class. All subjects were given high-dose dexamethasone (HDD) for 48 hours and then randomized to receive either intermediate-dose dexamethasone (IDD) or no steroids with cranial radiotherapy. Of these 12 study patients, 3 achieved a complete response, 1 partial response, and 8 nonresponses to HDD. Seven patients had IDD, while five received no IDD. Although a small sample size prevented any statistical analysis, this study does suggest that the place for using glucocorticoids in treating patients with metastatic carcinoma to the brain remains uncertain and should be evaluated in a cooperative prospective trial.

Long-term follow-up of gliomas treated with fractionated stereotactic irradiation.

Eighteen patients have been treated for gliomas with fractionated stereotactic linear accelerator (LINAC) irradiation. A plastic halo ring secured with skull pins allows daily attachment of the patient to the stereotactic frame mounted on the linear accelerator. The patients received 9-31 fractions of 1.8-3 Gy/fraction over periods of 20-49 days. Total doses delivered stereotactically where 16-60 Gy (90% isodose) delivered to 3-7 cm diameter tumors. The six patients with glioblastoma had a median survival of 16 months (range 7-60 months). The two patients with anaplastic astrocytoma survived 7 and 78 months. Most of the patients with high grade tumors also received other adjuant treatments. Of the ten patients with low grade gliomas, one expired 66 months after treatment, and the remainder are alive 22-82 months after treatment. One pediatric patient displayed evidence of focal radiation injury with visual loss. No patient developed initial recurrence of tumor outside the focally irradiated field. Stereotactic localization of irradiation protects surrounding brain tissue; fractionation improves the therapeutic ratio. These extended follow-up data indicate that stereotactic restriction of radiation fields in treatment of gliomas does not result in deterioration of survival results. Further investigation is warranted into the use of higher focal fractionated radiation doses to attempt to improve local control and survival.

A multivariate analysis of clinicopathologic factors for predicting outcome in uterine sarcomas.

This study involved a comprehensive review of the histologic slides of 62 patients who were diagnosed with uterine sarcoma from 1978 through 1988 at a single institution. In addition, DNA content (ploidy level) could be determined from the H & E slides of these tumors using image analysis. Also, 42 of these cases had retrievable cell blocks on which DNA analysis was performed by means of flow cytometry. A linear regression analysis found a high degree of correlation (r = 0.8) between the measurement of the DNA index of these tumors by these two techniques. All cases were retrospectively restaged using the newly adopted FIGO surgical staging criteria which found the following distribution: 22 (35.5%) Stage I, 10 (16.1%) Stage II, 12 (19.4%) Stage III, and 18 (29%) Stage IV. A multivariate analysis of 60 evaluable patients using the Cox proportional hazard model found that surgical staging was the most significant prognostic factor with respect to the endpoint of overall survival (P = 0.00004). Both patient age at diagnosis and mitotic index were independent from surgical staging in predicting outcome. Furthermore, there was a trend suggesting that DNA index also had prognostic value. Of particular interest was that patients with diploid tumors (DNA index, 0.9-1.1) had a 5-year overall survival of 72% and did not approach median survival; however, hyperdiploid tumors (DNA index > 1.1) and hypodiploid tumors (DNA index < 0.9) were associated with median survivals of 18 and 12 months, respectively. In conclusion, this study supports the use of surgical staging of patients with uterine sarcomas in order to optimally determine their chance for survival. Further biologic investigations which may result in identifying those patients who could benefit from adjunctive treatment are recommended.

Dose rate effect of 125I irradiation on normal rabbit eyes and experimental choroidal melanoma.

The dose rate effect of radiation by 125I plaque on choroidal melanoma and normal intraocular tissue was studied. In the first part of the experiment, high activity plaques (HAP) and low activity plaques (LAP) were implanted on rabbit eyes with experimental Greene choroidal melanoma to deliver a total dose of 10,000 cGy to the tumor apex. The mean dose rate calculated at 0.5 mm from the inner sclera in eight eyes with high activity plaques was 3341.5 cGy hr-1 (1 cGy = 1 rad) while that in ten eyes with low activity plaques was 239.9 cGy hr-1. For tumors less than 1.0 mm in height, both groups showed complete tumor regression at the tumor implantation site after plaque treatment. For tumors more than 1.0 mm in height, two out of two eyes in the low activity plaque group and one of four eyes in the high activity plaque group failed to show complete tumor regression. Both LAP and HAP were effective in eradicating tumors, but logistic regression analysis demonstrates that HAP was more effective than LAP when adjustment was made for initial tumor height (P = 0.032). Nine tumor control eyes without 125I plaque implantation demonstrated marked tumor growth within 3 weeks. In the second part of the experiment, 125I plaques were implanted on the sclera of 12 normal rabbits' eyes. Six received high dose rate plaque treatment, while the other six received low dose rate plaque treatment. Clinical and histologic examinations demonstrated more damaging effects to the normal chorioretinal tissues at the plaque implantation site in the high dose rate plaque group at 24 weeks of follow-up. These results suggest that high dose rate plaques are more effective than low dose rate plaques when tumor height is statistically controlled. However, high dose rate delivery increases the damaging effects on normal intraocular tissue.

Synergistic antitumor activity of cisplatin and interleukin 1 in sensitive and resistant solid tumors.

The antitumor activity of cis-diamminedichloroplatinum(II) (cP) and human recombinant interleukin-1 alpha (IL-1 alpha) was studied in RIF-1 and SC VII solid tumor models and in a cP-resistant subline of RIF-1 designated RIF-R1cP. In RIF-1 tumors, clonogenic cell survival after cP plus IL-1 alpha combinations was highly schedule and IL-1 alpha dose dependent. More than additive clonogenic cell kill was seen when cP was given 6 h before, but not 8 h before or at 2-6 h after IL-1 alpha. Time course studies indicated that maximal clonogenic cell killing was achieved within 4-6 h after the cP plus IL-1 alpha combination, with little or no recovery for up to 24 h. In vivo dose-response studies indicated that cP plus IL-1 alpha combinations induced more clonogenic cell kill than cP alone in all three tumor models, and analysis by the median effect principle indicated highly synergistic antitumor activity. Dexamethasone but not indomethacin inhibited the synergistic interaction. IL-1 alpha had no effect on the cytotoxicity of cP in SCC VII cells in vitro, and neither in vitro hypoxia nor in vivo ischemia, induced by clamping tumor blood supply, significantly affected cP clonogenic cell killing. Increased clonogenic cell killing was seen, however, after removal of the clamp, implicating reperfusion events, such as oxyradical stress, as a potential mechanism for increased cP cytotoxicity in SCC VII solid tumors. The data from our model systems provide a rationale for additional work to define the mechanisms of the synergistic antitumor activity of the cP plus IL-1 alpha combination and indicate that IL-1 alpha might be a useful adjunct to increase the clinical efficacy of cP-containing strategies for both sensitive and cP-resistant cancers.

A rapid method for electron beam energy check.

Assessment of electron beam energy and its long term stability is part of standard quality assurance practice in radiation oncology. Conventional depth-ionization or depth-film density measurements are time consuming both in terms of data acquisition and analysis. A procedure is described utilizing ionization measurements at two energy specific depths. It is based on a linear relationship between electron beam energy and its practical range. Energy shifts within the range covered by the two measurement depths are easily resolved. Within a range of +/- 0.50 MeV (+/- 1.30 MeV) around the established mean incident energy of 5.48 MeV (20.39 MeV), the method accuracy is better than 0.10 MeV.

Conservative surgery and radiation therapy for intraductal carcinoma of the breast.

Nineteen women with intraductal carcinoma of the breast were treated with conservative surgery and radiotherapy from 1982 to 1990. All underwent excisional biopsy or wide local excision of the primary tumor. Definitive irradiation consisted of 4500 cGy in 180 cGy fractions given through tangential fields followed by a breast boost to the primary site to a total dose of 5900-6500 cGy. No patient received regional node irradiation. Median follow-up was 38 months. The five year actuarial rate of local failure was 9%. One patient failed with an infiltrating ductal carcinoma in the treated breast 31 months after initial treatment. Salvage mastectomy was performed. She remains without evidence of disease 43 months after initial treatment. Metastatic breast carcinoma has not developed in any of the patients. Cosmetic result was good to excellent in all patients. With short-term follow-up, conservative surgery and radiotherapy appear to be an acceptable alternative to mastectomy in carefully selected patients with ductal carcinoma in situ. As retrospective and randomized trials mature, the natural history of these lesions treated with conservative surgery and irradiation will be further defined.

Tissue maximum ratios (and other parameters) of small circular 4, 6, 10, 15 and 24 MV x-ray beams for radiosurgery.

Small, circular, x-ray beams are commonly used for radiosurgery applications. Dosimetric characteristics of 4, 6, 10, 15 and 24 MV circular x-ray beams ranging in size from 10 to 40 mm are reported. These characteristics include the measurement of TMR, beam profiles and relative output factors. Measurements of these parameters were performed in a solid water phantom using film, a small diode, small parallel-plate and cylindrical ionization chambers and TLD. Comparison of relative dose measurements of small, circular beams performed using these detectors showed that the small diode, film and TLD results consistently agreed for circular beams as small as 10 mm diameter. Beam profiles were measured using film dosimetry. Comparison of TMR values of a 10 mm diameter beam measured using film and a small parallel-plate ionization chamber showed no significant differences. Tertiary collimators designed with tapered, divergence-matching holes, and straight-drilled holes have been used for radiosurgery applications. Measurement of beam penumbra produced with either of these types of tertiary collimators showed minimal differences between them.

Hyperfractionated radiation therapy and concurrent 5-fluorouracil, cisplatin and mitomycin-C in head and neck carcinoma. A pilot study.

Seventeen patients were entered into a Phase I/II trial of concurrent hyperfractionated radiation therapy (7,440 cGy total dose; 120 cGy b.i.d.) combined with constant infusion of 5-fluorouracil (5-FU) (1,000 mg/m2/24 hours for 72 hours) and cisplatin (DDP) (50 mg/m2) for a total of three cycles. Thirteen patients had Stage IV disease; three, Stage III disease; and one, Stage II hypopharyngeal disease. Thirteen of 17 patients had positive cervical lymph nodes, and the mean size of the largest lymph node was 5.5 x 5.1 cm. The patients were not treated with planned adjunctive surgery except for one patient who had a radical neck dissection for massive, rapidly growing cervical adenopathy, which recurred promptly within 1 month before the initiation of protocol therapy. After the initial six patients were entered, mitomycin-C (Mito 8 mg/m2) was added during the second cycle. All the patients completed the planned course of radiotherapy with a median dose of 7,440 cGy and a mean dose of 7,248 cGy except for two patients who died--one from toxicity and the other, suicide. The predominant toxicity was mucositis, which was grade 3/4 in 11 of 15 patients, resulting in an average interruption of radiation therapy of 12 days. Weight loss was significant and was on the average 12% of baseline weight. Hematological toxicity was mild in the 5-FU/DDP group (only one grade 3 toxicity of six) and severe in the 5-FU/DDP/Mito-treated patients (five of eight patients having grade 3/4 toxicity including one leukopenic pneumonitis death). Additional toxicity included one parapharyngeal cellulitis, which responded to antibiotics. Noncompliance with the complex regimen was only seen in three patients. One patient refused b.i.d. radiation therapy, and one patient refused further chemotherapy after the first cycle. Additionally, one patient who had a severe ethanol withdrawal reaction during the first cycle of 5-FU/DDP did not receive further chemotherapy. The complete response rate of both primary site and neck by the protocol regimen alone was 71%. However, two patients, one from each group, did undergo salvage neck dissection, and the locoregional control is currently 73%, with a mean follow-up time of 18.4 months. The feasibility of combining hyperfractionated radiation therapy with aggressive concurrent chemotherapy was demonstrated. The response and local control rate justifies the added toxicity of concurrent chemotherapy and radiation therapy.

Radiosurgery target point alignment errors detected with portal film verification.

Stereotactic radiosurgery with a linear accelerator requires an accurate match of the therapeutic radiation distribution to the localized target volume. Techniques for localization of the target volume using CT scans and/or angiograms have been described. Alignment of the therapeutic radiation distribution to the intended point in stereotactic space is usually accomplished using precision mechanical scales which attach to the head ring. The present work describes a technique used to verify that the stereotactic coordinates of the center of the intended radiation distribution are in agreement with the localized target point coordinates. This technique uses anterior/posterior and lateral accelerator portal verification films to localize the stereotactic coordinates of the center of the radiation distribution with the patient in the treatment position. The results of 26 cases have been analyzed. Alignment errors of the therapeutic radiation distribution in excess of 1 mm have been found using the portal film verification procedure.