A nearby long gamma-ray burst from a merger of compact objects.

Gamma-ray bursts (GRBs) are flashes of high-energy radiation arising from energetic cosmic explosions. Bursts of long (greater than two seconds) duration are produced by the core-collapse of massive stars1, and those of short (less than two seconds) duration by the merger of compact objects, such as two neutron stars2. A third class of events with hybrid high-energy properties was identified3, but never conclusively linked to a stellar progenitor. The lack of bright supernovae rules out typical core-collapse explosions4-6, but their distance scales prevent sensitive searches for direct signatures of a progenitor system. Only tentative evidence for a kilonova has been presented7,8. Here we report observations of the exceptionally bright GRB 211211A, which classify it as a hybrid event and constrain its distance scale to only 346 megaparsecs. Our measurements indicate that its lower-energy (from ultraviolet to near-infrared) counterpart is powered by a luminous (approximately 1042 erg per second) kilonova possibly formed in the ejecta of a compact object merger.

Erratum: Measurement of Preheat Due to Nonlocal Electron Transport in Warm Dense Matter [Phys. Rev. Lett. 120, 025002 (2018)].

This corrects the article DOI: 10.1103/PhysRevLett.120.025002.

Asymmetries in core-collapse supernovae from maps of radioactive 44Ti in Cassiopeia A.

Asymmetry is required by most numerical simulations of stellar core-collapse explosions, but the form it takes differs significantly among models. The spatial distribution of radioactive (44)Ti, synthesized in an exploding star near the boundary between material falling back onto the collapsing core and that ejected into the surrounding medium, directly probes the explosion asymmetries. Cassiopeia A is a young, nearby, core-collapse remnant from which (44)Ti emission has previously been detected but not imaged. Asymmetries in the explosion have been indirectly inferred from a high ratio of observed (44)Ti emission to estimated (56)Ni emission, from optical light echoes, and from jet-like features seen in the X-ray and optical ejecta. Here we report spatial maps and spectral properties of the (44)Ti in Cassiopeia A. This may explain the unexpected lack of correlation between the (44)Ti and iron X-ray emission, the latter being visible only in shock-heated material. The observed spatial distribution rules out symmetric explosions even with a high level of convective mixing, as well as highly asymmetric bipolar explosions resulting from a fast-rotating progenitor. Instead, these observations provide strong evidence for the development of low-mode convective instabilities in core-collapse supernovae.

Measurement of Preheat Due to Nonlocal Electron Transport in Warm Dense Matter.

This Letter presents a novel approach to study electron transport in warm dense matter. It also includes the first x-ray Thomson scattering (XRTS) measurement from low-density CH foams compressed by a strong laser-driven shock at the OMEGA laser facility. The XRTS measurement is combined with velocity interferometry (VISAR) and optical pyrometry (SOP) providing a robust measurement of thermodynamic conditions in the shock. Evidence of significant preheat contributing to elevated temperatures reaching 17.5-35 eV in shocked CH foam is measured by XRTS. These measurements are complemented by abnormally high shock velocities observed by VISAR and early emission seen by SOP. These results are compared to radiation hydrodynamics simulations that include first-principles treatment of nonlocal electron transport in warm dense matter with excellent agreement. Additional simulations confirm that the x-ray contribution to this preheat is negligible.

Embryonal tumors in Canadian children less than 36 months of age: results from the Canadian Pediatric Brain Tumor Consortium (CPBTC).

Embryonal tumors are a heterogeneous group of central nervous system (CNS) tumors whose subgroups have varying incidence and outcome. Despite these differences, they are often grouped as a single entity for study purposes. To date, there are no Canadian multi-institutional studies examining the incidence and outcome of all embryonal subtypes. The current study is an observational study reviewing embryonal tumors in all patients less than 36 months of age diagnosed with a CNS tumor in Canada from 1990 to 2005. Embryonal tumors accounted for 26.9% of all CNS tumors. Medulloblastomas were the highest proportion of the embryonal tumors at 61.5%. Atypical teratoid/rhabdoid tumors (AT/RT) had the second highest proportion of embryonal tumors at 18%. The proportion of primitive neuroectodermal tumors (PNET) was 16%, with 2.6 and 1.9% for congenital medulloepithelioma and ependymoblastoma tumors, respectively. AT/RT and PNET were more common in younger age groups. Medulloblastoma became more prevalent with increasing age, with its highest prevalence in the 25 to 36 month age group. Survival rates for our Canadian population at 18 and 24 months were 0.74 and 0.68 for medulloblastoma, 0.64 and 0.60 for PNET, and 0.36 and 0.29 for AT/RT, respectively. Overall, our data are comparable with published international rates for embryonal tumors. These incidence and outcome figures can guide future research into these rare tumors.

The unusual γ-ray burst GRB 101225A from a helium star/neutron star merger at redshift 0.33.

Long γ-ray bursts (GRBs) are the most dramatic examples of massive stellar deaths, often associated with supernovae. They release ultra-relativistic jets, which produce non-thermal emission through synchrotron radiation as they interact with the surrounding medium. Here we report observations of the unusual GRB 101225A. Its γ-ray emission was exceptionally long-lived and was followed by a bright X-ray transient with a hot thermal component and an unusual optical counterpart. During the first 10 days, the optical emission evolved as an expanding, cooling black body, after which an additional component, consistent with a faint supernova, emerged. We estimate its redshift to be z = 0.33 by fitting the spectral-energy distribution and light curve of the optical emission with a GRB-supernova template. Deep optical observations may have revealed a faint, unresolved host galaxy. Our proposed progenitor is a merger of a helium star with a neutron star that underwent a common envelope phase, expelling its hydrogen envelope. The resulting explosion created a GRB-like jet which became thermalized by interacting with the dense, previously ejected material, thus creating the observed black body, until finally the emission from the supernova dominated. An alternative explanation is a minor body falling onto a neutron star in the Galaxy.

Association between menthol-flavoured cigarette smoking and flavoured little cigar and cigarillo use among African-American, Hispanic, and white young and middle-aged adult smokers.

OBJECTIVES: Flavour additives in cigarettes and little cigars and cigarillos (LCCs), which influence smokers' risk perceptions, may reinforce dual flavoured tobacco use. We examined the association among mentholated cigarette use, risk perceptions for flavour additives in LCCs and flavoured LCC smoking behaviour. METHODS: Data from a national probability sample of 964 young and middle-aged adult current cigarette smokers were analysed. Multinomial logistic regression models examined the relationship among mentholated cigarette smoking, risk perceptions and current flavoured LCC use for the analytic sample and gender and race/ethnicity. RESULTS: Daily menthol cigarette smokers, compared to occasional, non-menthol smokers, had increased odds of flavoured LCC smoking (OR=1.75, 95% CI 1.02 to 2.98). This relationship was found for males, blacks/African-Americans and Hispanics/Latinos (p<0.05). Positive perceptions of menthol-flavoured additives in LCCs was associated with increased odds of flavoured LCC use among the analytic sample, males and blacks/African-Americans (p<0.05). Positive perceptions for clove-flavoured, spice-flavoured and alcohol-flavoured additives were also associated with flavoured LCC use among the analytic sample (p<0.05). CONCLUSIONS: Use of menthol-flavoured cigarettes and positive perceptions about menthol-flavoured and other flavour additives in LCCs may contribute to dual use with flavoured LCCs among adult cigarette smokers, specifically those from vulnerable populations.

Swift and NuSTAR observations of GW170817: Detection of a blue kilonova.

With the first direct detection of merging black holes in 2015, the era of gravitational wave (GW) astrophysics began. A complete picture of compact object mergers, however, requires the detection of an electromagnetic (EM) counterpart. We report ultraviolet (UV) and x-ray observations by Swift and the Nuclear Spectroscopic Telescope Array of the EM counterpart of the binary neutron star merger GW170817. The bright, rapidly fading UV emission indicates a high mass (≈0.03 solar masses) wind-driven outflow with moderate electron fraction (Ye ≈ 0.27). Combined with the x-ray limits, we favor an observer viewing angle of ≈30° away from the orbital rotation axis, which avoids both obscuration from the heaviest elements in the orbital plane and a direct view of any ultrarelativistic, highly collimated ejecta (a γ-ray burst afterglow).

Atomic physics modeling of transmission spectra of Sc-doped aerogel foams to support OMEGA experiments.

We present synthetic transmission spectra generated with PrismSPECT utilizing both the ATBASE model and the Los Alamos opacity library (OPLIB) to evaluate whether an alternative choice in atomic data will impact modeling of experimental data from radiation transport experiments using Sc-doped aerogel foams (ScSi6O12 at 75 mg/cm3 density). We have determined that in the 50-200 eV Te range there is a significant difference in the 1s-3p spectra, especially below 100 eV, and for Te = 200 eV above 5000 eV in photon energy. Examining synthetic spectra generated using OPLIB with 300 resolving power reveals spectral sensitivity to Te changes of ∼3 eV.

Characterization of activating mutations of NOTCH3 in T-cell acute lymphoblastic leukemia and anti-leukemic activity of NOTCH3 inhibitory antibodies.

Notch receptors have been implicated as oncogenic drivers in several cancers, the most notable example being NOTCH1 in T-cell acute lymphoblastic leukemia (T-ALL). To characterize the role of activated NOTCH3 in cancer, we generated an antibody that detects the neo-epitope created upon gamma-secretase cleavage of NOTCH3 to release its intracellular domain (ICD3), and sequenced the negative regulatory region (NRR) and PEST (proline, glutamate, serine, threonine) domain coding regions of NOTCH3 in a panel of cell lines. We also characterize NOTCH3 tumor-associated mutations that result in activation of signaling and report new inhibitory antibodies. We determined the structural basis for receptor inhibition by obtaining the first co-crystal structure of a NOTCH3 antibody with the NRR protein and defined two distinct epitopes for NRR antibodies. The antibodies exhibit potent anti-leukemic activity in cell lines and tumor xenografts harboring NOTCH3 activating mutations. Screening of primary T-ALL samples reveals that 2 of 40 tumors examined show active NOTCH3 signaling. We also identified evidence of NOTCH3 activation in 12 of 24 patient-derived orthotopic xenograft models, 2 of which exhibit activation of NOTCH3 without activation of NOTCH1. Our studies provide additional insights into NOTCH3 activation and offer a path forward for identification of cancers that are likely to respond to therapy with NOTCH3 selective inhibitory antibodies.

Alternative and complementary therapy use in pediatric oncology patients in British Columbia: prevalence and reasons for use and nonuse.

PURPOSE: Alternative and complementary therapies are infrequently studied in pediatric populations. We performed a population-based survey to aid health care workers in identifying and counseling parents who may use these remedies. PATIENTS AND METHODS: We retrospectively surveyed the parents of 583 pediatric patients diagnosed with cancer in British Columbia between 1989 and 1995. Prevalence and factors that influence the use and nonuse of alternative and complementary therapies were estimated. RESULTS: Alternative and complementary therapies were used by 42% of 366 respondents. Herbal teas, plant extracts, and therapeutic vitamins were the most commonly used alternative therapies. Relaxation/imagery strategies, massage, and therapeutic touch were the most commonly used complementary techniques. Factors that influenced the use of alternative/complementary therapies were prior use (chi2 = 60.0, P < .0001), prior positive attitude towards these remedies (chi2 = 41.6, P < .0001), soliciting information from family and friends (chi2 = 70.5, P < .0001) or from alternative care givers (chi2 = 58.7, P < .0001), high risk of death at diagnosis (chi2 = 9.6, P < .002), and advanced education of the father (chi2 = 7.4, P < .006) or mother (chi2 = 8.6, P < .003). Parents who used alternative/complementary therapies did so in conjunction with conventional medicine (98%). Lack of knowledge and fear of interference with conventional therapies were the most common reasons cited for nonuse. No parent believed that the quality of life of their child deteriorated due to the use of alternative/complementary therapies. CONCLUSION: Alternative and complementary therapy use in pediatric oncology patients is common. Factors have been identified that may be associated with undertaking their use.

The Third Intergroup Rhabdomyosarcoma Study.

PURPOSE: The ultimate goal of the Third Intergroup Rhabdomyosarcoma Study (IRS-III, 1984 to 1991) was to improve treatment outcome in children with rhabdomyosarcoma through clinical trials comparing risk-based protocols of surgery and multiagent chemotherapy, with or without irradiation. PATIENTS AND METHODS: One thousand sixty-two previously untreated, eligible patients who were entered onto the study after surgery were randomized or assigned to treatment by clinical group (I through IV), histology (unfavorable or favorable), and site of the primary tumor. Initial responses, progression-free survival (PFS), and survival (S) were the end points used in comparisons between randomized groups and between patients treated in IRS-III and IRS-II (1978 to 1984). RESULTS: The overall outcome of therapy in IRS-III was significantly better than in IRS-II (5-year PFS, 65% +/- 2% v 55% +/- 2%; P < .001 by stratified testing). Patients with group I favorable-histology tumors fared as well on a 1-year regimen of vincristine and dactinomycin (VA), as did a comparable group treated with VA plus cyclophosphamide (C) (5-year PFS, 83% +/- 3% v 76% +/- 4%; P = .18). Results for patients with group II favorable-histology tumors, excluding orbit, head, and paratesticular sites, were inconclusive regarding the benefit from addition of doxorubicin (ADR) to VA. Patients with group III tumors, excluding those in special pelvic, orbit, and other selected nonparameningeal head sites, fared much better on the more intensive regimens of IRS-III than on pulsed VAC or VAC-VADRC in IRS-II (5-year PFS estimates, 62% +/- 3% v 52% +/- 3%; P < .01); however, there were no significant differences in outcome among the groups treated in IRS-III. Patients with metastatic disease at diagnosis (clinical group IV) did not benefit significantly from the more complex therapies evaluated in IRS-III. CONCLUSION: Intensification of therapy for most patients in IRS-III, using a risk-based study design, significantly improved treatment outcome overall. The largest gain from this strategy was realized in patients with gross residual tumor after biopsy (clinical group III). It was also possible to decrease therapy for selected patient subsets without compromising survival.

MOPP or radiation in addition to ABVD in the treatment of pathologically staged advanced Hodgkin's disease in children: results of the Children's Cancer Group Phase III Trial.

PURPOSE: A randomized trial designed to compare mechlorethamine, vincristine, procarbazine, and prednisone (MOPP)/doxorubicin, bleomycin, vinblastine, and daccarbazine (ABVD) (regimen A) with ABVD plus low-dose regional (extended-field) radiation therapy (EF RT) (regimen B) for the treatment of children and adolescents with stages III and IV Hodgkin's disease was conducted by the Children's Cancer Group (CCG-521) from 1986 until 1990. PATIENTS AND METHODS: One hundred eleven eligible patients were randomized, 57 to regimen A and 54 to regimen B. All patients had pathologically verified stage III or stage IV Hodgkin's disease. RESULTS: Overall survival (S) is 87% at 4 years and event-free survival (EFS) is 82%. Patients randomized to ABVD plus EF RT have a 4-year EFS of 87% compared with 77% for patients randomized to MOPP/ABVD (P = .09, two-sided). Patients randomized to ABVD plus EF RT have a 4-year S of 90% compared with 84% for patients randomized to MOPP/ABVD (P = .45, two-sided). Significant prognostic factors in multivariate analysis for EFS are stage of disease, erythrocyte sedimentation rate (ESR) at diagnosis, liver size at diagnosis, and, among stage III patients, the size of the mediastinal mass at diagnosis. The acute toxicities of treatment are largely hematopoietic in nature, whereas acute pulmonary and cardiac toxicities are modest and not limiting. CONCLUSION: The results of this study show that, in advanced-stage Hodgkin's disease in children, equivalent results can be obtained by the addition of either MOPP or low-dose EF RT to the ABVD regimen; whether the addition of either contributes to outcome was not addressed in this study and will require additional testing. It is clear, however, that MOPP chemotherapy can safely be eliminated from front-line combination chemotherapy regimens for advanced Hodgkin's disease in pediatric patients.

Efficacy and toxicity of 12 courses of ABVD chemotherapy followed by low-dose regional radiation in advanced Hodgkin's disease in children: a report from the Children's Cancer Study Group.

Sixty-four patients aged 2 to 18 years with advanced-stage Hodgkin's disease (HD) were treated on a Children's Cancer Study Group (CCSG) pilot toxicity study (521-P). Therapy consisted of 12 courses of Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), bleomycin, vinblastine, and dacarbazine (ABVD), followed by low-dose (2,100 cGy in 12 fractions) regional irradiation (RT). All patients were monitored for toxicity with particular attention to the pulmonary system. Six patients (9%) developed grade 3 or 4 pulmonary toxicity. Three had grade 3 toxicity based solely on changes in carbon monoxide diffusing capacity (DLCO) and remained well for more than 3 years after diagnosis. There was one fatality among the three symptomatic cases. In five cases, toxicity occurred prior to RT. One occurred after seven courses of ABVD, one after nine courses, and three after 10 courses. In one of these five cases, ABVD was stopped. The patient was given nitrogen mustard (mechlorethamine), vincristine, prednisone, and procarbazine (MOPP). This patient subsequently developed recurrence of HD and died of overwhelming sepsis. The other four continued on study and completed their chemotherapy. Three patients had no further bleomycin, and one continued bleomycin at 50% of the assigned dose. They all received mantle RT following chemotherapy, one with a boost dose to the mediastinum to 3,800 cGy and one with added RT to both lungs (1,050 cGy). In the sixth case of pulmonary toxicity, symptoms were first noticed 2 weeks after mantle RT to 3,500 cGy. This patient died of progressive respiratory failure. The event-free survival (EFS) and overall survival is 87% at 3 years. These early results indicate that this therapy is effective in advanced HD in children but has a 9% incidence of acute pulmonary toxicity.

Intergroup rhabdomyosarcoma study-IV: results for patients with nonmetastatic disease.

PURPOSE: The study goal was to improve outcome in children with rhabdomyosarcoma by comparing risk-based regimens of surgery, radiotherapy (RT) and chemotherapy. PATIENTS AND METHODS: Eight hundred eighty-three previously untreated eligible patients with nonmetastatic rhabdomyosarcoma entered the Intergroup Rhabdomyosarcoma Study-IV (IRS-IV) (1991 to 1997) after surgery and were randomized treatment by primary tumor site, group (1 to 3), and stage (I to III). Failure-free survival (FFS) rates and survival were the end points used in comparisons between randomized groups and between patient subgroups treated on IRS-III and IRS-IV. Most patients were randomized to receive vincristine and dactinomycin (VA) and cyclophosphamide (VAC, n = 235), or VA and ifosfamide (VAI, n = 222), or vincristine, ifosfamide, and etoposide (VIE, n = 236). Patients with group 3 tumors were randomized to receive conventional RT (C-RT) versus hyperfractionated RT (HF-RT). RESULTS: Overall 3-year FFS and survival were 77% and 86%, respectively. Three-year FFS rates with VAC, VAI, and VIE were 75%, 77%, and 77%, respectively (P =.42). No significant difference in outcome was noted with HF-RT versus C-RT (P =.85 and P =.90, respectively). Overall, patients with embryonal tumors benefited from intensive three-drug chemotherapy in IRS-IV (3-year FFS, 83%). The improvement was seen for patients with stage I or stage II/III, group 1/2 disease, many of whom received VA chemotherapy on IRS-III. Patients with stage 2/3, group 3 disease had similar outcomes on IRS-III and IRS-IV. Three-year FFS for the nonrandomized patient subsets was 75% with renal abnormalities; 81% for paratesticular, group 1 cases; and 91% for group 1/2 orbit or eyelid tumors. Patients with paratesticular primaries had poorer outcomes if they were more than 10 years old (3-year FFS, 63% v 90%). Myelosuppression occurred in most patients, but toxic deaths occurred in less than 1%. CONCLUSION: VAC and VAI or VIE with surgery (with or without RT), are equally effective for patients with local or regional rhabdomyosarcoma and are more effective for embryonal tumors than therapies used previously. Younger patients with group 1 paratesticular embryonal tumors and all patients with group 1/2 orbit or eyelid tumors can usually be cured with VA chemotherapy along with postoperative RT for group 2 disease.

Chromatin modulation of glucocorticoid and progesterone receptor activity.

Steroid hormone receptors are ligand-activated transcription factors that enhance or repress gene expression. They act by binding to target sites within the promoters of genes assembled as chromatin. Chromatin structure is modified in response to steroid hormones and represents a critical step in steroid receptor signaling. Recent experiments demonstrate that the progesterone and glucocorticoid receptors are differentially influenced by this arrangement of DNA and histones. One of the most important developments in the steroid hormone receptor field has been the identification of coactivators and cointegrators, some of which are histone acetyltransferases. These proteins appear to play an important role in mediating ligand activation of transcription, although their exact role on chromatin templates is undefined.

Supernovae. 44Ti gamma-ray emission lines from SN1987A reveal an asymmetric explosion.

In core-collapse supernovae, titanium-44 ((44)Ti) is produced in the innermost ejecta, in the layer of material directly on top of the newly formed compact object. As such, it provides a direct probe of the supernova engine. Observations of supernova 1987A (SN1987A) have resolved the 67.87- and 78.32-kilo-electron volt emission lines from decay of (44)Ti produced in the supernova explosion. These lines are narrow and redshifted with a Doppler velocity of ~700 kilometers per second, direct evidence of large-scale asymmetry in the explosion.

Hyperfractionated radiation in children with rhabdomyosarcoma--results of an Intergroup Rhabdomyosarcoma Pilot Study.

PURPOSE: The Intergroup Rhabdomyosarcoma Study (IRS) Group initiated a pilot study (IRS IV-P) of hyperfractionated radiation (HF XRT) with chemotherapy to test the feasibility and toxicity of this combined modality approach in children with localized but nonresected (group III) and metastatic (group IV) rhabdomyosarcoma. METHODS AND MATERIALS: Using the linear quadratic equation, and an alpha/beta ratio of 10 Gy for acute reacting tumor effect and 3 Gy for late reacting normal tissue effect, a HF XRT protocol was developed giving a total radiation dose of 59.4 Gy, in 1.10 Gy fractions, twice daily at 6-8 h intervals. All patients received chemotherapy in addition to irradiation. The radiation scheme was calculated to increase the biologically effective dose to the tumor by 10% without increasing late effects, when compared to a conventional schedule of 50.4 Gy in 1.8 Gy daily fractions. This protocol also was predicted to cause an increase in acute normal tissue effects. RESULTS: Four hundred forty-nine children age 21 years and younger were eligible for the hyperfractionated radiation study of whom 297 had Group III disease and 152 had Group IV disease. A total of 117 patients were excluded from the feasibility and toxicity analysis because of progressive disease or death prior to scheduled irradiation, surgical resection, major protocol violation, treatment with brachytherapy, or missing data. Thus, 332 children were evaluable for the HF XRT protocol. Twenty-eight of the 332 (8%) were given conventional radiation because of physician preference or young age. Twenty of the 332 (6%) were not irradiated because of young age, anesthesia, or transportation problems. All nonirradiated children were < or = 3 years of age. Thus, 284 children, 86% of the evaluable population, received HF XRT. The radiation dose, number of fractions, number of days, and interfractional interval were scored as appropriate in 93% of cases. Review of radiation portals revealed that in 230 of 284 cases (81%) the radiation fields were appropriate, as per protocol. Thus, the HF XRT was feasible treatment in a multiinstitutional study. Analysis of toxicity revealed that 152 of 204 (75%) of Group III and 52 of 80 (65%) of Group IV patients experienced severe or life-threatening toxicity, explained by the addition of chemotherapy with the radiation. The majority of this toxicity was hematopoietic. Observed organ toxicity, which was potentially explained by the radiation treatment, was greatest at the end of radiation, and improved at the 6-week and 3-month evaluation periods. There were no deaths attributed to radiation toxicity and no instance of toxicity that required alteration of the radiation protocol. Thus, the treatment was not associated with toxicity that was considered excessive or unusual. CONCLUSION: The IRS IV-P study confirms that HF XRT combined with chemotherapy is both feasible and tolerable in children with rhabdomyosarcoma. A prospective randomized trial is underway to test its efficacy as compared to conventional radiation among children also receiving concurrent chemotherapy for rhabdomyosarcoma.

Radiation therapy for rhabdomyosarcoma: local failure risk for Clinical Group III patients on Intergroup Rhabdomyosarcoma Study II.

PURPOSE: A subset of 362 pediatric patients with rhabdomyosarcoma was selected from a total of 532 eligible IRS-II patients in Clinical Group III to assess the local and regional failure rates following radiotherapy and to determine patient, tumor, and treatment factors contributing to the risk for local and regional failure. METHODS AND MATERIALS: The study population was selected from all eligible IRS-II Clinical Group III patients. Excluded patients were those with "special pelvic" primary sites whose protocol management restricted radiotherapy (n = 123), and those who were removed from the study before radiotherapy was to begin, or because it was omitted (n = 47). A binary recursive partitioning model was used to identify subgroups of the remaining 362 patients at risk of local or regional failure. RESULTS: The local (only) failure rate was 17% (95% confidence interval, 13-21%), and the local (all) failure rate was 20% (95% confidence interval, 16-24%). The 5-year actuarial risk of local (all) failure was 22% (95% confidence interval, 18-27%). The risk of regional (nodal) failure was between 2% and 23%. Increasing tumor size predicted an increased local failure risk. Primary tumors located above the clavicle had a reduced risk of local failure. The binary recursive partitioning model identified a subset of patients at high risk of local failure. Those patients had primary tumors in the chest, pelvic region, extremity, or trunk, or tumors > 10 cm in diameter. Their local failure rate was 35% (compared to 15% for the remaining patients). The subset of patients at high risk for regional (nodal) failure had node involvement at diagnosis and a primary tumor originating at a site other than orbit, parameningeal, or trunk. Compliance with radiation treatment guidelines approached but did not achieve statistical significance as a predictive factor for local failure. By univariate analysis, factors not influencing local failure risk were age, race, gender, adenopathy, and histology. CONCLUSION: Radiation therapy and chemotherapy administered to Clinical Group III patients entered into the IRS-II protocol produced sustained local control in most cases. Knowledge of the factors which predict an increased risk of local or regional failure will facilitate the design of new treatment strategies.

Pion conformal radiation of prostate cancer: results of a randomized study.

PURPOSE: To compare the efficacy of pion radiation therapy with conventional external beam photon therapy, for the treatment of locally advanced stage T3/4, N0, M0 adenocarcinoma of the prostate. METHODS AND MATERIALS: Two hundred seventeen eligible patients were randomly allocated to either photon or pion therapy. No adjuvant hormone therapy was used. RESULTS: Median follow-up was 42 months (range 2-90). Acute bladder toxicity was worse in the pion arm, p = 0.2, but other acute toxicity did not differ. Late grade 2 toxicity was significantly less in the pion arm (29% at 5 years versus 48%, p = 0.002), but late grade 3 or 4 toxicity did not differ. Clinical local control was not significantly different between treatment arms (64% after 5 years with photons, 56% with pions, p = 0.6). Cause-specific and overall survival also did not differ (p = 0.7). There was a significant delay in time to first failure in the photon arm, largely as a result of decreased biochemical relapse, p = 0.01. A multivariate analysis is presented. CONCLUSION: Pion therapy was well tolerated, with increased acute toxicity and significantly decreased late tissue injury. This contrasts with the late toxicity observed with higher LET particle therapy such as neutron therapy. No improvement in local control with pion therapy was observed.