A giant planet candidate transiting a white dwarf.

Astronomers have discovered thousands of planets outside the Solar System1, most of which orbit stars that will eventually evolve into red giants and then into white dwarfs. During the red giant phase, any close-orbiting planets will be engulfed by the star2, but more distant planets can survive this phase and remain in orbit around the white dwarf3,4. Some white dwarfs show evidence for rocky material floating in their atmospheres5, in warm debris disks6-9 or orbiting very closely10-12, which has been interpreted as the debris of rocky planets that were scattered inwards and tidally disrupted13. Recently, the discovery of a gaseous debris disk with a composition similar to that of ice giant planets14 demonstrated that massive planets might also find their way into tight orbits around white dwarfs, but it is unclear whether these planets can survive the journey. So far, no intact planets have been detected in close orbits around white dwarfs. Here we report the observation of a giant planet candidate transiting the white dwarf WD 1856+534 (TIC 267574918) every 1.4 days. We observed and modelled the periodic dimming of the white dwarf caused by the planet candidate passing in front of the star in its orbit. The planet candidate is roughly the same size as Jupiter and is no more than 14 times as massive (with 95 per cent confidence). Other cases of white dwarfs with close brown dwarf or stellar companions are explained as the consequence of common-envelope evolution, wherein the original orbit is enveloped during the red giant phase and shrinks owing to friction. In this case, however, the long orbital period (compared with other white dwarfs with close brown dwarf or stellar companions) and low mass of the planet candidate make common-envelope evolution less likely. Instead, our findings for the WD 1856+534 system indicate that giant planets can be scattered into tight orbits without being tidally disrupted, motivating the search for smaller transiting planets around white dwarfs.

Pancreatectomy After Neoadjuvant FOLFIRINOX Chemotherapy: Identifying Factors Predicting Long-Term Survival.

INTRODUCTION: We aimed to evaluate the long-term outcomes of the association of neoadjuvant chemotherapy with pancreatectomy with vascular resection in patients with locally advanced pancreatic cancer. METHODS: Clinical data from patients who underwent pancreatic resection after neoadjuvant FOLFIRINOX were retrospectively reviewed. Cox analyses were used to identify factors prognostic of overall survival (OS). RESULTS: FOLFIRINOX protocol was administered pre-operatively with a median number of nine cycles (range 2-18) in 98 patients. Types of resections included pancreaticoduodenectomy (n = 53), total pancreatectomy (n = 17), and distal spleno-pancreatectomy (n = 28). Venous resection and arterial resections were performed in 85 (86.7%) and 64 patients (65.3%), respectively. The overall 90-day mortality and morbidity rates were 6.1% (n = 6) and 47% (n = 47), respectively. The median OS was 31.08 months after surgery. OS rates at one, three, five, and 10 years were 82%, 47%, 28%, and 21%, respectively. According to the type of vascular resection, median OS and 5-year survival rates were exclusive venous resection (31.08 months; 23%) and arterial resections (24.7 months; 27%). Multivariate Cox analysis found lymph node involvement, venous invasion, and total pancreatectomy as independent prognostic factors for OS. According to the presence of 0 or 1-3 risk factors, 5-year survival (85% vs 16%) and median overall survival rates (not reached versus 24.7 months, respectively) were statistically significantly different (p < 0.0001). CONCLUSIONS: A multimodal treatment, including neoadjuvant FOLFIRINOX combined with pancreatectomy with venous and arterial resection, achieves long term survival rates in patients with locally advanced disease. Surgery, in experienced centers, should be integrated into the treatment of patients with locally advanced pancreatic adenocarcinomas.

Basket clinical trial design for targeted therapies for cancer: a French National Authority for Health statement for health technology assessment.

During the past decade, health technology assessment bodies have faced new challenges in establishing the benefits of new drugs for individuals and health-care systems. A topic of increasing importance to the field of oncology is the so-called agnostic regulatory approval of targeted therapies for cancer (independent of tumour location and histology) granted on the basis of basket trials. Basket trials in oncology offer the advantage of simultaneously evaluating treatments for multiple tumours, even rare cancers, in a single clinical trial. To address the novel challenges introduced by these trials, an interdisciplinary panel was convened on behalf of the Transparency Committee of the French National Authority for Health to clarify an approach designed to guarantee a transparent, reproducible, and fair assessment of histology-agnostic treatments for reimbursement by the French National Health Insurance Fund. The requirements of this approach include the need for randomisation, clinically relevant endpoints, appropriate correction for multiple significance testing, characterisation of subgroup heterogeneity, and validation of underlying biomarker assays. A prospectively designated external control is encouraged when the implementation of a direct comparison is deemed infeasible. We also underline the importance of recording outcomes from basket trials in a registry for use as future external controls.

A disintegrating minor planet transiting a white dwarf.

Most stars become white dwarfs after they have exhausted their nuclear fuel (the Sun will be one such). Between one-quarter and one-half of white dwarfs have elements heavier than helium in their atmospheres, even though these elements ought to sink rapidly into the stellar interiors (unless they are occasionally replenished). The abundance ratios of heavy elements in the atmospheres of white dwarfs are similar to the ratios in rocky bodies in the Solar System. This fact, together with the existence of warm, dusty debris disks surrounding about four per cent of white dwarfs, suggests that rocky debris from the planetary systems of white-dwarf progenitors occasionally pollutes the atmospheres of the stars. The total accreted mass of this debris is sometimes comparable to the mass of large asteroids in the Solar System. However, rocky, disintegrating bodies around a white dwarf have not yet been observed. Here we report observations of a white dwarf--WD 1145+017--being transited by at least one, and probably several, disintegrating planetesimals, with periods ranging from 4.5 hours to 4.9 hours. The strongest transit signals occur every 4.5 hours and exhibit varying depths (blocking up to 40 per cent of the star's brightness) and asymmetric profiles, indicative of a small object with a cometary tail of dusty effluent material. The star has a dusty debris disk, and the star's spectrum shows prominent lines from heavy elements such as magnesium, aluminium, silicon, calcium, iron, and nickel. This system provides further evidence that the pollution of white dwarfs by heavy elements might originate from disrupted rocky bodies such as asteroids and minor planets.

Prognostic significance of residual lymphovascular invasion after resection of locally advanced and borderline resectable pancreatic adenocarcinomas treated by neoadjuvant chemotherapy.

BACKGROUND: The current study aimed to identify histological prognostic factors after resection of locally advanced (LA) and borderline (BL) pancreatic adenocarcinomas treated by neoadjuvant chemotherapy (NC). METHODS: A retrospective review was performed of patients with LA and BL adenocarcinomas operated after NC between January 2010 and April 2018. Prognostic factors for survival were assessed by multivariate Cox analysis. RESULTS: Of the 84 patients, 29 had BL and 55 had LA pancreatic adenocarcinomas. Seventy-five patients underwent synchronous venous resection and 57 underwent arterial resection. The median overall survival from surgery was 21.10 months (BL 23-LA 21) (95% CI: 14.8-30.3) with 1-, 3-, and 5-year overall survival rates of 73%, 32%, and 20%, respectively. Multivariate analysis identified lymphovascular invasion (LVI) as an independent prognostic factor for overall survival (HR: 2.32, 95% CI: 1.28-4.22; p = 0.004). Patients without LVI (n = 37) had superior median overall and 5-year survival rates (31.0 months [40 from diagnosis]; 39%) compared to patients with LVI (n = 47; 14.4 months [22 from diagnosis]; 7%). The absence of residual LVI was associated with major pathologic response rates (p < 0.05). CONCLUSION: The persistence of LVI at pathology after resection of LA and BL treated by neoadjuvant chemotherapy predicts poor response and limited long-term survival.

Pancreatectomy With Arterial Resection for Pancreatic Adenocarcinoma: How Can It Be Done Safely and With Which Outcomes?: A Single Institution's Experience With 118 Patients.

OBJECTIVE: This study assesses the safety and outcomes of the largest cohort of pancreatectomy with arterial resection (P-AR). BACKGROUND: A high postoperative mortality rate and uncertain oncologic benefits have limited the use of P-AR for locally advanced pancreatic adenocarcinoma. METHODS: We retrospectively reviewed a prospectively maintained database of patients who underwent P-AR between January 1990 and November 2017. Univariate and multivariate Cox analyses were used to assess prognostic factors for survival. RESULTS: There were 118 consecutive resections (51 pancreaticoduodenectomies, 18 total pancreatectomies, and 49 distal splenopancreatectomies). Resected arterial segments included the coeliac trunk (50), hepatic artery (29), superior mesenteric artery (35), and other segments (4). The overall mortality and morbidity were 5.1% and 41.5%, respectively. There were 84 (75.4%) patients who received neoadjuvant chemotherapy, 105 (89%) simultaneous venous resections, and 101 (85.5%) arterial reconstructions. The rates of R0 resection and pathologic invasion of venous and arterial walls were 52.4%, 74.2%, and 58%, respectively. The overall survival was 59%, 13%, and 11.8% at 1, 3, and 5 years, respectively. The median overall survival after resection was 13.70 months (CI 95%:11-18.5 mo). In multivariate analysis, R0 resection (HR: 0.60; 95% CI: 0.38-0.96; P = 0.01) and venous invasion (HR: 1.67; 95% CI: 1.01-2.63; P = 0.04) were independent prognostic factors. CONCLUSION: In a specialized setting, P-AR for locally advanced pancreatic adenocarcinoma can be performed safely with limited mortality and morbidity. Negative resection margin and the absence of associated venous invasion might predict favorable long-term outcomes.

Resection of Borderline Resectable and Locally Advanced Pancreatic Adenocarcinomas after Neoadjuvant Chemotherapy.

OBJECTIVE: To report the outcomes of surgical resection of borderline resectable (BL) and locally advanced (LA) 'unresectable' pancreatic cancer after neoadjuvant chemotherapy. METHODS: A review of a prospectively maintained database for pancreatic resections was undertaken to identify patients undergoing resection for BL and LA pancreatic cancer after neoadjuvant chemotherapy between January 2007 and December 2012. Clinicopathological, surgical and survival outcomes were analyzed. RESULTS: A total of 45 patients with LA (n = 34) or BL cancer (n = 11) underwent surgery after a mean (± SD) of 7 ± 4 preoperative chemotherapy cycles. Ninety-day mortality was 6.7%, and overall morbidity was 33.3%. An R0 resection was achieved in 34 patients, and 4 patients showed a complete pathological response. Overall median postoperative survival was 17 months (21 after the start of neoadjuvant treatment). Overall and disease-free survival was 74.9 and 43.6% at 1 year and 21.2 and 10.3% at 3 years, respectively. In BL cancer patients, the 3-year survival was significantly higher compared to that of LA cancer patients (p = 0.02). CONCLUSIONS: Curative intent resection in BL and LA cancer patients after neoadjuvant chemotherapy can be achieved with reasonable mortality and morbidity and an encouraging 3-year survival. After neoadjuvant therapy, resection provides a better overall survival for BL compared to LA cancer patients.

Resection of pancreatic adenocarcinomas with synchronous liver metastases: A retrospective study of prognostic factors for survival.

BACKGROUND: This study aimed to evaluate the results of synchronous liver resection for metastatic pancreatic ductal adenocarcinomas and to identify prognostic factors for overall survival. METHODS: We retrospectively reviewed clinical data from patients who underwent the synchronous resection of pancreatic adenocarcinoma with liver metastases. Cox analyses were used to identify factors prognostic of overall survival. RESULTS: Of the 92 patients included in this study, preoperative chemotherapy was administered to 52 patients. The median overall survival was 18.26 months (95% confidence interval: 14.7-22.7) (from diagnosis) and 12.68 months (95% confidence interval: 9.5-15.57) from surgery; overall survival at 1, 3, and 5 years was 70%, 10%, and 0%, respectively. Twenty-eight patients (30.4%) had median overall survival >18 months after surgery. The median overall survival from diagnosis was longer in patients undergoing preoperative treatment (22.7 vs 13.8 months; P = .01) but similar after surgery (12.6 vs 13.8 months; P = .86). Multivariate Cox analysis found CA19-9 levels <500 kU/L (hazard ratio: 0.35; 95% confidence interval: 0.17-0.70; P = .003), R0 resection (hazard ratio: 0.46; 95% confidence interval: 0.24-0.88; P = .020), and adjuvant chemotherapy (hazard ratio: 0.39; 95% confidence interval: 0.17-0.88; P = .024) as independent prognostic factors for overall survival. CONCLUSION: Survival after resection of oligometastatic liver disease remains limited, reflecting the dismal prognosis of metastatic disease even after aggressive treatment. Preresection CA19-9 serum levels represent a useful tool for patient selection, and administration of adjuvant chemotherapy has a major impact on overall survival. Large comparative studies with exclusive chemotherapy are needed to validate this approach and to identify optimal candidates.

Upfront versus resection after neoadjuvant chemotherapy for pancreatic adenocarcinomas with venous contact: comparative analysis of operative and survival outcomes.

BACKGROUND: Neoadjuvant treatment before resection for pancreatic adenocarcinoma having contact with the splenomesentericoportal venous axis could improve the results of extended pancreatectomies. We compared the outcomes of upfront (UR) and resection after neoadjuvant chemotherapy (NAC) for pancreatic adenocarcinoma. METHODS: We retrospectively reviewed clinical data of patients who underwent pancreaticoduodenectomy with venous resection for pancreatic adenocarcinoma between January 1, 2006, and December 31, 2020. Operative, pathologic, and survival outcomes were compared between upfront and resection after neoadjuvant chemotherapy. RESULTS: Of the 169 patients, 55 patients underwent preoperative chemotherapy and 114 underwent upfront. No differences were found in operative time, morbidity, and mortality between the 2 groups. At pathologic examination, patients who underwent resection after neoadjuvant chemotherapy had a significantly smaller tumor size, higher rate of R0 resection, less lymph node involvement, and a lower rate of pathologic venous invasion (P < .05). The median overall survival was 27.96 months, and the overall survival rates at 1, 3, 5, and 10 years were 82%, 39%, 22%, and 11%, respectively. Multivariate Cox analysis found neoadjuvant treatment (hazard ratio: 0.60; 95% confidence interval: 0.38-0.97; P = .03), and intraoperative transfusion (hazard ratio: 2.25; 95% confidence interval: 1.47-3.46; P = .0002) as independent prognostic factors for overall survival. A dose-dependent effect of perioperative transfusion on overall survival was found (no transfusion, = 2 red blood cells, >2 red blood cells; median overall survival 41.1 months vs 27.01 months vs 19.4 months; P = .0003). CONCLUSION: Neoadjuvant chemotherapy improves the pathologic and survival outcomes of pancreaticoduodenectomy with venous resection for pancreatic adenocarcinomas. The dose-dependent effect of perioperative transfusion on overall survival warrants further investigation.

New strategies for medical management of castration-resistant prostate cancer.

Although advanced prostate cancer patients respond very well to front-line androgen deprivation, failure to hormonal therapy most often occurs after a median time of 18-24 months. The care of castration-resistant prostate cancer (CRPC) has significantly evolved over the past decade, with the onset of first-line therapy with docetaxel. Although numerous therapy schedules have been investigated alongside docetaxel, in either first-line or salvage therapy, results were dismal. However, CRPC chemotherapy is currently evolving, with, on the one hand, new agents targeting androgen metabolism and, on the other hand, significant progress in chemotherapy drugs, particularly for second-line therapy. The aim of the present review is to describe the current treatments for CRPC chemotherapy alongside their challengers that might shortly become new standards. In this article, we discuss the most recent data from clinical trials to provide the reader with a comprehensive, state-of-the-art overview of CRPC chemotherapy and hormonal therapy.

Adjuvant gemcitabine versus NEOadjuvant gemcitabine/oxaliplatin plus adjuvant gemcitabine in resectable pancreatic cancer: a randomized multicenter phase III study (NEOPAC study).

BACKGROUND: Despite major improvements in the perioperative outcome of pancreas surgery, the prognosis of pancreatic cancer after curative resection remains poor. Adjuvant chemotherapy increases disease-free and overall survival, but this treatment cannot be offered to a significant proportion of patients due to the surgical morbidity. In contrast, almost all patients can receive (neo)adjuvant chemotherapy before surgery. This treatment is safe and effective, and has resulted in a median survival of 26.5 months in a recent phase II trial. Moreover, neoadjuvant chemotherapy improves the nutritional status of patients with pancreatic cancer. This multicenter phase III trial (NEOPAC) has been designed to explore the efficacy of neoadjuvant chemotherapy. METHODS/DESIGN: This is a prospective randomized phase III trial. Patients with resectable cytologically proven adenocarcinoma of the pancreatic head are eligible for this study. All patients must be at least 18 years old and must provide written informed consent. An infiltration of the superior mesenteric vein > 180° or major visceral arteries are considered exclusion criteria. Eligible patients will be randomized to surgery followed by adjuvant gemcitabine (1000 mg/m(2)) for 6 months or neoadjuvant chemotherapy (gemcitabine 1000 mg/m(2), oxaliplatin 100 mg/m(2)) followed by surgery and the same adjuvant treatment. Neoadjuvant chemotherapy is given four times every two weeks. The staging as well as the restaging protocol after neoadjuvant chemotherapy include computed tomography of chest and abdomen and diagnostic laparoscopy. The primary study endpoint is progression-free survival. According to the sample size calculation, 155 patients need to be randomized to each treatment arm. Disease recurrence will be documented by scheduled computed tomography scans 9, 12, 15, 21 and thereafter every 6 months until disease progression. For quality control, circumferential resection margins are marked intraoperatively, and representative histological sections will be centrally reviewed by a dedicated pathologist. DISCUSSION: The NEOPAC study will determine the efficacy of neoadjuvant chemotherapy in pancreatic cancer for the first time and offers a unique potential for translational research. Furthermore, this trial will provide the unbiased overall survival of all patients undergoing surgery for resectable cancer of the pancreatic head. TRIAL REGISTRATION: clinicalTrials.gov NCT01314027.

Evolving standards of care in advanced gastric cancer.

Despite its decreasing incidence in western countries, the care of gastric cancer remains a concern, as many patients are diagnosed with advanced disease. Whereas localized gastric cancer has benefited from advances in surgical management and perioperative chemotherapy, patients with unresectable or metastatic disease have a poor prognosis. However, advances in chemotherapy have still arisen, with the onset of more convenient and active schedules of treatment, but no significant breakthrough has been achieved in terms of survival. Recent trials in advanced gastric cancer have been focusing on targeted therapies. This article aims to focus on the current state of the art in terms of chemotherapy for advanced gastric cancer, as well as to describe and explain the rationale and hopes for newer therapies that are currently under investigation.

Semi-quantitative evaluation of estrogen receptor expression is a strong predictive factor of pathological complete response after anthracycline-based neo-adjuvant chemotherapy in hormonal-sensitive breast cancer.

Absence of hormonal receptors (HR) expression is a predictive factor of high pathologic complete response (pCR) rate after neo-adjuvant chemotherapy. However, HR-positive tumors are less chemosensitive. In the present study, we evaluated the predictive value of estrogen (ER) and progesterone (PgR) semi-quantitative expression in patients with HR-positive tumors treated uniformly with antracycline-based neoadjuvant chemotherapy without hormonal treatment. Value of HR expression as a predictive factor was then evaluated in a multivariate analysis with tumor grade, Ki67 index and HER2 expression. From January 2000 and December 2006, 177 patients with HR-positive breast ductal invasive carcinoma ≥2 cm in its largest diameter were treated with six cycles of an anthracycline-based neo-adjuvant chemotherapy. Tumor grade, ER, PgR, HER2 status and Ki67 index were determined on microbiopsy performed before chemotherapy. A semi-quantitative evaluation of ER and PgR expression by IHC was performed using the Barnes'score. pCR rate was significantly different (P < 0.001) according to the ER expression score. pCR rate was 28% for low score, 9% for medium score and 3% for high score. On the contrary, pCR rate was not significantly different (P = 0.49) according to the PgR expression score. In the multivariate analysis, ER expression score (P = 0.0002) and Ki67 index (P = 0.02) were the only predictive factors of response for HR-positive tumors. pCR after anthracycline-based chemotherapy is significantly correlated with the ER expression score.

The left splenorenal venous shunt decreases clinical signs of sinistral portal hypertension associated with splenic vein ligation during pancreaticoduodenectomy with venous resection.

BACKGROUND: The ligation of the splenic vein during pancreaticoduodenectomy with synchronous resection of the spleno-mesenteric-portal venous confluence has been associated with the development of left portal hypertension despite preservation of the natural confluence with the inferior mesenteric vein. This study aimed to assess whether a left splenorenal venous shunt might mitigate clinical signs of left portal hypertension associated with splenic vein ligation. METHODS: We retrospectively evaluated the presence of left portal hypertension based on biologic and radiologic parameters in patients undergoing pancreaticoduodenectomy with synchronous resection of the spleno-mesentericoportal confluence between January 1, 2012, and December 31, 2018. We compared several parameters between patients undergoing splenic vein ligation with preservation of the inferior mesenteric vein confluence and a splenorenal venous shunt: the early and late spleen volumes and spleen volume ratios, an early and late platelet count, the presence of thrombocytopenia, the presence of varices, and digestive bleeding in the long-term. RESULTS: There were 114 consecutive patients: 36 with splenic vein ligation and 78 with splenorenal venous shunt. All had a pancreaticogastrostomy. Patients with splenic vein ligation had a comparable baseline and early and late platelet counts. Although baseline splenic volumes were comparable between the 2 groups (242 ± 115 mL vs 261 ± 138 mL; P = .51), patients with splenic vein ligation showed a statistically significant greater splenic volume beyond the 6th postoperative months (334 ± 160 mL vs 241 ± 111 mL; P = .004), higher early and late spleen volume ratios (1.42 ± 0.67 vs 1.10 ± 0.3; P = .001 and 1.38 ± 0.38 vs 0.97 ± 0.4; P = .0001) than patients with splenorenal venous shunt. Splenic vein ligation was also associated with a higher rate of varices (81% vs 50%; P = .002) and more frequent varices with a caliber greater than 1 cm (57% vs 36%; P = .05) and more colonic varices (33% vs 12%; P = .01). Only 1 patient had long-term digestive bleeding (splenic vein ligation). CONCLUSION: The left splenorenal shunt decreases clinical signs of left portal hypertension associated with splenic vein ligation and inferior mesenteric vein confluence preservation.

Geriatric oncology: how far have we gone and what are the next steps?

Geriatric oncology is increasingly developing in Western countries as it is established that cancer peaks after 60 years of age, and the populations are inexorably aging. Aging is associated with a decrease in the use of chemotherapy, and some patients are therefore exposed to undertreatment. Comprehensive geriatric assessment is a composite of several scores that target the multidimensional aspects of the old person. With the use of comprehensive geriatric assessment, geriatricians and oncologists can tailor treatment to their patients. In this review, we briefly describe the characteristics of elderly cancer patients, and identify the pitfalls of anticancer treatment in elderly patients. In light of our expertise, we describe the benefits that can be awaited from joint efforts from geriatricians and oncologists and suggest future directions to answer unmet needs.

High-LET radiation combined with oxaliplatin induce autophagy in U-87 glioblastoma cells.

Modern protocols of concomitant chemo/radiotherapy provide a very effective strategy to treat certain types of tumors. High-linear energy transfer (LET) radiations, on the other hand, have an increased efficacy against cancer with low radiosensibility and critical localization. We previously reported that oxaliplatin, a third generation platinum drug, was able to reinforce the cytotoxicity of an irradiation by fast neutrons towards human glioblastoma U-87 cells in culture. We show here that such a combination has the capacity to enhance the number of double strand breaks in DNA and to induce autophagy in these cells. Xenografts experiments were further performed in nude mice subcutaneously transplanted with U-87 cells. When injected shortly before a single irradiation by fast neutrons, oxaliplatin causes a marked reduction of tumor growth compared with the irradiation alone. Overall, our data indicate the unique cytotoxic mechanism of a combined high-LET irradiation and oxaliplatin treatment modality and suggest its potential application in anticancer therapy.

The cytotoxicity of high-linear energy transfer radiation is reinforced by oxaliplatin in human glioblastoma cells.

The combination of high-linear energy transfer (LET) radiation with chemotherapeutic agents may offer new perspectives in cancer treatment. We therefore assessed the consequences of a treatment in which U-87 human glioblastoma cells were irradiated with p(65)+Be neutrons in the presence of oxaliplatin, a third generation platinum anticancer drug having higher apoptosis-inducing activity than cisplatin. Cell survival, apoptosis, cell cycle progression as well as p21 and p53 protein expressions were analyzed. Results show that an enhanced cytotoxic effect was obtained when the two treatments were combined and that, unlike what we previously observed with cisplatin, this was not due to a reinforcement of apoptosis. Altogether, our results also indicate the potential of oxaliplatin for use in association with high-LET radiation against tumors refractory to conventional photon radiotherapy.

Cell death induced in a human glioblastoma cell line by p(65)+Be neutrons combined with cisplatin.

High linear energy transfer (LET) radiation have the ability to kill cancer cells resistant to conventional radiotherapy. On the other hand, protocols combining radiotherapy and chemotherapy are effective in eradicating certain inoperable cancers. In this study, we investigated the cytotoxicity of a co-treatment with fast neutrons and cisplatin in a human glioblastoma cell line, U-87. Cells cultured in vitro were irradiated with p(65)+Be neutrons in the presence of cisplatin. Cell survival and the induction of apoptosis and premature senescence were assessed at different time intervals thereafter, using a variety of methods. A marked reinforcement of the cytotoxicity was obtained when irradiation and cisplatin were associated. This reflected both an amplification of the apoptotic process and the induction of premature cell senescence. The efficiency of a combination between fast neutrons and cisplatin in inducing cell death in U-87 is more than additive. The present data concur with those we previously reported in a mouse lymphoma and suggest the potential utility of platinum compounds as adjuncts to future cancer therapy protocols using high-LET radiation.

Aspergillus galactomannan detection in the diagnosis of invasive aspergillosis in cancer patients.

PURPOSE: To assess the Aspergillus galactomannan enzyme-linked immunosorbent assay (ELISA) in the diagnosis of invasive aspergillosis (IA) in adult and pediatric oncohematologic patients. PATIENTS AND METHODS: The study was conducted in four patient groups: those with fever of unknown origin (FUO) during neutropenia, suspected pulmonary infection (PI), or nonpulmonary aspergillosis (NPA) and those undergoing surveillance (S) after hematopoietic stem-cell transplantation (HSCT). IA was classified as definite, probable, or possible, according to European Organization for Research and Treatment of Cancer/Mycosis Study Group definitions. RESULTS: A total of 3,294 serum samples were collected during 797 episodes (FUO, 261; PI, 297; NPA, 28; and surveillance, 211), and 153 episodes of IA were diagnosed (31 definite, 67 probable, and 55 possible). Three episodes were first suspected from galactomannan ELISA; the remaining 150 cases were diagnosed from clinical or radiologic evidence. Sensitivity of the ELISA was 64.5%, 16.4%, and 25.5% in definite, probable, and possible episodes of IA, respectively, and was lower in patients positive for anti-Aspergillus antibodies than in antibody-negative patients. Most false-positive results occurred in children and in allogeneic HSCT (allo-HSCT) patients. Overall specificity of the ELISA was 94.8%. It was lower in children compared with adults (P <.0001) and in allo-HSCT patients compared with non-allo-HSCT adults (P =.0002). Lowering the ELISA cutoff value from 1.500 to 0.700 seemed more relevant for non-allo-HSCT adults (sensitivity, 73.1%, 44.3%, and 44.7% in definite, probable, and possible IA, respectively; specificity, 94%). CONCLUSION: Galactomannan ELISA seems less sensitive than previously described, and sensitivity can be further reduced by the presence of anti-Aspergillus antibodies. A new cutoff value for the ELISA of 0.700 is proposed for non-allo-HSCT adults.