Immune checkpoint inhibitor treatment of a first cancer is associated with a decreased incidence of second primary cancer.

BACKGROUND: Second primary cancers (SPCs) are diagnosed in over 5% of patients after a first primary cancer (FPC). We explore here the impact of immune checkpoint inhibitors (ICIs) given for an FPC on the risk of SPC in different age groups, cancer types and treatments. PATIENTS AND METHODS: The files of the 46 829 patients diagnosed with an FPC in the Centre Léon Bérard from 2013 to 2018 were analyzed. Structured data were extracted and electronic patient records were screened using a natural language processing tool, with validation using manual screening of 2818 files of patients. Univariate and multivariate analyses of the incidence of SPC according to patient characteristics and treatment were conducted. RESULTS: Among the 46 829 patients, 1830 (3.9%) had a diagnosis of SPC with a median interval of 11.1 months (range 0-78 months); 18 128 (38.7%) received cytotoxic chemotherapy (CC) and 1163 (2.5%) received ICIs for the treatment of the FPC in this period. SPCs were observed in 7/1163 (0.6%) patients who had received ICIs for their FPC versus 437/16 997 (2.6%) patients receiving CC and no ICIs for the FPC versus 1386/28 669 (4.8%) for patients receiving neither CC nor ICIs for the FPC. This reduction was observed at all ages and for all histotypes analyzed. Treatment with ICIs and/or CC for the FPC are associated with a reduced risk of SPC in multivariate analysis. CONCLUSION: Immunotherapy with ICIs alone and in combination with CC was found to be associated with a reduced incidence of SPC for all ages and cancer types.

Updated recommendations of the International Society of Geriatric Oncology on prostate cancer management in older patients.

BACKGROUND: The median age of prostate cancer diagnosis is 66 years, and the median age of men who die of the disease is eighty years. The public health impact of prostate cancer is already substantial and, given the rapidly ageing world population, can only increase. In this context, the International Society of Geriatric Oncology (SIOG) Task Forces have, since 2010, been developing guidelines for the management of senior adults with prostate cancer. MATERIAL AND METHODS: Since prostate cancer and geriatric oncology are both rapidly evolving fields, a new multidisciplinary Task Force was formed in 2018 to update SIOG recommendations, principally on health status screening tools and treatment. The task force reviewed pertinent articles published between June 2016 and June 2018 and abstracts from European Association of Urology (EAU), European Society for Medical Oncology (ESMO), American Society of Clinical Oncology (ASCO) and American Society of Clinical Oncology Genito-urinary (ASCO GU) meetings over the same period, using search terms relevant to prostate cancer, the elderly, geriatric evaluation, local treatments and advanced disease. Each member of the group proposed modifications to the previous guidelines. These were collated and circulated. The final manuscript reflects the expert consensus. RESULTS: The 2019 consensus is that men aged 75 years and older with prostate cancer should be managed according to their individual health status, and not according to age. Based on available rapid health screening tools, geriatric evaluation and geriatric interventions, the Task Force recommends that patients are classified according to health status into three groups: (1) 'healthy' or 'fit' patients should have the same treatment options as younger patients; (2) 'vulnerable' patients are candidates for geriatric interventions which-if successful-may make it appropriate for them to receive standard treatment and (3) 'frail' patients with major impairments who should receive adapted or palliative treatment. The 2019 SIOG Task Force recommendations also discuss prospects and unmet needs for health status evaluation in everyday practice in older patients with prostate cancer.

[Does consumption of tobacco, alcohol, and cannabis in adolescents and young adults with cancer affect the use of analgesics during hospitalizations?]. / La consommation de tabac, alcool et cannabis chez les adolescents et jeunes adultes atteints de cancer a-t-elle un impact sur l'utilisation hospitalière des traitements antalgiques pendant la période de traitement ?

INTRODUCTION: The specificities of adolescents and young adults (AYAs) aged 15-25 years with cancer are now well recognized. Dedicated care was initiated in 2012 in France under the leadership of the INCa (National Cancer Institute). Research on supportive care and particularly pain management are still rare. This study aimed to evaluate the consumption of toxic substances (tobacco, cannabis, alcohol) in AYAs with cancer as well as its progression during the month following the diagnosis and to analyze its influence on opioid analgesic prescriptions during treatment. METHODS: This is a prospective study including all new patients aged 15-25 years in two centers between January and June 2013. Data on consumption of psychoactive substances were obtained during an individual interview with a questionnaire. National surveys were used to compare this cohort with the general population. Data on opioid treatments were collected from the computerized prescription software and computerized patient record. RESULTS: Thirty-seven AYAs were eligible and 30 were included; 67% of them were male and the median age was 18.7 years. The questionnaire on tobacco, alcohol, and cannabis consumption at diagnosis was well accepted. Consumption profiles were comparable to the general population. Changes in behavior were observed during the 1st month after diagnosis, with a decrease or cessation of consumption, particularly among young people. This study showed differences in the use and requirements for opioid analgesics during hospitalization according to these consumption data. CONCLUSION: Prevention and support for AYAs who are regular consumers of toxic substances must be organized during initial care in oncology.

Management of brain metastases from germ cell tumors: a single center experience.

BACKGROUND: Brain metastases from germ cell tumors (GCT) are rare and treatment has not yet been standardized. METHODS: The clinical data of men with brain metastases from GCT treated in a single cancer hospital from January 1993 to September 2007 were reviewed. Patients with primary central nervous system GCT were excluded. RESULTS: Thirteen patients had brain metastases at initial diagnosis. All patients received cisplatin-based chemotherapy. Three also received radiotherapy and 1 underwent surgery. Eight of the patients died. Median survival was 19 months (95% CI 0.84-not reached). Twenty-two patients developed brain metastases at recurrence. Median time from initial diagnosis to brain metastases was 8.25 months (3-17.5 months). Five patients received radiotherapy alone, 3 received chemotherapy alone and 3 received supportive care only. Nine patients were operated on: 6 received postoperative chemotherapy and 1 received postoperative radiotherapy. Only 1 patient is still alive. Median survival was 5.1 months (95% CI: 2.2-10.5 months). CONCLUSIONS: Patients with GCT who present with brain metastases at diagnosis tend to do better than patients who develop them at relapse. Chemotherapy can be adequate treatment for initial brain metastases. Treatment for patients with brain metastases at relapse is still not optimal.

Addition of bevacizumab to temsirolimus in kidney cancer patients.

Treatment of metastatic kidney cancer has changed dramatically in the past years with the use of VEGF-targeted therapies and mTOR inhibitors. However, resistance occurs. We report here two cases of patients who benefited, both on disease control and side effects, from the addition of bevacizumab to temsirolimus, after progression on the mTOR inhibitor alone.

Treatment of uncommon malignant tumours of the bladder.

PURPOSE OF REVIEW: Urothelial carcinoma is the most common histological type of bladder tumours. Nevertheless, its variants and less common types represent 20% of all bladder cancers. The objective was to update the recent publications on these rare diseases and to draw conclusions for clinical management. RECENT FINDINGS: Recent retrospective studies have been published. They refine the description of histological patterns and of immunochemistry diagnosis. Taking into account the heterogeneity of these pathologies, several groups have benefited of increased knowledge such as sarcomas and lymphomas. The need of international collaboration to study prospectively some subgroups of tumours is crucial. SUMMARY: Rare bladder cancers have generally poor outcome and in a majority of the cases surgery, namely cystectomy remains the most important curative treatment. Specific subgroups, as lymphoma, sarcoma and dedifferentiated epithelial tumours may benefit of molecular characterization and trials with targeted drugs.

[Uncommon bladder tumours]. / Tumeurs rares de la vessie.

Bladder tumours are frequent with around 10,000 new cases each year in France. Less than 500 of these cases are not transitional cell carcinoma, the most frequent pathological aspect. The identification of these pathological patterns requires an initial biopsy through transurethral resection. Sarcomatoid, squamous and some adenocarcinomatous types are often pathological variants of the transitional pattern. These tumours are possibly secondary to alkylating drug metabolites or pelvic radiotherapy and they have often a poor prognostic outcome. This is also the case of spindle cell carcinoma, an endocrine variant of rare bladder cancers. The treatment is generally based on an aggressive approach combining chemotherapy and a radical cystectomy. Other tumours have a more locally invasive pattern, as have urachal adenocarcinomas, sarcomas. The treatment is based on aggressive surgical exeresis of the tumour and surrounding structures. The outcome may be more favourable. Primary non Hodgkin lymphomas are rare, secondary involvement more frequent. All histological subtypes could be encountered. The treatment is the same as this of lymphomas of other location and of the same histology. Attention must be drawn on a precise evaluation of the pathological pattern and of the disease extension.

[Management of side effects associated with antiangiogenic treatment in renal cell carcinoma]. / Gestion des toxicités des antiangiogéniques dans le traitement des cancers du rein.

The recent development of antiangiogenic agents has revolutionized the management of renal cell carcinoma. In less than two-years, the French health authorities have approved the use of four drugs (sorafenib, sunitinib bevacizumab, temsirolimus) for the treatment of locally advanced or metastatic renal cell carcinoma. A fifth drug (everolimus) should be on the market some time. Clinicians have changed their practice and are faced with a number of new adverse events. The management of toxic effects is essential to ensure treatment compliance and patient quality of life. The present report describes in detail the adverse events associated with each therapeutic class and the management of side effects.

Why do residents choose the medical oncology specialty? Implications for future recruitment--results of the 2007 French Association of Residents in Oncology (AERIO) Survey.

BACKGROUND: The aim of this study was to analyze demography, motivation behind the choice of the medical oncology specialty, career plans, and the quality of training in medical oncology and to provide guidance to candidates for boosting the number of oncologists. METHODS: In 2007, the French Association of Residents in Oncology conducted a nationwide study of all medical oncology residents in France. RESULTS: The strongest factors that had influenced their decision to become a medical oncology specialist were an interest in medical oncology (98%), exposure to this branch of medicine during graduate training as a medical student (83%), interest in research (81%), and the diversity of the activity (75%). The mean score for the quality of training was 6 (0-10). More time for reading during working hours as well as for attending staff meetings and greater availability of teaching oncologists would improve the quality of training. The most popular career choice was working in a public hospital but most residents stated that they had not received adequate information about the different career plans. CONCLUSIONS: No data are available regarding how training in medical oncology is perceived. This study provides useful data for future policies to boost the number of oncologists.

Platelet-activating factor does not mediate circulatory failure induced by 35-GHz microwave heating.

Sustained whole-body exposure of anesthetized rats to 35-GHz radiofrequency radiation produces localized hyperthermia and hypotension, leading to circulatory failure and death. The physiological mechanism underlying the induction of circulatory failure by 35-GHz microwave (MW) heating is currently unknown. The purpose of this study was to determine whether platelet-activating factor (PAF) contributes to the hypotensive state induced by MW heating. Ketamine-anesthetized rats were instrumented for the measurement of arterial blood pressure, ECG and temperature at five sites. Administration of the PAF-receptor antagonist WEB 2086 (0.5 or 5 mg/kg) following the induction of circulatory failure (defined as a decrease in mean arterial blood pressure to 75 mmHg) failed to reverse the hypotension induced by MW heating and consequently did not alter the subsequent survival time. Furthermore, pretreatment with WEB 2086 at either dose did not alter subsequent mean arterial blood pressure, temperature responses to MW heating or survival time. Finally, MW heating did not alter either blood PAF levels or serum or lung PAF acetylhydrolase levels. Taken together, these results demonstrate that PAF does not mediate the hypotension induced by 35-GHz MW heating.

Human placental GnRH-like factors: parallel displacement in GnRH immuno- and receptor-binding assays can be caused by degradation of radiolabelled GnRH tracers.

Human term placental cytosol fractions decreased the specific binding of gonadotrophin-releasing hormone (GnRH) isoform tracers to placental membranes (and to rat pituitary GnRH receptors and anti-GnRH antibodies) in a dose-dependent manner, and in parallel to GnRH standard curves. However, cytosol fractions had little or no effect on the binding of two GnRH superagonist tracers. The specificity of placental binding sites for a range of GnRH-like and unrelated peptides was shown to be similar with GnRH isoforms or GnRH agonists as binding ligands, suggesting that isoforms and agonists did not bind to different forms of the GnRH-receptor. Inclusion of a cocktail of protease inhibitors during the preparation of placental cytosol significantly reduced immuno- and receptor-binding activity. Moreover, incubation of radiolabelled chicken GnRH II with placental cytosol led to marked inactivation of tracer, as assessed by radioreceptor and radioimmunoassays for GnRH, high resolution liquid chromatography, thin layer chromatography and adsorption to dextran-coated charcoal and other matrices. There was a good negative correlation between tracer degradation and apparent GnRH immuno- and receptor-binding activities. These results emphasize the important effects which proteases in un-denatured tissue extracts can have on radioreceptor and radioimmunoassays due to inactivation of peptide tracers, and suggest that previous measurements of receptor- and immuno-active GnRH-like factors may have been over-estimated due to peptidase action during the GnRH assay.

Characterization and identification of black alder ectomycorrhizas by PCR/RFLP analyses of the rDNA internal transcribed spacer (ITS).

The identity of black alder (Alnus glutinosa (L.) Gaertn.) ectomycorrhizas was investigated using PCR/RFLP analysis of the ITS region from 16 morphotypes sampled at a 60-yr-old black alder stand. A comparison was made with restriction patterns from sporocarps of 28 mycobionts, of which 16 originated from the same stand, the remaining 12 came from two geographically distant alder stands. Eight of the mycorrhizal types could thus be identified, whereas eight mycorrhizal types remained unidentified. The identified mycorrhizas belonged to the genera Russula, Lactarius, Naucoria and Cortinarius. Four of the identified ectomycorrhizal types had identical PCR/RFLP profiles to corresponding fruit bodies from all investigated stands with no detectable intraspecific variation, despite the geographical distance of c.300 km between the sampling locations. By contrast, intraspecific variation between sporocarps from the different locations was detected in Paxillus rubicundulus, mycorrhizas of which were not found. The diversity of fruiting alder mycobionts at the main experimental plot only partly matched the diversity observed from mycorrhizas when comparing their PCR/RFLP profiles. The results are discussed regarding sampling techniques, PCR/RFLP analyses and ecological aspects.

The prevalence of previous sexual assault among routine female attenders at a department of genitourinary medicine.

One hundred and fifty women who attended the routine genitourinary medicine (GUM) clinic at the Leicester Royal Infirmary (LRI) between August 1993 and February 1994 completed a questionnaire enquiring into a past history of sexual assault. Of these, 52 (34.7%) confirmed that they had been assaulted previously, 18 below the age of 16, 22 after this age and 12 in both age groups. Non penetrative abuse was most common in those violated as minors and vaginal penetration in women assaulted over the age of 16. The strongest demographic indicator for sexual abuse among this study group was that of a current divorced/separated marital status. Assailants of minors were most likely to be someone known to the family whereas male intimates accounted for a third of assaults on older women. Sexual dysfunction was acknowledged by approximately half of those previously assaulted as a sequelae of abuse. It is important that GUM physicians remain alert for sequelae of sexual abuse and offer services appropriate to the victim's needs.

Prior sexual assault reported by male attenders at a department of genitourinary medicine.

One-hundred-and-fifty male patients who attended the department of genitourinary medicine (GUM) completed a questionnaire which enquired into a past history of sexual assault and asked certain details about the assault and various sequelae of such an experience. Twenty-one men gave a history of sexual assault, 11 of whom had been abused before the age of 16, 7 afterwards and 3 in both age groups. Victims of such an assault were more likely to be homosexual or bisexual than heterosexual. The substantial majority i.e. 104 (81%) of the 129 patients who had not been assaulted in the past had been brought up by both natural parents. However, of the 21 males who reported a history of previous sexual abuse only 11 (52%) had been raised by both natural parents alone and 9 of the remaining 10 who divulged such information had been brought up in other circumstances. The association between not being raised entirely by both natural parents and a history of previous sexual assault was significant (P < 0.01). Overall, physical contact of a sexual nature was the most commonly reported type of abuse, followed by anal and then by oral penetration. All of the perpetrators of assault were male except in one instance. Only 3 cases of assault were reported to the police or other agencies. Those who had been abused as minors were more likely to acknowledge subsequent psychological difficulties and to have obtained professional counselling. This problem is a significant one which goes largely undetected in GUM departments and elsewhere.(ABSTRACT TRUNCATED AT 250 WORDS)

1H NMR studies of reactions of copper complexes with human blood plasma and urine.

Reactions of the copper complexes Cu(II)Cl2, [Cu(II)(EDTA)]2-, [Cu(II)2(DIPS)4] and [Cu(I)(DMP)2]+ (where DIPS is 3,5-diisopropylsalicylate and DMP is 2,9-dimethylphenanthroline) with human blood plasma and urine have been studied by 500 MHz 1H NMR spectroscopy, and CD spectroscopy has been used to monitor the transfer of Cu(II) onto albumin in plasma. The rate of transfer of Cu(II) from [Cu(II)(EDTA)]2- onto albumin as measured by CD (T1/2 26 min, 0.5 mM Cu, 21 degrees), was similar to the rate of Cu(II) binding to amino acids and citrate, and to the rate of formation of [Ca(II)(EDTA)]2- in plasma. Reactions of Cu(II)Cl2 and [Cu(II)2(DIPS)4] in plasma followed a similar course, but were more rapid. The latter complex also appeared to give rise to the displacement of lactate from protein binding. Reactions of copper complexes in plasma therefore involve a range of low Mr ligands as well as albumin, and the ligands play a major role in determining the kinetics of the reactions. These factors, as well as the partitioning of both complexes and displaced ligands into lipoproteins, are likely to play important roles in the molecular pharmacology of copper-containing drugs. In urine, His and formate were involved in EDTA and DIPS displacement from their respective copper complexes, and peaks for free DIPS and [Ca(II)(EDTA)]2- were observed. The complex (Cu(I)(DMP)2]+ appeared to be relatively stable in both plasma and urine.

An NMR analysis of the binding of inhibitors to yeast phosphoglycerate kinase.

The binding of a series of inhibitors to the enzyme phosphoglycerate kinase has been studied using NMR to uncover the binding sites and the effects of binding on the protein conformation. The very effective inhibitor, Suramin, causes the most pronounced changes. The design of inhibitors for mobile proteins is discussed.

A comparison of dosages of norethisterone for synchronization of cycles in a fixed regimen of follicular augmentation and in vitro fertilization.

Twenty-four patients undergoing elective laparoscopic sterilization were randomized in a fixed schedule of follicular augmentation, oocyte recovery, and in vitro fertilization (IVF) using either 2.5 or 10 mg of norethisterone (NE) in the luteal phase of the previous cycle. The objectives of the study were to determine the effect of a synthetic progestin, given for 5 to 14 days beginning on day 21 of the cycle before the IVF cycle, on folliculogenesis, estrogen secretion, the luteinizing hormone (LH) surge, luteal function, and IVF success. It was found that this treatment was easy to administer and well tolerated by patients. At the 10-mg dose, patients uniformly had vaginal bleeding 2 to 4 days after NE, whereas 40% of patients using the 2.5-mg dose bled before NE was discontinued. Significantly lower estrone glucuronide excretion in the early follicular phase and lower luteal phase pregnanediol excretion in patients receiving 10 mg NE suggested a delay or reduction of developing follicles after luteal phase suppression. No spontaneous LH surges were found in the 10-mg group, compared with surges in 5 of the 13 cycles of the 2.5-mg group. There were no differences between regimens in cycle or luteal phase length. It is postulated that NE, by suppressing folliculogenesis in the luteal phase, may provide for a smaller, but more homogenous cohort of follicles available for exogenous stimulation and recovery.

The use of an LHRH agonist, buserelin, in the long-term management of premenstrual syndromes.

Buserelin, an LHRH agonist, was given by nasal spray to 20 women with premenstrual syndrome. In 10 women benefits were such that they continued treatment for periods varying from 5 to 15 months. There were significant improvements in mood and physical symptoms, and side-effects such as hot flushes were mild. The remaining 10 women were all made worse by the spray and stopped it within 2 months. Ovulation was blocked in all women though six showed evidence of ovulation during the first treatment month, and two women later in treatment. Of the long-term group, six eventually became amenorrhoeic, and four continued to menstruate. There was a significant improvement in symptoms during treatment in the long-term group. Physical symptoms continued to be worse before any menstrual bleeding. Mood change lost its relationship to menstruation. The adverse effects in the short-term group were sometimes severe and it is necessary to identify the characteristics of the woman who are likely to show such reactions before recommending this treatment for more general use.