Management Approaches in WHO Grade III Meningioma: A National Oncology Trainees' Collaborative for Healthcare Research (NOTCH) UK Multi-Centre Retrospective Study.

AIMS: WHO Grade 3 (G3) meningiomas are rare tumours with limited data to guide management. This retrospective study documents UK management approaches across 14 centres over 11 years. MATERIALS AND METHODS: Patients with WHO G3 meningioma between 01/01/2008 and 31/12/2018 were identified. Data were collected on demographics, management strategy, adjuvant radiotherapy, approach in recurrence setting and survival. RESULTS: 84 patients were identified. 21.4% transformed from lower-grade disease. 96.4% underwent primary surgical resection, with 20.8% having evidence of residual disease on their post-op MRI. 59.3% of patients underwent adjuvant radiotherapy (RT) following surgical resection. Overall median PFS and OS were 12.6 months and 28.2 months, respectively. Median OS in the group who underwent complete surgical resection was 34.9 months, compared to 27.5 months for those who had incomplete resection (HR 0.58, 95% CI 0.27-1.23, p = 0.15). Median OS was 33.1 months for those who underwent adjuvant RT and 14.0 months for those who did not (HR 0.48, 95% CI 0.27-0.84, p = 0.004). Median adjuvant RT dose delivered was 60Gy (range 12Gy-60Gy), 45.8% of adjuvant RT was delivered using IMRT. At disease relapse, 31% underwent salvage surgery and 29.3% underwent salvage RT. Of those treated with salvage RT, 64.7% were re-treats and all were treated with hypofractionated RT. CONCLUSION: Surgery continues to be the preferred primary management strategy. Post-operative MRI within 48 hours is indicated to assess presence of residual disease and guide further surgical options. Adjuvant radiotherapy plays an important part of the management paradigm in these patients with the data supporting an attached survival advantage. Further surgery and re-irradiation is an option in the disease recurrence setting with radiosurgery frequently utilised in this context.

Problemas con la rotación de opiáceos: sustitución dela metadona por otro opiáceo en pacientes con dolorrelacionado con cáncer / Pitfalls of opioid rotation: substituting another opioid for methadone in patients with cancer pain

La eficacia de la metadona en el dolor relacionado con cáncer ha sido demostrada por numerosos informes de casos y estudios clínicos. La metadona suele utilizarse como medicación opiácea de segunda o tercera fila. Con el creciente uso de la metadona, nos enfrentamos al reto de sustituirla por otros opiáceos como parte de los tratamientos secuenciales con opiáceos. En este artículo presentamos los datos prospectivos de 13 rotaciones consecutivas de metadona a otro opiáceo. La rotación de opiáceos fue seguida por un aumento del dolor y/o disforia severa, sin que pudieran controlarse con un rápido aumento de la dosis del segundo opiáceo, en 12 de los 13 pacientes. Sólo un paciente se mantuvo bien con el segundo opiáceo después de suspender la metadona, mientras que 12 pacientes tuvieron que volver a recibir metadona. Concluimos que la rotación de la metadona a otro opiáceo suele complicarse por un agravamiento del dolor y la presencia de disforia. Estos síntomas no siempre mejoran a pesar de aumentar la dosis del segundo opiáceo. Actualmente no existe un índice de conversión unánimamente aceptado para sustituir la metadona por otro opiáceo. Se necesitan más datos sobre la rotación de metadona a otros opiáceos (AU)

Timing and the control of variation.

Two rat experiments shed light on how variation in behavior is regulated. Experiment 1 used the peak procedure. On most trials, the 1st bar press more than 40 s after signal onset ended the signal and produced food. Other trials lasted much longer and ended without food. On those trials, the variability of bar-press duration increased greatly after the 1st response more than 40 s after signal onset. In Experiment 2, which asked whether the increase was due to the omission of expected reward or the decrease in reward expectation, reward expectation had a strong effect on response duration, whereas omission of expected reward had little effect. In both experiments, response rate and response duration changed independently, suggesting that they reflect different parts of the underlying mechanism. In Experiment 1, response durations implied that timing of the signal was more accurate than the rate-vs.-time function might suggest. Experiment 2 suggested that lowering reward expectation increases variation in response form.

Implementing national standards for cancer pain management: program model and evaluation.

The purpose of this quasi-experimental (pre and posttest) study was to test a model pain management program (PMP) to implement the American Pain Society (APS) quality assurance standards for the management of acute and chronic cancer pain using a continuous quality improvement (CQI) approach to improve professionals' knowledge and skills, patient satisfaction, and to identify areas needing improvement. The sample consisted of 1210 nurse responses and 698 interviews of patients with pain during hospitalization at a major urban cancer center. The PMP provided a structure (standards), educational opportunities, and training in CQI methods. Outcome measures included a patient evaluation questionnaire and concerns checklist; nurse knowledge, attitude and barriers questionnaire; and focus groups to identify areas needing improvement. Significant improvements were found in patients' satisfaction, nurses' knowledge and attitude scores, and reductions in nurses' perceptions of barriers. Focus groups revealed the need for improved communication among disciplines about pain and better assessment of patients unable to self-report. The program met its goal of implementing the APS standards, educating nurses, and identifying "system" problems, and improving overall patient satisfaction.

Ageism in cancer care of the elderly.

This paper explores the existence and effects of ageism on cancer care of the elderly. Cancer-related care for the elderly patient has not been given appropriate attention. Many of our present attitudes are based on how history has treated the elderly. Screening programs often neglect individuals over 65 despite the increased prevalence of cancers in this age group. Little research evaluating age-related toxicities has been conducted, and no age-related guidelines for chemotherapy administration are available. Of the three modalities (chemotherapy, radiation therapy, and surgery), surgery has made the greatest change in practice based on an understanding of the aging process. Increasing prevalence of cancer in patients over 65, coupled with a projected increase in the numbers of uninsured, will change the demographics and the economics of cancer care dramatically. Early detection and prevention programs targeted toward tomorrow's elderly, who are today in their middle years, have the potential to significantly decrease both morbidity and mortality.

Interferon alpha-2a and 5-fluorouracil for advanced colorectal carcinoma. Assessment of activity and toxicity.

Preclinical data showed that the cytotoxic effects of 5-fluorouracil (5-FU) are augmented by interferon (IFN). In a small study, 13 of 17 patients with advanced colorectal cancer responded to a regimen of 5-FU with IFN. Using the same dose and schedule as in this pilot study, 38 previously untreated patients with metastatic colorectal carcinoma were treated with continuous intravenous (IV) infusion of 5-FU 750 mg/m2 daily for 5 days, followed by weekly bolus 5-FU at 750 mg/m2 and subcutaneous IFN at 9 million units three times per week. Of 35 evaluable patients, nine (26%) had a partial response (95% confidence limit, 11% to 41%), with a median response duration of 7.5 months (range, 4.4 to greater than 11.7 months). Seven patients (20%) had a minor response, and ten (28%) had stable disease. The most common toxicities observed were stomatitis (52%) and diarrhea (43%). Neurotoxicity was seen in 34% of patients and consisted of gait disturbance, dizziness, confusion, memory loss, and dementia. Because of toxicity, 84% of patients required a reduction of the IFN dose by at least 50%, and 63% required reduction of the 5-FU dose by at least 25%. Although the combination of 5-FU and IFN in patients with advanced colorectal carcinoma has some activity, the regimen was toxic, and the observed response rate (26%) was not substantially superior to alternative 5-FU programs.

Phase I trial of N-(phosphonacetyl)-L-aspartate, methotrexate, and 5-fluorouracil with leucovorin rescue in patients with advanced cancer.

Based on an animal model to improve the antitumor activity of 5-fluorouracil (FUra), a Phase I study of N-(phosphonacetyl)-L-aspartate, methotrexate, FUra, and leucovorin was conducted on 44 patients. Methotrexate was given in an intermediate dose (250 mg/m2) to overcome potential drug resistance, and N-(phosphonacetyl)-L-aspartate was given at a low dose (250 mg/m2) in order to allow escalation of FUra to toxicity. These two drugs were given 24 h before FUra to enhance maximal incorporation of FUra into RNA. Two schedules of administration were used; one every other week and one weekly for 2 weeks. The every other week schedule was well tolerated, with minimal gastrointestinal and hematological toxicity. However, the weekly for 2 weeks schedule was more toxic with increased mucositis, diarrhea requiring therapy, and decreased performance status of 20% in 4 of 6 patients. There were no responders in the every other week schedule. There was one partial response and three patients with stable disease in four evaluable patients on the weekly for 2 weeks schedule. At 24 h post-N-(phosphonacetyl)-L-aspartate-methotrexate treatment, PRPP levels were doubled in bone marrow biopsies, and increased 2.5- to 25-fold in tumor biopsies. We have currently added uridine rescue to this combination with the hope of further escalating the dose of FUra.

Primary production: Depression of oxygen evolution in algal cultures by organophosphorus insecticides.

Photosynthesis of four estuarine phytoplankters was inhibited by Baytex and Abate (organophosphates), Baygon (carbamate) and DDT (chlorinated hydrocarbon). Responses varied with the algal species and with the insecticide. The order from most to least toxic insecticide was Baytex, Baygon, DDT, Abate and the order from least to most sensitive alga wasC. nana,P. cornutum=S. costatum,D. euchlora.