Patients' needs in proton therapy: A survey among ten European facilities.

Aims: The number of Proton Therapy (PT) facilities is still limited worldwide, and the access to treatment could be characterized by patients' logistic and economic challenges. Aim of the present survey is to assess the support provided to patients undergoing PT across Europe. Methods: Through a personnel contact, an online questionnaire (62 multiple-choice and open-ended questions) via Microsoft Forms was administered to 10 European PT centers. The questionnaire consisted of 62 questions divided into 6 sections: i) personal data; ii) general information on clinical activity; iii) fractionation, concurrent systemic treatments and technical aspects of PT facility; iv) indication to PT and reimbursement policies; v) economic and/ or logistic support to patients vi) participants agreement on statements related to the possible limitation of access to PT. A qualitative analysis was performed and reported. Results: From March to May 2022 all ten involved centers filled the survey. Nine centers treat from 100 to 500 patients per year. Paediatric patients accounted for 10-30%, 30-50% and 50-70% of the entire cohort for 7, 2 and 1 center, respectively. The most frequent tumours treated in adult population were brain tumours, sarcomas and head and neck carcinomas; in all centers, the mean duration of PT is longer than 3 weeks. In 80% of cases, the treatment reimbursement for PT is supplied by the respective country's Health National System (HNS). HNS also provides economic support to patients in 70% of centers, while logistic and meal support is provided in 20% and 40% of centers, respectively. PT facilities offer economic and/or logistic support in 90% of the cases. Logistic support for parents of pediatric patients is provided by HNS only in one-third of centers. Overall, 70% of respondents agree that geographic challenges could limit a patient's access to proton facilities and 60% believe that additional support should be given to patients referred for PT care. Conclusions: Relevant differences exist among European countries in supporting patients referred to PT in their logistic and economic challenges. Further efforts should be made by HNSs and PT facilities to reduce the risk of inequities in access to cancer care with protons.

[Translated article] Role of radiotherapy in the management of spine metastases.

Spine metastases are a common cause of pain in the oncologic patient which can generate functional limitation, in addition to complications derived from spinal cord compression, radicular compression and fractures. A complex approach to these metastases is required due to the risk of permanent sequelae. With the increase in survival rates due to new emerging treatments, the possibilities of presenting vertebral metastases are increasing, therefore, the management of these lesions should be aimed at pain relief and maintenance of ambulation. Radiotherapy has a fundamental role in the management of these lesions, and technological advances in recent years have made it possible to improve the quality and intentionality of the treatments, going from having a palliative intent to proposing treatments that improve local control. In this article, we describe how the stereotactic body radiotherapy (SBRT) technique, in selected patients, can improve local control and its value in oligometastatic patients and after surgery.

Role of radiotherapy in the management of spine metastases. / Papel de la radioterapia en el manejo de las metástasis vertebrales: últimas novedades.

Spine metastases are a common cause of pain in the oncologic patient which can generate functional limitation, in addition to complications derived from spinal cord compression, radicular compression and fractures. A complex approach to these metastases is required due to the risk of permanent sequelae. With the increase in survival rates due to new emerging treatments, the possibilities of presenting vertebral metastases are increasing, therefore, the management of these lesions should be aimed at pain relief and maintenance of ambulation. Radiotherapy has a fundamental role in the management of these lesions, and technological advances in recent years have made it possible to improve the quality and intentionality of the treatments, going from having a palliative intent to proposing treatments that improve local control. In this article we describe how the stereotactic body radiotherapy (SBRT) technique, in selected patients, can improve local control and its value in oligometastatic patients and after surgery.

Tick-borne pathogens in ticks from urban and suburban areas of north-western Spain: Importance of Ixodes frontalis harbouring zoonotic pathogens.

To identify the questing tick populations in urban and suburban areas from the city of Lugo (NW Spain), ticks were collected monthly by flagging. The presence of Borrelia spp., Rickettsia spp. and Anaplasma phagocytophilum also was determined by polymerase chain reaction (PCR) and sequence analysis. Overall, 342 questing ticks were collected; the tick abundance was higher in suburban (95.9%) than in urban areas (4.1%). Ixodes frontalis was the most abundant (86.5%); 88.5% were larvae, 11.1% nymphs and 0.3% adults. All development stages of I. ricinus (7.3%) and adults of Rhipicephalus sanguineus sensu lato (5.8%) and Dermacentor reticulatus (0.3%) were found. Rickettsia spp. (31.9%) was more prevalent than Borrelia spp. (2.7%); no ticks were positive to A. phagocytophilum. Six Rickettsia species were identified (R. slovaca, R. monacensis, R. massiliae, R. raoultii, R. sibirica subsp. mongolitimonae and R. aeschielmanii); Candidatus Rickettsia rioja and two novel Rickettsia species also were detected. In addition, Borrelia turdi (1.8%) and B. valaisiana (0.9%) were identified in Ixodes ticks. This is the first report of R. slovaca in R. sanguineus s.l. and of R. monacensis, R. raoultii, R. slovaca, R. sibirica subsp. mongolitimonae and Ca. R. rioja in I. frontalis. Since most of the pathogens detected are zoonotic, their presence in these areas may have implications for public health.

Pilot-scale bioconversion of rice and sunflower agro-residues into medicinal mushrooms and laccase enzymes through solid-state fermentation with Ganoderma lucidum.

Solid-state fermentation was evaluated at the pilot-scale for the bioconversion and valorization of rice husks and straw (RSH), or sunflower seed hulls (SSH), into medicinal mushrooms and crude extracts, with laccase activity. The average mushroom yield was 56kg dry weight per ton of agro-residues. Laccase activity in crude aqueous extracts showed its maximum value of 10,927Ukg-1 in RSH (day 10, Exudate phase) and 16,442Ukg-1 in SSH (day 5, Full colonization phase), the activity at the Residual substrate phase being 511Ukg-1 in RSH and 803Ukg-1 in SSH, respectively. Crude extracts obtained with various protocols revealed differences in the extraction yields. Lyophilization followed by storage at 4°C allowed the preservation of laccase activity for more than one month. It is proposed that standard mushroom farms could increase their profits by obtaining laccase as a byproduct during the gaps in mycelium running.

Effectiveness and toxicity of helical tomotherapy for patients with locally recurrent nasopharyngeal carcinoma.

PURPOSE: We assessed therapeutic outcomes of reirradiation with helical tomotherapy (HT) for locoregional recurrent nasopharyngeal carcinoma (LRNPC) patients. METHODS AND MATERIALS: Treatment outcomes were evaluated retrospectively in 17 consecutive LRNPC patients receiving HT between 2006 and 2012. Median age was 57 years and most patients (n = 13) were male. Simultaneous systemic therapy was applied in 5 patients. Initial treatment covered the gross tumor volume with a median dose of 70 Gy (60-81.6 Gy). Reirradiation was confined to the local relapse region with a median dose of 63 Gy (50-70.2 Gy), resulting in a median cumulative dose of 134 Gy (122-148.2 Gy). The median time interval between initial and subsequent treatment was 42 months (11-126). RESULTS: The median follow-up for the entire cohort was 23 and 35 months for survivors. Three patients (18 %) developed both local and distant recurrences and only one patient (6 %) suffered from isolated local recurrence. Two-year actuarial DFS and LC rates were 74 and 82 %, respectively. Two-year OS rate was 79 %. Acute and late grade 2 toxicities were observed in 8 patients (47 %). No patient experienced late grade ≥3 toxicity. Late toxicity included fibrosis of skin, hypoacusia, dysphagia, and xerostomia. Patients with higher Karnofsky performance status scores associated with a lower risk of mortality (HR 0.85, p = 0.015). CONCLUSION: Reirradiation with HT in patients with LRNPC is feasible and yields encouraging results in terms of local control and overall survival with acceptable toxicity.

Outcome and toxicity using helical tomotherapy for craniospinal irradiation in pediatric medulloblastoma.

PURPOSE: The objective of this study is to evaluate the tolerability and outcome of craniospinal irradiation (CSI) with helical tomotherapy (HT) in the treatment of medulloblastoma. METHODS: We evaluated 19 consecutive patients with primary medulloblastoma who were treated with HT from 2007 through 2010. HT regimens to the neuroaxis included: 23.4 Gy at 1.8 Gy/fraction (N = 10), 36 Gy at 1.8 Gy/fraction (N = 7), and 39 Gy bid at 1.3 Gy/fraction (N = 2). The tumor bed received 54-60 Gy. Potential associations between patient, treatment, and toxicity factors and overall survival (OS) were assessed in univariate analyses using the Cox proportional hazards model. Spearman's rank correlation coefficient was used to correlate potential risk factors with the grade of acute toxicity. RESULTS: The median age at diagnosis was 5 years (range 2-14) and the median follow-up for alive patients (N = 14) 40 months (range 10-62). Two- and three-year overall survival was 75 and 68 %, respectively. The most common acute toxicity was hematological (79 %), being grade 2 and grade 3 in 4 (21 %) and 11 (58 %) cases, respectively. No grade ≥2 late toxicities were observed. Higher grades of acute body toxicity were found in older children (P = 0.004). Longer time between diagnosis and radiation therapy was correlated with shorter OS (P = 0.03). In addition, higher grades of acute thrombocytopenia were associated with shorter OS (P = 0.03). CONCLUSIONS: CSI delivered with HT for medulloblastoma is well tolerated with low rates of severe acute toxicity. Further research is necessary to assess late toxicity with a longer follow-up.

Stereotactic ablative radiotherapy delivered by image-guided helical tomotherapy for extracranial oligometastases.

PURPOSE: To investigate the outcomes and risk factors of patients treated with stereotactic ablative radiotherapy (SABR) delivered by image-guided helical tomotherapy (HT) for extracranial oligometastases. METHODS: From August 2006 through July 2011, 42 consecutive patients (median age 69 years [range 16-87]) with oligometastases (≤3) received HT to all known cancer sites (lung, n = 28; liver, n = 12; adrenal, n = 2). Prognostic factors were assessed by Cox's proportional hazards regression analysis. RESULTS: A total of 60 lesions were treated with hypofractionated HT (median dose 39 Gy [range 36-72.5]; median dose per fraction 12 Gy [range 5-20]). Complete or partial response was observed in 40 (54 %) patients. With a median follow-up period of 15 months, 1- and 2-year overall survival (OS) was 84 and 63 %, respectively; and 1- and 2-year local control (LC) was 92 and 86 %, respectively. Four patients had pneumonitis Grade ≥2 and two patients had lower gastrointestinal toxicity Grade ≥2. Only the lack of complete/partial response was associated with higher risk of mortality on univariate (HR = 3.8, P = 0.04) and multivariate (HR = 6.6, P = 0.01) analyses. CONCLUSIONS: SABR delivered by image-guided HT is well tolerated and offers adequate LC with low acute morbidity in patients with extracranial oligometastatic disease. We found that the response to HT was the only predictor for OS.

Agaricus blazei production on non-composted substrates based on sunflower seed hulls and spent oyster mushroom substrate.

Agaricus blazei Murrill is usually cultivated using the same biphasic composting method employed for A. bisporus. Because cultivation of A. blazei on traditional A. bisporus composts poses some disadvantages, non-composted substrates were studied for A. blazei cultivation. Mycelial growth rate and productive performance of A. blazei were evaluated on substrates containing sunflower seed hulls, Pleurotus spp. spent mushroom substrate, or their combination, in the absence or in the presence of different supplements (vermicompost, peat or brewery residues). Substrates were prepared by initially soaking them and then they were sterilized (1 atm for 120 min). In addition, each substrate's degradation was measured after cultivation by obtaining the lignin, cellulose, hemicellulose, organic matter, total fiber, ash, carbon and nitrogen contents before spawn-run and at the end of two flushes of A. blazei. The cultivation of A. blazei on non-composted substrates is possible and with a low rate of contamination when using the spent mushroom substrate as the main component or combined 50:50 with sunflower seed hulls. In addition, the best yields were obtained on those substrates containing spent Pleurotus mushroom substrate with supplements and those mixtures with sunflower seed hulls and vermicompost. These yields were similar to those reported on composted substrates. Substrate changes in composition measured at the end of two flushes indicate that the lignin-hemicellulose fraction was preferentially used and that the substrates exhibiting the best yield showed greater biodegradation of lignin-hemicellulose fraction than the others did.

Response to inhibition of angiotensin-converting enzyme in human immunodeficiency virus-associated nephropathy: a case report.

The most common chronic nephropathy seen with human immunodeficiency virus (HIV) infection is characterized by heavy proteinuria and rapid deterioration of renal function. We here report the findings in an HIV-seropositive patient with nephrotic-range proteinuria and biopsy-proven HIV-associated nephropathy treated with the angiotensin-converting enzyme (ACE) inhibitor, fosinopril. During treatment periods, the patient demonstrated a significant decrement in 24-hour urinary protein excretion without change in renal function. The patient acted as her own control. After discontinuation of the drug, the 24-hour protein excretion deteriorated to pretreatment levels. ACE inhibition has been reported to decrease proteinuria and to have a beneficial influence on the progression of renal failure in diabetic and nondiabetic renal disease. To date, there is no known therapy for HIV-associated nephropathy. Our preliminary results in this patient suggest the need for long-term studies to assess whether this form of therapy can improve proteinuria over longer periods and, at the same time, ameliorate the progressive form of nephropathy seen in selected HIV-seropositive patients.