Weight loss and response to chemotherapy in pediatric patients with osteosarcoma.

BACKGROUND: Weight loss and malnutrition are common findings in pediatric oncology patients, but their prognostic significance is controversial. We sought to evaluate the correlation between weight loss and response to neo-adjuvant chemotherapy in pediatric patients with osteosarcoma. PROCEDURE: All medical files of patients treated for osteosarcoma in a single pediatric haemato-oncology center between January 2011 and October 2022 were retrospectively reviewed. RESULTS: Sixty-three patients were suitable for study inclusion. Data on changes in their body weight between the initiation of neo-adjuvant chemotherapy and local therapy (tumor resection) were extracted. Response to chemotherapy was assessed by the percentage of tumor necrosis at the time of surgery. There was a significant direct correlation between a weight loss of 3% and above and good response to chemotherapy as demonstrated by tumor necrosis above 90%. CONCLUSIONS: Low caloric intake may imitate a caloric restriction diet that was proven to improve response to therapy in some oncological diseases. Further prospective trials are needed for the establishment of recommended caloric intake during chemotherapy in pediatric patients with osteosarcoma.

Suggested role for neutrophil extracellular trap formation in Ewing sarcoma immune microenvironment.

Ewing sarcoma (EWS) is a highly aggressive cancer with a survival rate of 70%-80% for patients with localized disease and under 30% for those with metastatic disease. Tumor-infiltrating neutrophils (TIN) can generate extracellular net-like DNA structures known as neutrophil extracellular traps (NETs). However, little is known about the presence and prognostic significance of tumor-infiltrating NETs in EWS. Herein, we investigated 46 patients diagnosed with EWS and treated in the Tel Aviv Medical Center between 2010 and 2021. TINs and NETs were identified in diagnostic biopsies of EWS by immunofluorescence. In addition, NETs were investigated in neutrophils isolated from peripheral blood samples of EWS patients at diagnosis and following neoadjuvant chemotherapy. The relationships between the presence of TINs and NETs, pathological and clinical features, and outcomes were analyzed. Our results demonstrate that TIN and NETs at diagnosis were higher in EWS patients with metastatic disease compared with those with local disease. High NET formation at diagnosis predicted poor response to neoadjuvant chemotherapy, relapse, and death from disease (p < 0.05). NET formation in peripheral blood samples at diagnosis was significantly elevated among patients with EWS compared with pediatric controls and decreased significantly following neoadjuvant chemotherapy. In conclusion, NET formation seems to have a role in the EWS immune microenvironment. Their presence can refine risk stratification, predict chemotherapy resistance and survival, and serve as a therapeutic target in patients with EWS.

Prevalence and management of methotrexate-induced neurotoxicity in pediatric patients with osteosarcoma: a single-center experience.

AIMS: To determine the incidence, clinical presentation, and outcome of methotrexate (MTX) associated neurotoxicity in pediatric patients treated for osteosarcoma, with the aim of identifying possible risk factors and suggesting recommended treatment for these sequelae. MATERIALS AND METHODS: All medical files of patients treated for osteosarcoma in a single pediatric haemato-oncology center between November 2011 and August 2021 were retrospectively reviewed. All patients were treated according to the EURAMOS AOST0331 protocol, using cisplatin, doxorubicin, and high-dose MTX at a dose of 12 g/m2 over 4 h. RESULTS: Seventy-eight patients with osteosarcoma were identified (age range 5 to 23 years, 42 males). Seven patients (9%) sustained neurotoxicity following treatment with high-dose MTX. Manifestations of neurotoxicity included among others, generalized seizures, confusion, encephalopathy, dysarthria, and choreiform movements. All but one episode occurred following two sequential cycles of high-dose MTX. All 7 had subacute toxicity, 5-10 days following MTX administration, and 1 had both acute and subacute toxicity. Brain MRI was performed for all patients and demonstrated typical MRI changes attributed to MTX neurotoxicity in 4 of them. Two patients received aminophylline; one patient received dextromethorphan. Patients with normal MRI imaging resumed MTX therapy without any sequels. No risk factors were found for high-dose MTX-related toxicity occurrence. CONCLUSIONS: The time of risk of neurotoxicity due to high-dose MTX treatment for osteosarcoma is days 5-10 following two sequential treatment cycles. These findings together with treatment options for these adverse effects should be detailed in the therapeutic protocol of MTX use among pediatric patients with osteosarcoma.

Tramadol Treatment for Chemotherapy-induced Mucositis Pain in Children.

Mucositis, a painful and debilitating condition, is a common side effect of chemotherapy. The role of tramadol in the treatment of mucositis in pediatric patients has not yet been determined. In this retrospective study, we evaluate whether tramadol as single agent achieved a reduction of pain intensity among oncologic children admitted for mucositis. In total, 34 of 54 (63%) episodes were treated with tramadol alone and achieved adequate pain relief. Tramadol's side effects were mild and manageable.

Monitoring the propagation of mechanical waves using an optical fiber distributed and dynamic strain sensor based on BOTDA.

We report a Brillouin-based fully distributed and dynamic monitoring of the strain induced by a propagating mechanical wave along a 20 m long composite strip, to which surface a single-mode optical fiber was glued. Employing a simplified version of the Slope-Assisted Brillouin Optical Time Domain Analysis (SA-BOTDA) technique, the whole length of the strip was interrogated every 10 ms (strip sampling rate of 100 Hz) with a spatial resolution of the order of 1m. A dynamic spatially and temporally continuous map of the strain was obtained, whose temporal behavior at four discrete locations was verified against co-located fiber Bragg gratings. With a trade-off among sampling rate, range and signal to noise ratio, kHz sampling rates and hundreds of meters of range can be obtained with resolution down to a few centimeters.

Frequency-domain analysis of dynamically applied strain using sweep-free Brillouin time-domain analyzer and sloped-assisted FBG sensing.

Fast reconstruction of the whole Brillouin gain spectrum is experimentally demonstrated using sweep-free Brillouin optical time-domain analysis (SF-BOTDA). Strain variations with the frequencies up to 400 Hz are spectrally analyzed, achieving strain sensitivity of 1 microstrain per root Hz at a sampling rate of 5.5 kHz and a spatial resolution of 4m. The results favorably compare with fiber Bragg grating sensing.

Fast Brillouin Optical Time Domain Analysis for dynamic sensing.

A new technique for the fast implementation of Brillouin Optical Time Domain Analysis (BOTDA) is proposed and demonstrated, carrying the classical BOTDA method to the dynamic sensing domain. By using a digital signal generator which enables fast switching among 100 scanning frequencies, we demonstrate a truly distributed and dynamic measurement of a 100 m long fiber with a sampling rate of ~10 kHz, limited only by the fiber length and the frequency granularity. With 10 averages the standard deviation of the measured strain was ~5 µÎµ.

Slope-assisted fast distributed sensing in optical fibers with arbitrary Brillouin profile.

We present a novel method, based on stimulated Brillouin scattering (SBS), for the simultaneous distributed measurement of fast strain variations along the entire length of the sensing fiber. A specially synthesized and adaptable probe wave is used to place the Brillouin interaction always on the slope of the local Brillouin gain spectrum, allowing a single pump pulse to sample fast strain variations along the full length of a fiber with an arbitrary distribution of the Brillouin frequency shift. In this early demonstration of the method, strain vibrations of a few hundred Hz are demonstrated, simultaneously measured on two different sections of an 85 m long fiber, having different static Brillouin shifts and with a spatial resolution of 1.5 m.