Impact of Dosimetric Compromises on Early Outcomes of Chordomas and Chondrosarcomas Treated With Image-guided Pencil Beam Scanning Proton Beam Therapy.

Purpose: To critically review the clinical factors, dosimetry, and their correlation with early outcomes in patients with chordomas and chondrosarcomas treated with pencil beam scanning (PBS) proton beam therapy (PBT). Methods and Materials: Consecutive 64 patients diagnosed with chordoma or chondrosarcoma treated at our center were studied. Patient, tumor, and treatment-related factors including dosimetry were captured. Early and late toxicities and early outcomes were evaluated and correlated with clinical and dosimetric factors using standard statistical tools. Results: The median age of patients was 39 years (range, 4-74 years), and most common site was skull base (47%), followed by sacrum (31%) and mobile spine (22%). The median prescription dose to the high-risk clinical target volumes for chordoma and chondrosarcoma was 70.4 cobalt gray equivalent (CGE) and 66 CGE at 2.2 CGE per fraction, respectively. At presentation, 55% presented after a recurrence/progression of which 17% had received previous radiation and 32% had a significant neural compression. At the time of PBT, 25% of patients had suboptimal neural separation. Three-fourths of patients had at least an acceptable target coverage. Although 11% had a tier 1 compromise (gross tumor volume [GTV] D98 < 90%), 14% had a tier 2 compromise (GTVD98 < 59 CGE). With a median follow-up of 27.5 months, 2-year local control and progression-free survival was 86.7% and 81.8% for chordomas and 87.5% and 77.1% for chondrosarcomas, respectively. Residual GTV of >25 cm3 and a tier 2 compromise were associated with inferior local control (hazard ratio [HR], 0.19; P = .019; HR, 0.061; P = .022, respectively) and progression-free survival (HR, 0.128; P = 0.014; HR, 0.194; P =.025, respectively) on multivariate analysis. Despite multiple surgeries, a majority presented with recurrent disease and previous radiations and grade 3 acute and late toxicities were limited and comparable with others in the literature. Conclusions: Despite multiple surgeries, adequate neural separation was challenging to achieve. Severe dosimetric compromise (GTV D98 < 59 CGE) led to inferior early outcomes. Adequate neural separation is key to avoiding dosimetric compromise and achieving optimal local control.

Impact of intensity-modulated proton therapy in reducing radiation-induced lymphopenia in glioma patients.

Background: Current standard management in adult grades 2-4 gliomas includes maximal safe resection followed by adjuvant radiotherapy (RT) and chemotherapy. Radiation-induced lymphopenia (RIL) has been shown to possibly affect treatment outcomes adversely. Proton beam therapy (PBT) may reduce the volume of the normal brain receiving moderate radiation doses, and consequently RIL. Our aim was to evaluate the incidence and severity of RIL during proton beam therapy (PBT). Methods: We identified patients with grades 2-4 glioma treated with PBT at our center between January 2019 and December 2021. We evaluated the incidence and severity of RIL from weekly complete blood count (CBC) data collected during PBT and compared it to the patients who were treated with photon-based RT (XRT) at our center during the same time. Results: The incidence of any degree of lymphopenia (48% in PBT, vs. 81.2% in XRT, P value = .001) and severe lymphopenia (8% in PBT, vs. 24.6% in XRT, P value = .093) were both significantly lesser in patients who received PBT. Severe RIL in patients receiving PBT was seen in only CNS WHO Gr-4 tumors. Mean whole brain V20GyE and V25GyE inversely correlated to nadir ALC and were both significantly lower with PBT. Patients with lymphopenia during PBT showed a trend toward poorer progression-free survival (P = .053) compared to those with maintained lymphocyte counts. Conclusions: Proton therapy seems to have a superior sparing of normal brain to moderate dose radiation than photon-based RT and reduces the incidence of lymphopenia. Glioma patients with lymphopenia possibly have worse outcomes than the ones with maintained lymphocyte counts.

Is tuberculosis epidemic riding upon the waves of COVID-19 pandemic? A time-trend study from South India.

Background: National Tuberculosis Elimination Programme (NTEP) activities have decelerated due to the COVID-19 pandemic. Doubt is raising globally on emerging tuberculosis (TB) epidemic related to COVID-19 pandemic. In this study, we aim to identify the trends in incidence and patterns of TB during the pandemic (2020-2022). Methods: A single-institution retrospective study was conducted. All data including demography, site of involvement, and the time trends of TB cases registered under NTEP between January 2019 and June 2022 at our hospital were retrieved from the prospective register. Statistical analysis was done using SPSS version 20.0. Results: Total 381 cases were registered. The mean age was 43 years (±17). The male: female ratio was 1.2:1. Majority of females (40%) and males (37%) were in the age of 11-30 years and 31-50 years, respectively. The TB cases' frequency in 2019, 2020, 2021, and 2022 (till June) were 38.3% (146), 11.8% (45), 29.4% (112), and 20.5% (78), respectively. The most common site involved was pulmonary (50%) followed by cervical lymph node (19.9%). A significant reduction in TB cases was noted in 2020 during the first wave of COVID-19. The estimated total TB cases in 2022 are similar to pre-COVID-19 year 2019. The ratio of pulmonary versus extrapulmonary TB was 1:1 during 2020. Conclusions: We found a significant reduction of TB cases during the first wave of COVID-19, but cases have started to rise again and yet to reach pre-COVID-19 status in 2022. No definite evidence of TB epidemic in the background of COVID-19 pandemic was found. Young females within 11-30 years were found to be more affected and need to be the main focus of TB preventive efforts. COVID-19 pandemic has affected the ratio between extrapulmonary and pulmonary TB significantly.

Amide proton transfer imaging-arterial spin labeling mismatch: a new imaging biomarker for pilocytic astrocytoma.

We describe the potential utility of Amide Proton Transfer weighted (APTw) Magnetic Resonance Imaging and arterial spin labeling (ASL) in characterizing pilocytic astrocytoma (PA), a type of brain tumor that can be challenging to accurately diagnose and treat. The study included 50 patients with solid or predominantly solid intra-cranial and intra-axial tumors, with 25 patients diagnosed with PA and 25 patients diagnosed with other types of tumors. The study found that the APTw imaging-arterial spin labeling (ASL) mismatch is a new imaging biomarker that could be used to differentiate PA from other types of tumors with a high degree of sensitivity and specificity. The results suggest that APTw imaging and ASL may be useful in characterizing PA, potentially improving diagnosis and treatment planning for this type of brain tumor.

Measuring glioma volumes: A comparison of linear measurement based formulae with the manual image segmentation technique.

CONTEXT: Gliomas are irregular in shape unlike benign brain tumors like meningiomas or schwannomas. Simplifying assumptions about glioma geometry are therefore more likely to lead to wrong calculations of glioma volumes than for other tumors. AIMS: We compared simple linear measurement.based techniques of measuring glioma volume with manual region of interest.based image segmentation and to assess concordance. SETTINGS AND DESIGN: This study was a retrospective radiology archive-based study. SUBJECTS AND METHODS: The volumes of gliomas were measured by two assessors using five different techniques - manual image segmentation and four linear measurement-based formulae, which included the formulae for the volume of a sphere, cylinder, ellipsoid and its simplification v = abc/2. STATISTICAL ANALYSIS USED: Intra-ssessor concordance was evaluated using mean vs. difference. (Bland-Altman) plots and raw agreement indices. Inter-rater agreement was assessed by calculating the intra-class correlation coefficient for each technique. RESULTS: The best inter.rater concordance was for volume measured by manual segmentation. The tumor volumes measured using the formulae for volume of a sphere and cylinder had poor agreement with the planimetric volume and low inter.rater concordance. The formula for volume of an ellipsoid and its simplification had good agreement with the manual planimetric volume and had good inter.rater concordance. However, for larger tumors, the agreement with planimetric volume was poorer. CONCLUSIONS: Manual region of interest-based image segmentation is the standard technique for measuring glioma volumes. For routine clinical use, the simple formula v = abc/2 (or the formula for volume of an ellipsoid) could be used as alternatives.

A facile one pot route for the synthesis of imide tethered peptidomimetics.

A simple and efficient method for the synthesis of N,N'-orthogonally protected imide tethered peptidomimetics is presented. The imide peptidomimetics were synthesized by coupling the in situ generated selenocarboxylate of N(α)-protected amino acids with N(α)-protected amino acid azides in good yields. The protocol was also successfully applied for the synthesis of hybrid tripeptidomimetics bearing both amide and imide functionalities. In addition, coumarinic imide conjugates of amino acids have been accomplished by employing this protocol. The present method provides a convenient and easy access to imide tethered peptidomimetics and is compatible with common protecting groups employed in peptide chemistry.

A retrospective study to correlate breech presentation and enhanced risk of postspinal hypotension during cesarean delivery.

BACKGROUND: Subarachnoid blockade for cesarean section still poses a threat of profound hypotension and can result in unstable maternal and fetal hemodynamics. The correlation of fetal breech and vertex presentation with the occurrence of hypotension under spinal anesthesia is reviewed in this retrospective, double-blind study. PATIENTS AND METHODS: The study was conducted on pregnant females scheduled for a lower segment cesarean section between January 2014 and December 2014. After applying inclusion criteria, 568 patients were recruited in the study out of which 363 had vertex and 184 patients had breech presentation. They were divided into two groups, Group I and Group II. The monitoring and therapeutic data (blood pressure, heart rate, arterial oxygen saturation, and dose of vasopressor/atropine) recovered from automated data analysis were analyzed retrospectively for prevalence of hypotension, bradycardia, and hypotension with bradycardia and nausea ± vomiting. RESULTS: Among Group I, prevalence of hypotension, bradycardia, and hypotension together with bradycardia was 152 (41.83%) patients, eight (2.20%) patients, and seven (1.92%) patients, respectively. In Group II, the prevalence of hypotension, bradycardia, and hypotension with bradycardia was 93 (50.5%) patients, five (2.71%) patients, and six (3.2%) patients, respectively. The difference between the two groups was statistically significant for hypotension. For Group I, 152 patients (41.87%) experienced one, 23 patients (6.33%) experienced two, and three patients (0.82%) experienced three episodes of hypotension. In Group II, 93 (50.5%), 19 (7.89%), and two (1.08%) patients experienced such episodes. The difference was significant with respect of one and two episodes. The prevalence of intraoperative nausea was 11.01% (40 patients) in Group I, whereas 11.41% (21 patients) in Group II. Intraoperative vomiting occurred in 19 patients (5.23%) of Group I and 14 patients (7.60%) of Group II. The height of the block was comparable in both the groups for T6, and the difference was significant in respect to T4 level. CONCLUSION: Incidence of hypotension is more in pregnant females with breech fetal presentation.

Basal ganglia involvement in a child with herpes simplex encephalitis.

Herpes simplex encephalitis (HSE) is a leading cause of sporadic, nonepidemic viral encephalitis in children and adults. We report a very rare case of HSE with involvement of bilateral thalamus, putamen, upper pons and midbrain, with development of extrapyramidal symptoms which responded to corticosteroid therapy. A 15-mth-old female baby admitted with complaint of fever for 5 days and generalised tonic clonic seizure 10 hours before admission. On clinical examination patient was drowsy, temperature was 39.4 degrees C and vitals were stable with signs of increased intracranial tension. There were no signs of meningeal irritation. Patient gradually become unconscious in the next few hours and pupils were constricted bilaterally with development of atonia in all four limbs and neck muscles. Doll's eye phenomenon was absent.