High-dose salvage re-irradiation in recurrent/progressive adult diffuse gliomas: development of a novel prognostic scoring system.

PURPOSE: Over the past two decades, high-dose salvage re-irradiation (re-RT) has been used increasingly in the multimodality management of adults with recurrent/progressive diffuse glioma. Several factors that determine outcomes following re-RT have been incorporated into prognostic models to guide patient selection. We aimed to develop a novel four-tiered prognostic model incorporating relevant molecular markers from our single-institutional cohort of patients treated with high-dose salvage re-RT for recurrent/progressive diffuse glioma. MATERIAL AND METHODS: Various patient, disease, and treatment-related factors impacting upon survival following salvage re-RT were identified through univariate analysis. Each of these prognostic factors was further subdivided and assigned scores of 0 (low-risk), 1 (intermediate-risk), or 2 (high-risk). Scores from individual prognostic factors were added to derive the cumulative score (ranging from 0 to 16), with increasing scores indicating worsening prognosis. RESULTS: A total of 111 adults with recurrent/progressive diffuse glioma treated with salvage high-dose re-RT were included. We could assign patients into four prognostic subgroups (A=15 patients, score 0-3); (B=50 patients, score 4-7); (C=33 patients, score 8-10); and (D=13 patients, score 11-16) with completely non-overlapping survival curves suggesting the good discriminatory ability. Post-re-RT survival was significantly higher in Group A compared to groups B, C, and D, respectively (stratified log-rank p-value <0.0001). CONCLUSION: There exists a lack of universally acceptable 'standard-of-care' salvage therapy for recurrent/progressive diffuse glioma. A novel four-tiered prognostic scoring system incorporating traditional factors as well as relevant molecular markers is proposed for selecting patients appropriately for high-dose salvage re-RT that warrants validation in a non-overlapping cohort.

High-dose salvage re-irradiation for recurrent/progressive adult diffuse glioma: healing or hurting?

Purpose To report survival outcomes and identify prognostic factors of salvage re-irradiation (re-RT) in recurrent/progressive glioma. Methods Medical records of patients treated with high-dose re-RT as part of multi-modality salvage therapy for recurrence/progression of adult diffuse glioma from 2010 to 2019 were analyzed retrospectively. Results A total of 111 patients developing recurrent/progressive high-grade glioma after adequate upfront treatment at initial diagnosis were included. The first course of radiotherapy (RT) had been delivered to a median dose of 59.4 Gy with an inter-quartile range (IQR) of 54-60 Gy. Median time to recurrence/progression was 4.3 years (IQR = 2.3–7.4 years) while the median time to re-RT was 4.8 years (IQR = 3.6–7.9 years). Re-RT was delivered with intensity-modulated radiation therapy (IMRT) using 1.8 Gy/fraction to a median dose of 54 Gy (IQR = 50.4–55.8 Gy) for a cumulative median equivalent dose in 2-Gy fractions (EQD2) of 104.3 Gy (IQR = 102.6–109.4 Gy). At a median follow-up of 14 months after re-RT, the 1-year Kaplan–Meier estimates of post-re-RT progression-free survival (PFS) and overall survival (OS) were 42.8 and 61.8%, respectively. Univariate analysis identified histological grade at recurrence/progression; histological subtype; disease-free interval (DFI) and time interval between both courses of RT; performance status at re-RT; dose at re-RT and cumulative EQD2; isocitrate dehydrogenase (IDH) mutation; and O6-methyl-guanine DNA methyl transferase (MGMT) gene promoter methylation as significant prognostic factors. Preserved performance status, longer DFI, prolonged time interval between both courses of RT, and presence of IDH mutation were associated with significantly improved PFS on multi-variate analysis. However, only performance status retained independent prognostic significance for OS on multi-variate analysis (AU)

High-dose salvage re-irradiation for recurrent/progressive adult diffuse glioma: healing or hurting?

PURPOSE: To report survival outcomes and identify prognostic factors of salvage re-irradiation (re-RT) in recurrent/progressive glioma. METHODS: Medical records of patients treated with high-dose re-RT as part of multi-modality salvage therapy for recurrence/progression of adult diffuse glioma from 2010 to 2019 were analyzed retrospectively. RESULTS: A total of 111 patients developing recurrent/progressive high-grade glioma after adequate upfront treatment at initial diagnosis were included. The first course of radiotherapy (RT) had been delivered to a median dose of 59.4 Gy with an inter-quartile range (IQR) of 54-60 Gy. Median time to recurrence/progression was 4.3 years (IQR = 2.3-7.4 years) while the median time to re-RT was 4.8 years (IQR = 3.6-7.9 years). Re-RT was delivered with intensity-modulated radiation therapy (IMRT) using 1.8 Gy/fraction to a median dose of 54 Gy (IQR = 50.4-55.8 Gy) for a cumulative median equivalent dose in 2-Gy fractions (EQD2) of 104.3 Gy (IQR = 102.6-109.4 Gy). At a median follow-up of 14 months after re-RT, the 1-year Kaplan-Meier estimates of post-re-RT progression-free survival (PFS) and overall survival (OS) were 42.8 and 61.8%, respectively. Univariate analysis identified histological grade at recurrence/progression; histological subtype; disease-free interval (DFI) and time interval between both courses of RT; performance status at re-RT; dose at re-RT and cumulative EQD2; isocitrate dehydrogenase (IDH) mutation; and O6-methyl-guanine DNA methyl transferase (MGMT) gene promoter methylation as significant prognostic factors. Preserved performance status, longer DFI, prolonged time interval between both courses of RT, and presence of IDH mutation were associated with significantly improved PFS on multi-variate analysis. However, only performance status retained independent prognostic significance for OS on multi-variate analysis. Post-treatment changes were seen in 33 (30%) patients on follow-up imaging, with higher cumulative dose (EQD2 ≥ 104.3 Gy) being associated with increased risk of post-re-RT pseudo-progression. CONCLUSION: This clinical audit reports encouraging survival outcomes and identifies key prognostic factors associated with high-dose salvage re-RT in recurrent/progressive glioma.

Prospective Longitudinal Assessment of Quality of Life and Activities of Daily Living as Patient-Reported Outcome Measures in Recurrent/Progressive Glioma Treated with High-dose Salvage Re-irradiation.

AIMS: To evaluate quality of life (QOL) and activities of daily living (ADL) longitudinally in patients treated with salvage re-irradiation for recurrent/progressive glioma. Secondary end points included post-re-irradiation survival. MATERIALS AND METHODS: Patients with diffuse glioma, aged 18-70 years with preserved performance status and unequivocal evidence of recurrence/progression with a minimum 2-year time interval from index radiation therapy were eligible. QOL was assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core-30 (QLQ-C30) and brain cancer module (BN20). ADL was assessed using a modified Barthel's index. Assessments were carried out longitudinally, first before re-irradiation, at completion of re-irradiation and subsequently periodically on follow-up. Summary scores were calculated from raw scores as per the EORTC scoring manual; higher functional scores and lower symptom scores indicating better QOL. Summary mean scores for the modified Barthel's index were also calculated, with lower scores indicating higher disability. Differences between the summary scores at different time points were tested using the Friedman test. RESULTS: In total, 225 assessments were carried out in 60 patients accrued on the study. A significant improvement in scores was noted for physical function (P < 0.001), emotional function (P = 0.002), cognitive function (P = 0.009) and social functioning (P = 0.047) over time. Role function scores (P = 0.182) and global health status scores (P = 0.074) remained stable. Among symptom scores, fatigue showed a statistically significant improvement over time (P = 0.01), whereas other symptom scores remained largely stable. There was a significant increase in the modified Barthel's index score over time (P = 0.001), suggesting greater functional independence. At a median follow-up of 12.9 months, the 1-year Kaplan-Meier estimates with 95% confidence intervals of post-re-irradiation progression-free survival and overall survival were 45.1% (31.5-58.7%) and 62.2% (49.2-75.2%), respectively. CONCLUSIONS: High-dose salvage re-irradiation in carefully selected patients with recurrent/progressive glioma is associated with stable QOL (preserved functional domains and reduced symptom burden) and improvement in ADL (greater functional independence) over time with encouraging survival outcomes.

Surgical site infection rates in six cities of India: findings of the International Nosocomial Infection Control Consortium (INICC).

BACKGROUND: Surgical site infections are a threat to patient safety. However, in India, data on their rates stratified by surgical procedure are not available. METHODS: From January 2005 to December 2011, the International Nosocomial Infection Control Consortium (INICC) conducted a cohort prospective surveillance study on surgical site infections in 10 hospitals in 6 Indian cities. CDC National Healthcare Safety Network (CDC-NHSN) methods were applied and surgical procedures were classified into 11 types, according to the ninth edition of the International Classification of Diseases. RESULTS: We documented 1189 surgical site infections, associated with 28 340 surgical procedures (4.2%; 95% CI: 4.0-4.4). Surgical site infections rates were compared with INICC and CDC-NHSN reports, respectively: 4.3% for coronary bypass with chest and donor incision (4.5% vs 2.9%); 8.3% for breast surgery (1.7% vs 2.3%); 6.5% for cardiac surgery (5.6% vs 1.3%); 6.0% for exploratory abdominal surgery (4.1% vs 2.0%), among others. CONCLUSIONS: In most types of surgical procedures, surgical site infections rates were higher than those reported by the CDC-NHSN, but similar to INICC. This study is an important advancement towards the knowledge of surgical site infections epidemiology in the participating Indian hospitals that will allow us to introduce targeted interventions.

Intracranial metastasis from a glandular variant of atrial myxoma.

BACKGROUND: Intracranial metastases from atrial myxoma producing symptomatic mass lesions are very rare with only ten examples reported in the literature. We report a patient with multiple metastases from a cardiac myxoma which had an unusual histopathology mimicking an adenocarcinoma. CLINICAL PRESENTATION: A 35 year old man presented with left facio-brachial focal motor seizures unresponsive to antiepileptic drugs and these episodes preceded the symptoms of cardiac myxoma. The seizures worsened a year following resection of the cardiac myxoma. The MRI of the brain revealed multiple lesions of heterogeneous intensity, partly solid and cystic situated in the right fronto-parietal, left temporal and occipital lobes. FINDINGS: Right fronto-parietal craniotomy revealed lesions with haemorrhagic, calcified areas and a large cystic component was decompressed. Histological examination of the lesions in the brain demonstrated prominent glandular differentiation, identical in morphology to the primary cardiac lesion of a glandular variant of atrial myxoma. CONCLUSION: This report highlights the rare presentation of atrial myxoma with intracranial metastases and reviews previously reported examples. This is only the second case report of a glandular variant of atrial myxoma with metastases to the brain. A pathologist, unaware of this unusual variant of primary atrial myxoma, may mistake the intracranial lesion for a metastatic adenocarcinoma.

Hydrocephalus in Paget's disease.

Neurological manifestations in Paget's disease are rare. Hydrocephalus is infrequent, its etiology in Paget's disease being multi-factorial. Surgical and anesthetic procedures may be challenging, requiring special precautions. We describe one such case and discuss these peculiarities. An elderly lady, diagnosed to have Paget's disease presented with features of recent onset dementia, gait disturbances with urinary incontinence. Hydrocephalus secondary to posterior fossa crowding was present. A ventriculo-peritoneal shunt was inserted. Endotracheal intubation proved to be difficult. Modification of the surgical technique was required to ensure a safe procedure. She improved immediately following CSF diversion. Timely CSF diversion yields good results. Certain precautions during anesthesia and surgery can ensure a safe and uneventful peri-operative period.