Critical Appraisal of Paediatric Embryonal Cancers Treated with Image-guided Intensity-modulated Proton Therapy.

AIM: To carry out a comprehensive critical appraisal of image-guided intensity-modulated proton therapy practice for craniospinal irradiation (CSI). MATERIALS AND METHODS: An image-guided intensity-modulated proton therapy database of 45 consecutive paediatric patients with central nervous system embryonal malignancies treated between January 2019 and April 2022 were critically appraised for demography, diagnosis, treatment planning strategy and treatment delivery accuracy. RESULTS: Most patients (median age: 7.5 years; male:female ratio: 34:11) had medulloblastoma (56%), followed by recurrent ependymoma (19%), pinealoblastoma (5%), germ cell (5%) and others (15%). The dose to the planning target volume-craniospinal (PTV-CS; length 39.06-79.59 cm) varied from 21 to 35 GyRBE, whereas the combined median dose to craniospinal and boost was 54 GyRBE. In all patients, the 95% isodose line covered the cribriform plate completely and optic nerves mostly, with a median V95% of 100% and 82.96%, keeping Dmax to the lens <3.9 GyRBE. In skeletally immature patients (88.38%), the anterior vertebral body was completely covered in 18.18% and underdosed in 70.15% of the cases, resulting in a median Dmean of 10.11 GyRBE to the oesophagus. Lateral spine coverage was maintained on the edges of the vertebral body in 52.2%, whereas it extended beyond in 48.8%. The median V98% for clinical target volumes and V95% for PTVs of the brain, spine and craniospinal were >97%, with excellent conformity (0.89) and homogeneity (0.07) indices for PTV-CS. All neurological organs at risk received a median Dmax ranging from 36 to 44 GyRBE from the combined CSI and boost regimens. Analysis of patient-specific quality assurance results revealed that 545 (97.67%) planar dosage verification had gamma (3% at 3 mm) values >95%. The online patient set-up verification showed translational and rotational deviation within 2 mm and 0.5° in 88-94% and 97% of the cases. Systematic and random error were within 0.90 mm and 1.71 mm in translation and 0.1° and 0.2° in rotation. CONCLUSION: A change in practice pattern was observed. The findings from our comprehensive critical appraisal add to the growing library of CSI practice and may serve as a reference for inter-institutional comparison.

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. 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.

A novel hybrid 3D dose reconstruction approach for pre-treatment verification of intensity modulated proton therapy plans.

AIM: A novel hybrid three-dimensional (3D) dose reconstruction method, based on planar dose measured at a single shallower depth, was developed for use as patient-specific quality assurance (PSQA) of intensity modulated proton therapy (IMPT) plans. The accuracy, robustness and sensitivity of the presented method were validated for multiple IMPT plans of varying complexities. METHODS AND MATERIALS: An in-house MATLAB program was developed to reconstruct 3D dose distribution from the planar dose (GyRBE) measured at 3 g cm-2 depth in water or solid phantom using a MatriXX PT ion chamber array. The presented method was validated extensively for 11 single-field optimization (SFO) and multi-field optimization (MFO) plans on Proteus Plus. A total of 47 reconstructed planar doses at different depths were compared against the corresponding RayStation treatment planning system (TPS) and MatriXX PT measurement using a gamma passing rate (γ%) evaluated for 3%/3 mm. The robustness of the reconstruction method with respect to depth, energy layers, field dimensions and complexities in the spot intensity map (SIM) were analysed and compared against the standard PSQA. The sensitivity of the reconstruction method was tested for plans with intentional errors. RESULTS: The presented reconstruction method showed excellent agreement (mean γ% > 98%) and robustness with both TPS-calculated and measured dose planes at all depths (2.97-30 g cm-2), energy layers (82.1-225.5 MeV), field dimensions, target volume (17.7-1000 cm3) and SIMs from both SFO and MFO plans. In comparison to the overall mean ± SD γ% from standard PSQA, the reconstruction method showed reductions in mean γ% within 1% for both standard cubes and clinical plans. The reconstruction method was sensitive enough to detect intentional spot positional errors in a selected energy layer of a plan. CONCLUSION: The presented hybrid reconstruction method is sufficiently accurate, robust and sensitive to estimate planar dose at any user-defined depth. It simplifies the measurement setup and eliminates multiple depth measurements.

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.

Characterization and Performance Evaluation of the First-Proton Therapy Facility in India.

PURPOSE: The purpose of this study is to evaluate the performance characteristic of volumetric image-guided dedicated-nozzle pencil beam-scanning proton therapy (PT) system. MATERIALS AND METHODS: PT system was characterized for electromechanical, image quality, and registration accuracy. Proton beam of 70.2-226.2 MeV was characterized for short- and long-term reproducibility in integrated depth dose; spot profile characteristics at different air gap and gantry angle; positioning accuracy of single and pattern of spot; dose linearity, reproducibility and consistency. All measurements were carried out using various X-ray and proton-beam specific detectors following standard protocols. RESULTS: All electro-mechanical, imaging, and safety parameters performed well within the specified tolerance limit. The image registration errors along three translation and three rotational axes were ≤0.5 mm and ≤0.2° for both point-based and intensity-based auto-registration. Distal range (R90) and distal dose fall-off (DDF) of 70.2-226.2 MeV proton beams were within 1 mm of calculated values based on the international commission on radiation units and measurements 49 and 0.0156× R90, respectively. The R90 and DDF were reproducible within a standard deviation of 0.05 g/cm2 during the first 8 months. Dose were linear from 18.5 (0.011 MU/spot) to 8405 (5 MU/spot) MU, reproducible within 0.5% in 5 consecutive days and consistent within 0.8% for full rotation. The cGy/MU for 70.2-226.2MeV was consistent within 0.5%. In-air X(Y) spot-sigma at isocenter varies from 2.96 (3.00) mm to 6.68 (6.52) mm for 70.2-226.2 MeV. Maximum variation of spot-sigma with air-gap of ±20 cm was ±0.36 mm (5.28%) and ±0.82 mm (±12.5%) along X- and Y-direction and 3.56% for full rotation. Relative spot positions were accurate within ±0.6 mm. The planned and delivered spot pattern of known complex geometry agreed with (γ%≤1) for 1% @ 1 mm >98% for representative five-proton energies at four gantry angle. CONCLUSION: The PT-system performed well within the expected accuracy level and consistent over a period of 8 months. The methodology and data presented here may help upcoming modern PT center during their crucial phase of commissioning.

Comparison of Epidemiology and Outcomes in Neuro-Oncology Between the East and the West: Challenges and Opportunities.

Although neoplasms of the brain and central nervous system (CNS) are relatively uncommon, comprising only 1-2% of the overall cancer burden, they represent a substantial source of morbidity and mortality worldwide. The age-adjusted annual incidence of CNS tumours is reportedly low; however, there is substantial global variability in its incidence, with nearly a five-fold difference between regions with the highest rates in developed countries in the West and those with the lowest rates in developing countries in South-East Asia, including India, possibly attributable to key differences in environmental factors, genetic susceptibilities and cultural practices, as well as resource constraints in low-middle income countries precluding precise ascertainment and accurate diagnosis. The burden of CNS tumours is further compounded by the fact that they require highly specialised and skilled multidisciplinary care, including access to modern neuroimaging, neurosurgery, neuropathology and molecular biology, radiotherapy, chemotherapy and rehabilitation services, which may not be widely available in an integrated manner in large parts of the world with a large variation in clinical pathways, non-uniformity of care and resultant heterogeneity in clinical outcomes. CNS tumours encompass a heterogeneous spectrum of histopathological entities with differences in presentation, distinct molecular/genetic alterations, diverse biological behaviour and varying clinical outcomes. Survival is highly dependent on histology, grade and molecular biology, but varies widely across continents, even for the same tumour type and grade. In general, survival is higher in children with primary brain tumours than in adults, largely due to the differences in histological distribution across age groups. However, there is widespread variability, with 5-year survival for paediatric brain tumours being <40% in some low-middle income countries compared with 70-80% in the developed world. This review compares the descriptive epidemiology and clinical outcomes of primary brain tumours between the East and the West that pose unique challenges but also provide new opportunities in contemporary neuro-oncological practice.

Rechallenge temozolomide in glioma: A case series from India.

INTRODUCTION: Temozolomide (TMZ) is an integral part of upfront treatment of high-grade gliomas. It is administered postsurgery as concurrent therapy with radiation and subsequently as adjuvant chemotherapy for 6-12 cycles. It is unknown whether rechallenge of salvage TMZ in previously treated high-grade glioma has any efficacy. MATERIAL AND METHODS: Patients treated with salvage rechallenged TMZ between January 2015 and August 2016 were included for this retrospective analysis. SPSS version 20 was used for this analysis. Time to event analysis was performed using the Kaplan-Meier method. Progression-free survival (PFS) and overall survival (OS) were estimated. The maximum grade of toxicity was noted in accordance with CTCAE version 4.02. RESULTS: A total of 23 patients were selected for analysis with the median age being 43 years (range: 26-69 years). The tumor histopathology at baseline was astrocytoma Grade 2 in 1 patient, oligodendroglioma Grade 2 in 3 patients, anaplastic astrocytoma in 7 patients, anaplastic oligodendroglioma in 2 patients, and glioblastoma in 10 patients. All of them had previously received TMZ. The median numbers of previous TMZ cycles received were 6 (4-18). The median time to failure postlast treatment was 24 months (5-72 months). The median number of cycles of rechallenged salvage TMZ administered was 6 cycles (range: 1-18). Grade 3-4 myelosuppression was seen in 3 patients (13.4%). The median PFS was 459 days (95% confidence interval: 212.1-705.9). The median OS was 25 months. Six-month OS and 1-year OS were 81.4% and 75.1%, respectively. CONCLUSION: Rechallenge with TMZ in recurrent glioma that had previously responded to TMZ is associated with improvement in PFS and OS and has a sufficiently long disease-free interval.

Reduced Protein Expression of the Na+/Ca2++K+-Exchanger (SLC24A4) in Apical Plasma Membranes of Maturation Ameloblasts of Fluorotic Mice.

Exposure of forming enamel to fluoride results into formation of hypomineralized enamel. We tested whether enamel hypomineralization was caused by lower expression of the NCKX4/SLC24A4 Ca2+-transporter by ameloblasts. Three commercial antibodies against NCKX4 were tested on enamel organs of wild-type and Nckx4-null mice, one of which (a mouse monoclonal) was specific. This antibody gave a prominent staining of the apical plasma membranes of maturation ameloblasts, starting at early maturation. The layer of immuno-positive ameloblasts contained narrow gaps without immunostaining or with reduced staining. In fluorotic mouse incisors, the quantity of NCKX4 protein in ameloblasts as assessed by western blotting was not different from that in non-fluorotic ameloblasts. However, immunostaining of the apical plasma membranes of fluorotic ameloblasts was strongly reduced or absent suggesting that trafficking of NCKX4 to the apical membrane was strongly reduced. Exposure to fluoride may reduce NCKX4-mediated transport of Ca2+ by maturation stage ameloblasts which delays ameloblast modulation and reduces enamel mineralization.

A case series of salvage CCNU in high-grade glioma who have previously received temozolomide from a tertiary care institute in Mumbai.

INTRODUCTION: In our center, we routinely use CCNU (Lomustine) as salvage treatment in high-grade glioma patients who cannot afford bevacizumab. This exploratory analysis was done to report the efficacy and toxicity associated with this regimen. METHODS: Patients who were treated with salvage CCNU (postexposure to temozolomide) between January 2015 and August 2016 were included for this retrospective analysis. SPSS version 16 was used for this analysis. Time-to-event analysis was performed using the Kaplan-Meier method. Progression-free survival (PFS) and overall survival (OS) were estimated. The maximum grade of toxicity during salvage CCNU was noted in accordance with CTCAE version 4.02. RESULTS: In the stipulated period, 16 patients were selected for the analysis. The median age of patients was 43 years (range 15-63 years), and 12 (80.0%) patients were males. The Eastern Cooperative Oncology Group performance status was 0-1 in 11 patients (73.3%) and 2-4 in 4 patients (26.7%). The tumor histopathology at diagnosis was glioblastoma in ten patients (66.6%), anaplastic astrocytoma in four (26.7%) patients, and anaplastic oligodendroglioma in one patient (6.7%). Grade 3-4 myelosuppression was seen in five patients (33.3%). The median PFS and OS were 192 days (95% confidence interval [CI]: 156.0-227.5 days) and 282 days (95% CI: 190.9-373.1 days), respectively. CONCLUSION: CCNU is associated with modest treatment outcomes in recurrent/relapsed high-grade gliomas. The high rate of myelosuppression is a concern. Urgent efforts are required to improve upon these results.

Ameloblast Modulation and Transport of Cl⁻, Na⁺, and K⁺ during Amelogenesis.

Ameloblasts express transmembrane proteins for transport of mineral ions and regulation of pH in the enamel space. Two major transporters recently identified in ameloblasts are the Na(+)K(+)-dependent calcium transporter NCKX4 and the Na(+)-dependent HPO4 (2-) (Pi) cotransporter NaPi-2b. To regulate pH, ameloblasts express anion exchanger 2 (Ae2a,b), chloride channel Cftr, and amelogenins that can bind protons. Exposure to fluoride or null mutation of Cftr, Ae2a,b, or Amelx each results in formation of hypomineralized enamel. We hypothesized that enamel hypomineralization associated with disturbed pH regulation results from reduced ion transport by NCKX4 and NaPi-2b. This was tested by correlation analyses among the levels of Ca, Pi, Cl, Na, and K in forming enamel of mice with null mutation of Cftr, Ae2a,b, and Amelx, according to quantitative x-ray electron probe microanalysis. Immunohistochemistry, polymerase chain reaction analysis, and Western blotting confirmed the presence of apical NaPi-2b and Nckx4 in maturation-stage ameloblasts. In wild-type mice, K levels in enamel were negatively correlated with Ca and Cl but less negatively or even positively in fluorotic enamel. Na did not correlate with P or Ca in enamel of wild-type mice but showed strong positive correlation in fluorotic and nonfluorotic Ae2a,b- and Cftr-null enamel. In hypomineralizing enamel of all models tested, 1) Cl(-) was strongly reduced; 2) K(+) and Na(+) accumulated (Na(+) not in Amelx-null enamel); and 3) modulation was delayed or blocked. These results suggest that a Na(+)K(+)-dependent calcium transporter (likely NCKX4) and a Na(+)-dependent Pi transporter (potentially NaPi-2b) located in ruffle-ended ameloblasts operate in a coordinated way with the pH-regulating machinery to transport Ca(2+), Pi, and bicarbonate into maturation-stage enamel. Acidification and/or associated physicochemical/electrochemical changes in ion levels in enamel fluid near the apical ameloblast membrane may reduce the transport activity of mineral transporters, which results in hypomineralization.

Slc26a3/Dra and Slc26a6 in Murine Ameloblasts.

Formation of apatite crystals during enamel development generates protons. To sustain mineral accretion, maturation ameloblasts need to buffer these protons. The presence of cytosolic carbonic anhydrases, the basolateral Na(+) bicarbonate cotransporter Nbce1, and the basolateral anion exchanger Ae2a,b in maturation ameloblasts suggests that these cells secrete bicarbonates into the forming enamel, but it is unknown by which mechanism. Solute carrier (Slc) family 26A encodes different anion exchangers that exchange Cl(-)/HCO3 (-), including Slc26a3/Dra, Slc26a6/Pat-1, and Slc26a4/pendrin. Previously, we showed that pendrin is expressed in ameloblasts but is not critical for enamel formation. In this study, we tested the hypothesis that maturation ameloblasts express Dra and Slc26a6 to secrete bicarbonate into the enamel space in exchange for Cl(-). Real-time polymerase chain reaction detected mRNA transcripts for Dra and Slc26a6 in mouse incisor enamel organs, and Western blotting confirmed their translation into protein. Both isoforms were immunolocalized in ameloblasts, principally at maturation stage. Mice with null mutation of either Dra or Slc26a6 had a normal dental or skeletal phenotype without changes in mineral density, as measured by micro-computed tomography. In enamel organs of Slc26a6-null mice, Dra and pendrin protein levels were both elevated by 52% and 55%, respectively. The amount of Slc26a6 protein was unchanged in enamel organs of Ae2a,b- and Cftr-null mice but reduced in Dra-null mice by 36%. Our data show that ameloblasts express Dra, pendrin, or Slc26a6 but each of these separately is not critical for formation of dental enamel. The data suggest that in ameloblasts, Slc26a isoforms can functionally compensate for one another.

NBCe1 (SLC4A4) a potential pH regulator in enamel organ cells during enamel development in the mouse.

During the formation of dental enamel, maturation-stage ameloblasts express ion-transporting transmembrane proteins. The SLC4 family of ion-transporters regulates intra- and extracellular pH in eukaryotic cells by cotransporting HCO3 (-) with Na(+). Mutation in SLC4A4 (coding for the sodium-bicarbonate cotransporter NBCe1) induces developmental defects in human and murine enamel. We have hypothesized that NBCe1 in dental epithelium is engaged in neutralizing protons released during crystal formation in the enamel space. We immunolocalized NBCe1 protein in wild-type dental epithelium and examined the effect of the NBCe1-null mutation on enamel formation in mice. Ameloblasts expressed gene transcripts for NBCe1 isoforms B/D/C/E. In wild-type mice, weak to moderate immunostaining for NBCe1 with antibodies that recognized isoforms A/B/D/E and isoform C was seen in ameloblasts at the secretory stage, with no or low staining in the early maturation stage but moderate to high staining in the late maturation stage. The papillary layer showed the opposite pattern being immunostained prominently at the early maturation stage but with gradually less staining at the mid- and late maturation stages. In NBCe1 (-/-) mice, the ameloblasts were disorganized, the enamel being thin and severely hypomineralized. Enamel organs of CFTR (-/-) and AE2a,b (-/-) mice (CFTR and AE2 are believed to be pH regulators in ameloblasts) contained higher levels of NBCe1 protein than wild-type mice. Thus, the expression of NBCe1 in ameloblasts and the papillary layer cell depends on the developmental stage and possibly responds to pH changes.

SU-E-T-442: Assessing Vertex Beam with its Dosimetric Relevance for Intracranial Tumours: A Computational Exploration.

PURPOSE: To assess the selection of the minimal vertex beam angle for the avoidance of organs at risk (OARs) in radiotherapy planning of brain tumors. METHODS: Seventy patients with intracranial tumors were studied. Three field conformal plans with co-planar or non co-planar beam arrangements with an anterior vertex beam were used. Two methods were studied for determining the vertex angle for avoidance of eye as organ at risk. In the standard technique, the beam's eye view (BEV) was used to determine need of vertex beam. For the vertex beam, the angle was approximated to avoid eyes. In the second method, the angle from the baseplate to the posterior surface of the head and the angle from the posterior surface of the head to the inferior-most extent of the head were measured from sagital view. The minimum vertex angle required was calculated as the complement of the sum of these angles. The dose volume histogram parameters were maintained. RESULTS: Depending on the spatial location of the planning target volume with reference to the eyes, patients were classified into 4 types: no overlap; overlap with eye anteriorly; overlap with eye posteriorly, overlap with eye anteriorly and posteriorly. No additional angulation, positive vertex and negative vertex angles were needed for type 1, 2 and 3 respectively. The angle subtended by the isocenter to the neck rest apex was the required vertex angle for type 4. Of the 36 type 2, 3 and 4 patients the planned vertex angle was more than the calculated vertex angle by over 5 degrees in 10 patients, and less by over 5 degrees in 4 patients. CONCLUSIONS: A simple method for deriving the minimal vertex beam angle for OAR avoidance in radiotherapy planning of intracranial tumors was described and validated.

Estrogen, progesterone and HER2 receptor expression in breast tumors of patients, and their usage of HER2-targeted therapy, in a tertiary care centre in India.

BACKGROUND: This study was undertaken to document the pattern of expression of estrogen (ER), progesterone (PR) and human epidermal growth factor receptor-2 (HER2) and the usage of HER2-targeted therapy in a large tertiary care hospital in India in the year 2008. MATERIALS AND METHODS: The histopathology reports of all breast cancer patients registered in the hospital in 2008 were extracted from the electronic medical record system. All the cases were immunohistochemically evaluated for estrogen and progesterone receptor status (ER and PR), and c-erbB-2 protein (HER2) expression using standard immunoperoxidase method. The use of HER2-targeted therapies was evaluated by extracting relevant information from the database of the hospital pharmacy and case charts of patients enrolled in ongoing approved trials. RESULTS: A total of 2001 new patients of invasive breast cancers with available pathology reports were registered in the hospital in the year 2008. ER and/or PR expression was positive in tumors of 1025 (51.2%) patients. HER2 3+ expression by immunohistochemistry (IHC) was found in 335 (16.7%) and HER2 2+ in 163 (8.1%). The triple negative phenotype was found in 596 (29.8%) patients. An estimated 441 patients were eligible to receive HER2-targeted therapy based on their HER2 status. Of these 38 (8.6%) patients received some form of HER2-targeted therapy; 20 patients (4.5%) as part of ongoing clinical trials and 18 (4.1%) as part of routine care. CONCLUSIONS: The overwhelming majority of patients eligible for HER2-targeted therapy in our institution are unable to receive it because of financial constraints and limited access to health insurance. There is a higher fraction of patients with the triple negative phenotype compared to the Western population.

Electron arc therapy for bilateral chest wall irradiation: treatment planning and dosimetric study.

AIMS: The treatment of patients with synchronous bilateral breast cancer is a challenge. We present a report of dosimetric data of patients with bilateral chest walls as the target treated with electron arc therapy. MATERIALS AND METHODS: Ten consecutive patients who had undergone electron arc therapy to the bilateral chest wall for breast cancer were analysed. After positioning and immobilisation, patients underwent computed tomography scans from the neck to the upper abdomen. Electron arc plans were generated using the PLATO RTS (V1.8.2 Nucletron) treatment planning system. Electron energy was chosen depending upon the depth and thickness of the planning target volume (PTV). For all patients, the arc angle ranged between 80 and 280° (start angle 80°, stop angle 280°). The homogeneity index, coverage index and doses to organs at risk were evaluated. The patient-specific output factor and thermoluminescence dosimetry (TLD) measurements were carried out for all patients. The total planned dose to the PTV was 50Gy/25 fractions/5 weeks. RESULTS: The mean PTV (± standard deviation) was 568.9 (±116)cm(3). The mean PTV coverage was 89 (±5.8)% of the prescribed dose. For the right lung, the mean values of D(1) and D(10) were 46 (±7.6) and 30 (±9)Gy, respectively. For the left lung, the mean values of D(1) and D(10) were 45 (±7) and 27 (±8)Gy, respectively. For the heart, the mean values of D(1), D(5) and D(10) were 21 (±15), 13.5 (±12) and 9 (±9)Gy, respectively. The mean values of TLD at various pre-specified locations on the chest wall surface were 1.84, 1.82, 1.82, 1.89 and 1.78Gy, respectively CONCLUSION: The electron arc technique for treating the bilateral chest wall is a feasible and pragmatic technique. This technique has the twin advantages of adequate coverage of the target volume and sparing of adjacent normal structures. However, compared with other techniques, it needs a firm quality assurance protocol for dosimetry and treatment delivery.

Radiation therapy with implanted cardiac pacemaker devices: a clinical and dosimetric analysis of patients and proposed precautions.

AIMS: To report the radiation planning dosimetric aspects and clinical outcomes of patients with implanted cardiac pacemakers. MATERIALS AND METHODS: Between 2005 and 2009, eight patients with in situ cardiac pacemakers of varied primary site were treated at our hospital. All patients underwent computed tomography-based treatment planning. The target volumes, organs at risk and pacemaker device were all contoured. A treatment plan optimally covering the target area and maximally sparing the pacemaker was generated. All patients were evaluated at baseline, during radiotherapy and after radiotherapy conclusion by a cardiologist as well as pacemaker company personnel. RESULTS: The median age at presentation was 67 (range 53-77) years. There were three men with head and neck primaries, two men with lung primaries and three women with breast primaries. The prescribed dose ranged from 45 to 70 Gy in 25-35 fractions with a daily dose of 1.8-2.0 Gy. Four patients had the pacemaker implanted on the same side as the radiotherapy target. The dose ranges for the minimum, mean and maximum doses to the pacemaker were 0.06-2.0, 0.07-20.6 and 0.14-60.0 Gy, respectively. Radiation therapy was safely delivered in all patients without any untoward effects. At 5 months of median follow-up, all patients were well with no malfunction of the pacemaker. CONCLUSION: A series of eight patients with in situ pacemakers treated with radiotherapy is reported. Radiotherapy can be safely delivered in patients with implanted cardiac pacemakers. However, it mandates a cautious approach in planning and treatment delivery to ensure the least possible dose to the pacemaker. Close liaison with the cardiologist and a pacemaker clinic before, during and after the course of treatment is essential to ensure patient safety.