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.

Encouraging Experience with Image-Guided Pencil Beam Scanning Proton Therapy in Craniopharyngioma-First Case Series From India.

OBJECTIVE: We report our early clinical experience with image-guided, pencil beam scanning proton beam therapy (PBS-PBT) for residual and recurrent craniopharyngioma. METHODS: Between September 2019 and January 2023, 19 consecutive patients with residual or recurrent craniopharyngioma, suitable for radiotherapy and treated with image-guided PBS-PBT were analyzed. We documented detailed dosimetric data, acute toxicities, early outcomes, and imaging response on follow-up magnetic resonance imaging scans. RESULTS: A total of 19 patients (11 males and 8 females) with residual or recurrent craniopharyngioma were treated during the study period. The median age of the cohort was 14 years (range, 3-33 years). The histology of most lesions was the adamantinomatous subtype (95%). The most common clinical presentation (before PBT) and most common endocrine deficit was visual disturbance (79%) and hypocortisolism (74%), respectively. Of the 19 patients, 13 had recurrent craniopharyngioma, and 5 had undergone radiotherapy previously. Five patients (26%) had undergone surgery ≥3 times before proton therapy. The median dose delivered was 54 GyE. The most common acute toxicity was grade 1 alopecia (63%). No patient experienced grade ≥3 acute toxicity. With a median follow-up of 18 months (range, 3-40 months), 12 patients showed shrinkage of the residual tumor and/or cyst, and 4 showed a dramatic cyst reduction at 3-9 months of follow-up. Two patients experienced a reduction in both solid and cystic components, with the remaining experiencing a reduction in the cystic component only. The remaining 8 patients had stable disease on magnetic resonance imaging, with 100% disease control and overall survival. Visual function remained stable after treatment. CONCLUSIONS: Our preliminary experience with modern PBS-PBT and image guidance for craniopharyngioma is encouraging. Proton therapy in our cohort was well tolerated, resulting in limited toxicity and promising early outcomes.

Successful Implementation of Image-Guided Pencil-Beam Scanning Proton Therapy in Medulloblastomas.

Medulloblastoma is the most common malignant brain tumour in children, while much rarer in adults. Although the prognosis and outcomes have greatly improved in the era of modern multidisciplinary management, long-term treatment-induced toxicities are common. Craniospinal irradiation followed by a boost to the primary and metastatic tumour sites forms the backbone of treatment. Proton therapy has been endorsed over conventional photon-based radiotherapy due to its superior dosimetric advantages and subsequently lower incidence and severity of toxicities. We report here our experience from South-East Asia's first proton therapy centre of treating 40 patients with medulloblastoma (38 children and adolescents, 2 adults) who received image-guided, intensity-modulated proton therapy with pencil-beam scanning between 2019 and 2023, with a focus on dosimetry, acute toxicities, and early survival outcomes. All patients could complete the planned course of proton therapy, with mostly mild acute toxicities that were manageable on an outpatient basis. Haematological toxicity was not dose-limiting and did not prolong the overall treatment time. Preliminary data on early outcomes including overall survival and disease-free survival are encouraging, although a longer follow-up and data on long-term toxicities are needed.

Revival of Brock's Operation for Intermediary Palliation of Fallot's Tetralogy in Children Anatomically Unsuitable for One-Stage Total Correction of the Anomaly: Interim Results of Two Cases.

One-stage total correction is known to be anatomically unsuitable for correcting tetralogy of fallot (TOF) in a certain proportion of children. Surgeons are thus faced with dilemmas regarding which preliminary operation for the anomaly to do first. Brock's primary postulation suggests that pulmonary trunk and annulus enlargement leading to the correction of the outflow obstruction will favor the subsequent total correction. In line with this, the current article presents two patients who were 6 months and 5 years old. The first patient underwent primary Brock's operation while the second patient had a blocked modified Blalock-Taussig's shunt (MBTS) done off-pump. Following the discontinuation of anti-platelet medications, the MBTS blocked and the patient was subsequently considered for secondary Brock's operation. The outcome of both procedures involved the patients' discharge with uneventful hospital stays and regular follow-ups at specified intervals. Thus, Brock's operation is an excellent preliminary palliative procedure for one-stage total correction of TOF. There is a need to revive 'Brock's procedure' for patients with TOF and poor pulmonary artery anatomy as the procedure of choice. The first direct intra-cardiac operation aimed at directly addressing the pathological anatomy on its Diamond Jubilee Year.

Mid-Term Outlook Following Modified Senning's Operation for the Correction of Transposition of the Great Arteries: A Case Series and Review of Literature.

At the time of writing, two patients who underwent modified Senning's operation (MSO) for the treatment of transposition of great arteries (TGAs) were followed up. At the time of surgery, the patients were three months and 15 years old, respectively. The duration of the follow-up was three years, during which there was a good prognosis, and hence no further invasive treatments were required. There was normal functioning of the right ventricle (RV) in both patients, with the exception of a minor baffle leak in the three-month-old patient. At the annual three-year follow-up, the tricuspid regurgitation (systemic atrioventricular valve) status was moderate in the three-year-old child and mild in the 18-year-old girl. Both patients maintained sinus rhythm and are assigned classification as New York Heart Association (NYHA) Classes I and II. This study aims to assess the midterm outlook after MSO in order to identify and manage future long-term complications. Our report shows a positive outcome in terms of survival and functional activities among children with d-TGA; however, there is a strong need for future research to evaluate the prognosis in the long term (LT) and to assess the functioning of RV.

Robustly optimized hybrid intensity-modulated proton therapy for craniospinal irradiation.

Aim: The aim of the study was to investigate the hybrid robust optimization planning approach in intensity-modulated proton therapy (IMPT) of craniospinal irradiation (CSI). Subjects and Methods: Five IMPT-based adult CSI plans in supine position were created using Raystation treatment planning system (TPS) modelled for Proteus plus proton therapy system. A hybrid planning strategy was implemented, where clinical target volume was robustly optimized (RB) for set up uncertainties and planning target volume was optimized for target coverage using minimax algorithm in the TPS. Beam angle selection, optimization, and dose calculation approach were carefully performed to ensure optimum organ at risk (OAR) sparing, even with potential setup and range errors. The complementary dose gradients in junctions were generated using spot assignment and RB technique. Dosimetric outcomes in both nominal plan and the 16 error scenarios (±3 mm setup and 3.5% range) were analyzed using standard dose volume histogram. Results: This planning approach resulted in a homogeneous dose distribution in the target volume of CSI, including the junction regions, by explicitly reducing number of robust optimization scenarios. The proposed technique was also able to achieve excellent coverage to cribriform plate with lower lens doses and minimal dose to other OARs. Target and OAR doses in the nominal plans as well as in the worst case scenarios with setup and range errors were able to meet the predefined clinical goal. Conclusions: This proposed planning technique is efficient, robust against the uncertainties. It could be adopted in other proton therapy centers.

Current perspective of immunomodulators for lung transplant.

Lung transplantation is an effective treatment option for selected patients suffering from end-stage lung disease. More intensive immunosuppression is enforced after lung transplants owing to a greater risk of rejection than after any other solid organ transplants. The commencing of lung transplantation in the modern era was in 1983 when the Toronto Lung Transplant Group executed the first successful lung transplant. A total of 43,785 lung transplants and 1365 heart-lung transplants have been performed from 1 Jan 1988 until 31 Jan 2021. The aim of this review article is to discuss the existing immunosuppressive strategies and emerging agents to prevent acute and chronic rejection in lung transplantation.

Higher pulmonary vein index on computed angiography and optimum surgical resection ensures smooth postoperative recovery in Fallot's tetralogy: Special emphasis on indices of evaluation and Monocusp preparation.

Tetralogy of Fallot (TOF) is a common cyanotic congenital heart disease. Its surgical correction requires ventricular septal defect (VSD) closure and right ventricular outflow tract obstruction (RVOTO) relief, with transannular patch enlargement (TAPE) of the pulmonary valve. The first successful repair of TOF was reported in 1954 and consisted of closure of the VSD through a large right ventriculotomy, and RVOTO relief with TAPE of the pulmonary valve. To predict the intraoperative requirements and postoperative course of patients with this condition, various evaluation indices are available that can provide a good indication of patient prognosis. We performed this study in a male child (age, 1 year, 9 months; weight 8.5 kgs.) who underwent intracardiac repair for TOF as a primary procedure. We calculated the pulmonary vein index (PVI), McGoon ratio, and Nakata index. The McGoon ratio was 1.97, Nakata index was 539.22 mm2/m2, and PVI was 368.12 mm2/m2. The child had an uneventful post-operative course with no symptoms of low cardiac output syndrome. He was ventilated for 122 h. The length of intensive care unit and hospital stays were 11 and 14 days, respectively. The PVI is a novel indicator offering prognostic indications for pediatric cardiac patients who have undergone surgical correction of TOF.

Hand-Made Polytetrafluoroethylene Tricuspid-Valved Conduit for Surgical Reconstruction of the Right Ventricular Outflow Tract in a Child With Truncus Arteriosus.

Although a new right ventricle outflow can be introduced during pulmonary artery reconstruction, it is a suboptimal option as the valved conduits that mimic the natural right ventricular outflow do not grow, and a surgical conduit replacement cannot be averted. This study reported the implementation of hand-made polytetrafluoroethylene (PTFE) tricuspid-valved conduits to rebuild the right ventricular outflow tract in toddlers with truncus arteriosus and risk factors for earlier conduit explant. Herein, we described a case report of a 9-month-old toddler diagnosed in November 2021 with truncus arteriosus type I with ventricular septal defect (VSD) and severe pulmonary arterial hypertension, who has been successfully discharged 20-days postoperative surgical reconstruction with good bi-ventricular functions. Hand-made PTFE tricuspid-valved conduits are efficient in the reconstruction process of the right ventricular outflow tract in children with truncus arteriosus. The conduits are cheap, easily available, and lack potential sensitization.

Scaling skin and failing heart: the cardio-cutaneous connection.

Ichthyosis refers to a comparatively rare group of skin disorders which may present with associated cardiomyopathy. We report a case of an 11-year-old female child who presented with ichthyosis and associated dilated cardiomyopathy. Genetic testing revealed mutation in the RBCK1 gene. She was successfully managed with heart transplantation. The purpose of the case report is to embark on the association between the skin and heart, the role of desmosomes, and the cutaneous manifestations of life-threatening cardiac disease. Cutaneous manifestations should not be escaped, as some of which could be a marker for sudden cardiac death and appropriate corrective actions can potentially save life.

Heart transplantation for patients with single ventricle physiology.

BACKGROUND: There is a growing population of palliated and unpalliated single ventricle physiology patients for whom heart transplantation is the only treatment option available. There is a paucity of reports of heart transplantation in this challenging and growing subset of patients from our part of the world. The purpose of the article is to briefly review our experience in the subgroup and compare it with the available literature. METHODS: This was a single-institution retrospective observational study of 16 patients with single ventricle physiology who were transplanted between 2016 and 2019 and their outcomes. The study groups were divided into those with ventricular dysfunction (group 1), who fare substantially better than those with normal ventricular function (group 2) whose short-term outcomes were poorer. Worsening cyanosis, poor candidature for completion Fontan procedure due to severe atrioventricular valve regurgitation or pulmonary artery anatomy, protein-losing enteropathy, plastic bronchitis, and worsening systemic venous congestion are indications in those with normal ventricular function. RESULTS: Patients with ventricular dysfunction as the main indication had excellent early survival with no early mortality compared to 40% mortality in patients with normal ventricular function. Patients who survived to leave the hospital had however similar long-term outcomes. Two patients with protein-losing enteropathy resolved completely by one month. Normal ventricular function, pulmonary artery stenting, early Fontan failure (6 months), ascites, and need for desensitization were risk factors for early mortality. After the early acute phase of increased risk, the mortality risk plateaued off. CONCLUSION: Transplantation in patients with single ventricle and ventricular dysfunction can be offered with a good early and late outcome. There is a need to have multi-institutional and multi-disciplinary collaboration along with work in basic sciences to better understand the effects of failed Fontan physiology with normal ventricular function.

Cardiac transplantation for cardiomyopathy with constrictive pericarditis.

Constrictive pericarditis is a great mimic and has posed a diagnostic dilemma since its first description 300 years ago as "Concretio Cordis." It can mimic restrictive cardiomyopathy, endomyocardial fibrosis, and chronic liver and renal disease. This would perhaps be the first clinical report of constriction in patients undergoing cardiac transplantation. We report two distinct cases with cardiomyopathy requiring cardiac transplantation and the clinical implications of concomitant pericardial constriction. While the first case mimics a natural "cardiac support device," which addresses ventricular remodeling in heart failure by reducing the wall stress, the second case is a case in point against the use of "biological pericardial membrane-like the bovine pericardium," as a pericardial substitute.

Impact of spot positional errors in robustly optimized intensity-modulated proton therapy plan of craniospinal irradiation.

We investigated the influence of random spot positioning errors (SPEs) on dosimetric outcomes of robustly optimized intensity-modulated proton therapy (RB-IMPT) plans in craniospinal irradiation (CSI). Six patients with CSI treated using the RB-IMPT technique were selected. An in-house MATLAB code was used to simulate a random SPE of 1 mm in positive, negative, and both directions for 25%, 50%, and 75% of the total spot positions in the nominal plan. The percentage dose variation (ΔD%) in the six nominal and 54 error-introduced plans was evaluated using standard dose-volume indices, line dose difference, and 3D gamma analysis method. The introduction of a random SPE of 1 mm resulted in a reduction in D99%, D98%, and D95% of both CTVs and PTVs by < 2% compared with the corresponding nominal plans. However, this leads to an increase in D1% of the lens by up to 16.9%. The line dose in the junction region showed ΔD% < 2% for the brain and upper spine and < 4% for the upper and lower spine. The 3D gamma values for 3% at 3 mm and 2% at 2 mm were above 99% and 95%, respectively, in all 54 error-introduced plans. The worst decrease in gamma values was observed for 1% at 1 mm, with values ranging from 64 to 78% for all types of SPE. The RB-IMPT plan for CSI investigated in this study is robust enough for target coverage, even if there are random SPEs of 1 mm. However, this leads to an increase in the dose to the critical organ located close to the target.

Endovascular coiling in the treatment of patients with renal artery aneurysms.

Endovascular coiling is a percutaneous endovascular technique used in the management of arterial aneurysms with high success rates and minimal associated morbidity. We present a series of three patients with incidental renal artery aneurysms treated successfully with endovascular coiling, despite comorbidities. One patient had an aneurysm associated with a solitary kidney. The decision to use this technique becomes critical when the aneurysm involves a single functioning kidney. Each renal artery aneurysm was successfully coiled by combining vascular and neurointerventional techniques. The results from the present case series also highlight the challenges faced in therapeutic decision-making in complex situations with limited error margins.

Dosimetric impact of random spot positioning errors in intensity modulated proton therapy plans of small and large volume tumors.

OBJECTIVE: To study dosimetric impact of random spot positioning errors on the clinical pencil beam scanning proton therapy plans. METHODS AND MATERIALS: IMPT plans of 10 patients who underwent proton therapy for tumors in brain or pelvic regions representing small and large volumes, respectively, were included in the study. Spot positioning errors of 1 mm, -1 mm or ±1 mm were introduced in these clinical plans by modifying the geometrical co-ordinates of proton spots using a script in the MATLAB programming environment. Positioning errors were simulated to certain numbers of (20%, 40%, 60%, 80%) randomly chosen spots in each layer of these treatment plans. Treatment plans with simulated errors were then imported back to the Raystation (Version 7) treatment planning system and the resultant dose distribution was calculated using Monte-Carlo dose calculation algorithm.Dosimetric plan evaluation parameters for target and critical organs of nominal treatment plans delivered for clinical treatments were compared with that of positioning error simulated treatment plans. For targets, D95% and D2% were used for the analysis. Dose received by optic nerve, chiasm, brainstem, rectum, sigmoid, and bowel were analyzed using relevant plan evaluation parameters depending on the critical structure. In case of intracranial lesions, the dose received by 0.03 cm3 volume (D0.03 cm3) was analyzed for optic nerve, chiasm and brainstem. In rectum, the volume of it receiving a dose of 65 Gy(RBE) (V65) and 40 Gy(RBE) (V40) were compared between the nominal and error introduced plans. Similarly, V65 and V63 were analyzed for Sigmoid and V50 and V15 were analyzed for bowel. RESULTS: The maximum dose variation in PTV D95% (1.88 %) was observed in a brain plan in which the target volume was the smallest (2.7 cm3) among all 10 plans included in the study. This variation in D95% drops down to 0.3% for a sacral chordoma plan in which the PTV volume is significantly higher at 672 cm3. The maximum difference in OARs in terms of absolute dose (D0.03 cm3) was found in left optic nerve (9.81%) and the minimum difference was observed in brainstem (2.48%). Overall, the magnitude of dose errors in chordoma plans were less significant in comparison to brain plans. CONCLUSION: The dosimetric impact of different error scenarios in spot positioning becomes more prominent for treatment plans involving smaller target volume compared to plans involving larger target volumes. ADVANCES IN KNOWLEDGE: Provides information on the dosimetric impact of various possible spot positioning errors and its dependence on the tumor volume in intensity modulated proton therapy.

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.

Burns in Diabetes Mellitus Patients among Indian Population: Does it Differ from the Rest?

BACKGROUND: Burn injuries in adults can be complicated due to various underlying factors. Of all the co-morbidities complicating wound healing and prognosis of the patient post burn injury, diabetes mellitus is the most common in India. We therefore aimed to explore the epidemiology, interventions, complications, and outcomes in diabetic patients with burn injury. AIM: To analyze demographic characteristics, clinical and microbiological profile and outcome of diabetic burns patients in comparison with nondiabetic burns patients. MATERIALS AND METHODS: This study was a retrospective analysis of diabetic and nondiabetic burns patients admitted to Apollo speciality clinics, Vanagaram, a tertiary care facility in Chennai over a period of 3 years. Data such as age, gender, type and degree of burns, percentage of burns and length of stay, mortality rate, infection rate, type of infections, surgical procedures, and medical complications were analyzed in comparison with nondiabetic burns patients. RESULTS: Among ninety-four burns patients admitted to our hospital over a period of 3 years, 18 patients (19%) were diabetics and 76 patients (81%) were nondiabetics. Mean age of diabetics was 58.2 years (SD-17.1) and nondiabetics was 36.3 years (SD-16.4). Surgical intervention with split skin graft was performed in 50% of diabetics and 48.7% of nondiabetics. Average length of stay of diabetics was 12.6 days and nondiabetics was 16.2 days (p value: 0.334). Diabetic patients with burns were noted to have higher rate of infection (67% vs 61.8%, p value: 0.803) and mortality (44% vs 35.5%, p value: 0.482). CONCLUSION: The clinical course is different between diabetic and nondiabetic patients with burns injury. Although length of stay and surgical interventions were not significantly different, diabetes as a comorbidity appears to increase the risk of infections and mortality in patients with burns. HOW TO CITE THIS ARTICLE: Vadala R, Princess I, Ebenezer R, Ramakrishnan N, Krishnan G. Burns in Diabetes Mellitus Patients among Indian Population: Does it Differ from the Rest? Indian J Crit Care Med 2020;24(1):11-16.