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Conducting clinical trials is becoming increasingly challenging lately due to spiraling costs, increased time to market, and high failure rates. Patient recruitment and retention is one of the key challenges that impact 90% of the trials directly. While a lot of attention has been given to optimizing patient recruitment, limited progress has been made towards developing comprehensive clinical trial monitoring systems to determine patients at risk and potentially improve patient retention through the right intervention at the right time. Earlier research in patient retention primarily focused on using deterministic frameworks to model the inherently stochastic patient journey process. Existing generative approaches to model temporal data such as TimeGAN or CRBM , face challenges and fail to address key requirements such as personalized generation, variable patient journey, and multi-variate time-series needed to model patient digital twin. In response to these challenges, current research proposes ClinicalGAN to enable patient level generation, effectively creating a patient's digital twin. ClinicalGAN provides capabilities for: (a) patient-level personalized generation by utilizing patient meta-data for conditional generation; (b) dynamic termination prediction to enable pro-active patient monitoring for improved patient retention; (c) multi-variate time-series training to incorporate relationship and dependencies among different tests measures captured during patient journey. The proposed solution is validated on two Alzheimer's clinical trial datasets and the results are benchmarked across multiple dimensions of generation quality. Empirical results demonstrate that the proposed ClinicalGAN outperforms the SOTA approach by 3-4 × on average across all the generation quality metrics. Furthermore, the proposed architecture is shown to outperform predictive methods at the task of drop-off prediction significantly (5-10% MAPE scores).
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Ensayos Clínicos como Asunto , Humanos , Selección de PacienteRESUMEN
Bilateral Wilms tumour (BWT) is a surgically challenging condition. Virtual reality (VR) reconstruction aids surgeons to foresee the anatomy ahead of Nephron Sparing Surgery (NSS). Three-dimensional (3D) visualisation improves the anatomical orientation of surgeons performing NSS. We herewith report a case of BWT where VR planning and 3D printing were used to aid NSS. Conventional imaging is often found to be inadequate while assessing the tumour-organ-vascular anatomy. Advances like VR and 3D printing help surgeons plan better for complex surgeries like bilateral NSS. Next-generation extended reality tools will likely aid robotic-assisted precision NSS and improve patient outcomes.
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Neoplasias Renales , Realidad Virtual , Tumor de Wilms , Niño , Humanos , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/cirugía , Neoplasias Renales/patología , Tumor de Wilms/diagnóstico por imagen , Tumor de Wilms/cirugía , Tumor de Wilms/patología , Nefrectomía/métodos , Nefronas/cirugía , Nefronas/patología , Imagenología Tridimensional/métodosRESUMEN
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.
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Craneofaringioma , Neoplasias Hipofisarias , Terapia de Protones , Humanos , Craneofaringioma/radioterapia , Craneofaringioma/diagnóstico por imagen , Femenino , Masculino , Terapia de Protones/métodos , Adulto , Neoplasias Hipofisarias/radioterapia , Neoplasias Hipofisarias/diagnóstico por imagen , Neoplasias Hipofisarias/cirugía , Adolescente , Niño , Adulto Joven , India , Preescolar , Recurrencia Local de Neoplasia/radioterapia , Radioterapia Guiada por Imagen/métodos , Resultado del Tratamiento , Imagen por Resonancia MagnéticaRESUMEN
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.
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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.
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Astrocitoma , Neoplasias Encefálicas , Humanos , Protones , Marcadores de Spin , Amidas , Astrocitoma/diagnóstico por imagen , Astrocitoma/patología , Imagen por Resonancia Magnética/métodos , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , BiomarcadoresRESUMEN
INTRODUCTION: Radiation-induced oral mucositis (RIOM), is a common, debilitating, acute side effect of radiotherapy for oral cavity (OC) and oropharyngeal (OPx) cancers; technical innovations for reducing it are seldom discussed. Intensity-modulated-proton-therapy (IMPT) has been reported extensively for treating OPx cancers, and less frequently for OC cancers. We aim to quantify the reduction in the likelihood of RIOM in treating these 2 subsites with IMPT compared to Helical Tomotherapy. MATERIAL AND METHODS: We report acute toxicities and early outcomes of 22 consecutive patients with OC and OPx cancers treated with IMPT, and compare the dosimetry and normal tissue complication probability (NTCP) of ≥ grade 3 mucositis for IMPT and HT. RESULTS: Twenty two patients, 77% males, 41% elderly and 73% OC subsite, were reviewed. With comparable target coverage, IMPT significantly reduced the mean dose and D32, D39, D45, and D50, for both the oral mucosa (OM) and spared oral mucosa (sOM). With IMPT, there was a 7% absolute and 16.5% relative reduction in NTCP for grade 3 mucositis for OM, compared to HT. IMPT further reduced NTCP for sOM, and the benefit was maintained in OC, OPx subsites and elderly subgroup. Acute toxicities, grade III dermatitis and mucositis, were noted in 50% and 45.5% patients, respectively, while 22.7% patients had grade 3 dysphagia. Compared with published data, the hospital admission rate, median weight loss, feeding tube insertion, unplanned treatment gaps were lower with IMPT. At a median follow-up of 15 months, 81.8% were alive; 72.7%, alive without disease and 9%, alive with disease. CONCLUSION: The dosimetric benefit of IMPT translates into NTCP reduction for grade 3 mucositis compared to Helical Tomotherapy for OPx and OC cancers and encourages the use of IMPT in their management.
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Neoplasias de la Boca , Mucositis , Neoplasias Orofaríngeas , Terapia de Protones , Traumatismos por Radiación , Radioterapia de Intensidad Modulada , Estomatitis , Masculino , Humanos , Anciano , Femenino , Mucositis/etiología , Terapia de Protones/efectos adversos , Planificación de la Radioterapia Asistida por Computador/efectos adversos , Órganos en Riesgo , Neoplasias Orofaríngeas/radioterapia , Probabilidad , Estomatitis/etiología , Traumatismos por Radiación/prevención & control , Traumatismos por Radiación/complicaciones , Radioterapia de Intensidad Modulada/efectos adversos , Dosificación RadioterapéuticaRESUMEN
Lung cancer (LC) is one of the leading causes of cancer deaths worldwide. In India, the incidence of LC is increasing rapidly, and a majority of the patients are diagnosed at advanced stages of the disease when treatment is less likely to be effective. Recent therapeutic developments have significantly improved survival outcomes in patients with LC. Prompt specialist referral remains critical for early diagnosis for improved patient survival. In the Indian scenario, distinguishing LC from benign and endemic medical conditions such as tuberculosis can pose a challenge. Hence, awareness regarding the red flags-signs and symptoms that warrant further investigations and referral-is vital. This review is an effort toward encouraging general physicians to maintain a high index of clinical suspicion for those at risk of developing LC and assisting them in refering patients with concerning symptoms to specialists or multidisciplinary teams as early as possible.
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Head Neck cancer patients treated with modern proton therapy need special attention during mould room procedures. In addition to usual mould room practices, patients undergoing Intensity Modulated Proton Therapy (IMPT) require attention to the special characteristics of protons viz., sensitivity to beam path and its alteration, sharp dose fall off and end of range. In this article, we discuss the Standard Operating Procedure (SOP) for HNC immobilization and simulation for IMPT, developed and practiced at our centre. The SOP details each step during the immobilization and simulation process, with nuances specific to IMPT.
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Purpose: An indolent nature, with a high risk of local recurrence along with the potential for distant metastases, makes the relatively rare adenoid cystic carcinomas (ACCs) of the head-and-neck region, a unique entity. In the base of skull (BOS) region, these cancers require radiation doses as high as 70-72 GyE in proximity to critical structures. Proton therapy (PT) confers physical and radiobiological advantages and local control at 2-5 years exceeding 80% in most series, compared with below 60% with photon-based techniques. We report a case series of ACCs of the BOS, treated with image-guided, intensity-modulated PT (IMPT). Materials and Methods: During 2019-2020, we treated six patients with skull-base ACC IMPT with on-board, cross-sectional image guidance. Dosimetric data, toxicity, and early outcomes were studied, and a comparative review of literature was done. Results: Three patients underwent PT/proton-photon treatment for residual/inoperable lesions and three patients underwent reirradiation for recurrent lesions. The prescription was 70 GyE in 31-35 fractions, and 95% of the clinical target volume (CTV) received 98% of the prescribed dose in five of the six patients. Grade 3 mucositis and skin reactions were noted in two patients and one patient, respectively. Five of the six patients were controlled locally at a median follow-up of 15 months. Conclusion: The radiobiological and physical characteristics of PT help to deliver high doses with excellent CTV coverage in skull-base ACCs, adjacent to critical neurological structures.
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Carcinoma Adenoide Quístico , Neoplasias de Cabeza y Cuello , Terapia de Protones , Radioterapia de Intensidad Modulada , Carcinoma Adenoide Quístico/patología , Carcinoma Adenoide Quístico/radioterapia , Neoplasias de Cabeza y Cuello/etiología , Humanos , Terapia de Protones/efectos adversos , Dosificación Radioterapéutica , Base del Cráneo/patologíaRESUMEN
Purpose: To compare the late gastrointestinal (GI) and genitourinary toxicities (GU) estimated using multivariable normal tissue complication probability (NTCP) models, between pencil-beam scanning proton beam therapy (PBT) and helical tomotherapy (HT) in patients of high-risk prostate cancers requiring pelvic nodal irradiation (PNI) using moderately hypofractionated regimen. Materials and Methods: Twelve consecutive patients treated with PBT at our center were replanned with HT using the same planning goals. Six late GI and GU toxicity domains (stool frequency, rectal bleeding, fecal incontinence, dysuria, urinary incontinence, and hematuria) were estimated based on the published multivariable NTCP models. The ΔNTCP (difference in absolute NTCP between HT and PBT plans) for each of the toxicity domains was calculated. A one-sample Kolmogorov-Smirnov test was used to analyze distribution of data, and either a paired t test or a Wilcoxon matched-pair signed rank test was used to test statistical significance. Results: Proton beam therapy and HT plans achieved adequate target coverage. Proton beam therapy plans led to significantly better sparing of bladder, rectum, and bowel bag especially in the intermediate range of 15 to 40 Gy, whereas doses to penile bulb and femoral heads were higher with PBT plans. The average ΔNTCP for grade (G)2 rectal bleeding, fecal incontinence, stool frequency, dysuria, urinary incontinence, and G1 hematuria was 12.17%, 1.67%, 2%, 5.83%, 2.42%, and 3.91%, respectively, favoring PBT plans. The average cumulative ΔNTCP for GI and GU toxicities (ΣΔNTCP) was 16.58% and 11.41%, respectively, favoring PBT. Using a model-based selection threshold of any G2 ΔNTCP >10%, 67% (8 patients) would be eligible for PBT. Conclusion: Proton beam therapy plans led to superior sparing of organs at risk compared with HT, which translated to lower NTCP for late moderate GI and GU toxicities in patients of prostate cancer treated with PNI. For two-thirds of our patients, the difference in estimated absolute NTCP values between PBT and HT crossed the accepted threshold for minimal clinically important difference.
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BACKGROUND: To report our experience with image guided pencil beam proton beam therapy (PBT) for craniospinal irradiation (CSI). MATERIALS AND METHODS: Between January 2019 and December 2021, we carried out a detailed audit of the first forty patients treated with PBT. We had recorded acute toxicities, reporting early outcomes and discuss limitations of current contouring guidelines during CSI PBT planning. RESULTS: Median age of the patient cohort was 8 years, and histologies include 20 medulloblastoma, 7 recurrent ependymoma, 3 pineoblastoma, 3 were germ cell tumors and remaining 7 constituted other diagnoses. Forty percent patients received concurrent chemotherapy. Median CSI dose was 23.4 Gy (Gray; range 21.6-35 Gy). Thirty-five patients (87.5%) completed their CSI without interruption, 5 required hospital admission. No patient had grade 2/ > weight loss during the treatment. Forty-five percent (18) developed grade 1 haematological toxicities and 20% (8) developed grade 2 or 3 toxicities; none had grade 4 toxicities. At median follow up of 12 months, 90% patients are alive of whom 88.9% are having local control. Special consideration with modification in standard contouring used at our institute helped in limiting acute toxicities in paediatric CSI patients. CONCLUSION: Our preliminary experience with modern contemporary PBT using pencil beam technology and daily image guidance in a range of tumours suitable for CSI is encouraging. Patients tolerated the treatment well with acceptable acute toxicity and expected short-term survival outcome. In paediatric CSI patients, modification in standard contouring guidelines required to achieve better results with PBT.
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Neoplasias Cerebelosas , Irradiación Craneoespinal , Terapia de Protones , Niño , Irradiación Craneoespinal/métodos , Humanos , Recurrencia Local de Neoplasia/etiología , Terapia de Protones/métodos , ProtonesRESUMEN
Neuropathy of dorsal scapular nerve (DSN) following neck dissections or radiotherapy has not been reported so far nor has its treatment in the form of hydro-dissection. Hydro-dissection of nerve under ultrasound guidance has been receiving more attention in the recent past and it is a minimally invasive procedure. We report here a case of neuropathy of DSN following radiotherapy in a patient for whom we could at least provide pain relief as a palliative measure during his last 6 months of life.
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PURPOSE: Proton beam therapy (PBT) has been a preferred modality in pediatric malignancies requiring radiotherapy. We report our preliminary experience of treating consecutive patients younger than 25 years with image-guided pencil beam scanning PBT from the first and only center on the Indian subcontinent. METHODS: Patients were selected for PBT on the basis of a multidisciplinary tumor board decision. Patient demographic data, as well as tumor and treatment-related characteristics of the cohort, were captured. Patient and treatment-related factors and their association with acute toxicities were analyzed using univariable and multivariable analyses. RESULTS: Forty-seven patients (27 with CNS and 20 with non-CNS tumors) with a median age of 9 years (range, 2-25 years) were evaluated. Most common diagnoses were ependymoma, rhabdomyosarcoma, and glioma. Seventy-seven percent of patients traveled more than 500 km, and 70% of them lived in metropolitan cities. Forty-nine percent of patients had recurrent disease at presentation, and 15% had received a previous course of radiation. The median dose delivered was 54.8 cobalt gray equivalents (range, 40.0-70.4 cobalt gray equivalents) to a median clinical target volume of 175 mL (range, 18.7-3,083.0 mL), with 34% of patients requiring concurrent chemotherapy (CCT). Acute grade 2 and grade 3 dermatitis, mucositis, and hematologic toxicity was noted in 45% and 2%, 34% and 0%, and 38% and 30% of patients, respectively. Grade 2 fatigue was noted in 26% of patients. On multivariable analysis, for CNS tumors, both CCT and craniospinal irradiation were independently associated with ≥ 2 grade hematologic toxicity, whereas among non-CNS tumors, a clinical target volume > 150 mL was associated with ≥ 2 grade fatigue, head and neck irradiation was associated with ≥ 2 grade mucositis, and CCT was associated with grade ≥ 2 hematologic toxicity. CONCLUSION: This study demonstrates safe implementation of a PBT program for children and young adults on the Indian subcontinent. Image-guided pencil beam scanning PBT in judiciously selected patients is feasible and can be delivered with acceptable acute toxicities.
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Irradiación Craneoespinal , Ependimoma , Terapia de Protones , Rabdomiosarcoma , Adolescente , Adulto , Niño , Preescolar , Humanos , India , Terapia de Protones/efectos adversos , Adulto JovenRESUMEN
There is no ideal detector-phantom combination to perform patient specific quality assurance (PSQA) for Total Marrow (TMI) and Lymphoid (TMLI) Irradiation plan. In this study, 3D dose reconstruction using mega voltage computed tomography detectors measured Leaf Open Time Sinogram (LOTS) was investigated for PSQA of TMI/TMLI patients in helical tomotherapy. The feasibility of this method was first validated for ten non-TMI/TMLI patients, by comparing reconstructed dose with (a) ion-chamber (IC) and helical detector array (ArcCheck) measurement and (b) planned dose distribution using 3Dγ analysis for 3%@3mm and dose to 98% (D98%) and 2% (D2%) of PTVs. Same comparison was extended for ten treatment plans from five TMI/TMLI patients. In all non-TMI/TMLI patients, reconstructed absolute dose was within ± 1.80% of planned and IC measurement. The planned dose distribution agreed with reconstructed and ArcCheck measured dose with mean (SD) 3Dγ of 98.70% (1.57%) and 2Dγ of 99.48% (0.81%). The deviation in D98% and D2% were within 1.71% and 4.10% respectively. In all 25 measurement locations from TMI/TMLI patients, planned and IC measured absolute dose agreed within ± 1.20%. Although sectorial fluence verification using ArcCHECK measurement for PTVs chest from the five upper body TMI/TMLI plans showed mean ± SD 2Dγ of 97.82% ± 1.27%, the reconstruction method resulted poor mean (SD) 3Dγ of 92.00% (± 5.83%), 64.80% (± 28.28%), 69.20% (± 30.46%), 60.80% (± 19.37%) and 73.2% (± 20.36%) for PTVs brain, chest, torso, limb and upper body respectively. The corresponding deviation in median D98% and D2% of all PTVs were < 3.80% and 9.50%. Re-optimization of all upper body TMI/TMLI plans with new pitch and modulation factor of 0.3 and 3 leads significant improvement with 3Dγ of 100% for all PTVs and median D98% and D2% < 1.6%. LOTS based PSQA for TMI/TMLI is accurate, robust and efficient. A field width, pitch and modulation factor of 5 cm, 0.3 and 3 for upper body TMI/TMLI plan is suggested for better dosimetric outcome and PSQA results.
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Médula Ósea/efectos de la radiación , Radiometría/métodos , Planificación de la Radioterapia Asistida por Computador/métodos , Irradiación Corporal Total/métodos , Tomografía Computarizada de Haz Cónico , Humanos , Modelación Específica para el Paciente , Fantasmas de Imagen , Dosificación Radioterapéutica , Radioterapia de Intensidad Modulada , Reproducibilidad de los ResultadosRESUMEN
PURPOSE: To standardize the technique; evaluate resources requirements and analyze our early experience of total marrow and lymphoid irradiation (TMLI) as part of the conditioning regimen before allogenic bone marrow transplantation using helical tomotherapy. MATERIALS AND METHODS: Computed tomography (CT) scanning and treatment were performed in head first supine (HFS) and feet first supine (FFS) orientations with an overlap at mid-thigh. Patients along with the immobilization device were manually rotated by 180° to change the orientation after the delivery of HFS plan. The dose at the junction was contributed by a complementary dose gradient from each of the plans. Plan was to deliver 95% of 12 Gy to 98% of clinical target volume with dose heterogeneity <10% and pre-specified organs-at-risk dose constraints. Megavoltage-CT was used for position verification before each fraction. Patient specific quality assurance and in vivo film dosimetry to verify junction dose were performed in all patients. RESULTS: Treatment was delivered in two daily fractions of 2 Gy each for 3 days with at least 8-hour gap between each fraction. The target coverage goals were met in all the patients. The average person-hours per patient were 16.5, 21.5, and 25.75 for radiation oncologist, radiation therapist, and medical physicist, respectively. Average in-room time per patient was 9.25 hours with an average beam-on time of 3.32 hours for all the 6 fractions. CONCLUSION: This report comprehensively describes technique and resource requirements for TMLI and would serve as a practical guide for departments keen to start this service. Despite being time and labor intensive, it can be implemented safely and robustly.