Learning from Limited and Incomplete Data: A Multimodal Framework for Predicting Pathological Response in NSCLC

Major pathological response (pR) following neoadjuvant therapy is a clinically meaningful endpoint in non-small cell lung cancer, strongly associated with improved survival. However, accurate preoperative prediction of pR remains challenging, particularly in real-world clinical settings characterized by limited data availability and incomplete clinical profiles. In this study, we propose a multimodal deep learning framework designed to address these constraints by integrating foundation model-based CT feature extraction with a missing-aware architecture for clinical variables. This approach enables robust learning from small cohorts while explicitly modeling missing clinical information, without relying on conventional imputation strategies. A weighted fusion mechanism is employed to leverage the complementary contributions of imaging and clinical modalities, yielding a multimodal model that consistently outperforms both unimodal imaging and clinical baselines. These findings underscore the added value of integrating heterogeneous data sources and highlight the potential of multimodal, missing-aware systems to support pR prediction under realistic clinical conditions.

Retrieval-Augmented Anatomical Guidance for Text-to-CT Generation

Text-conditioned generative models for volumetric medical imaging provide semantic control but lack explicit anatomical guidance, often resulting in outputs that are spatially ambiguous or anatomically inconsistent. In contrast, structure-driven methods ensure strong anatomical consistency but typically assume access to ground-truth annotations, which are unavailable when the target image is to be synthesized. We propose a retrieval-augmented approach for Text-to-CT generation that integrates semantic and anatomical information under a realistic inference setting. Given a radiology report, our method retrieves a semantically related clinical case using a 3D vision-language encoder and leverages its associated anatomical annotation as a structural proxy. This proxy is injected into a text-conditioned latent diffusion model via a ControlNet branch, providing coarse anatomical guidance while maintaining semantic flexibility. Experiments on the CT-RATE dataset show that retrieval-augmented generation improves image fidelity and clinical consistency compared to text-only baselines, while additionally enabling explicit spatial controllability, a capability inherently absent in such approaches. Further analysis highlights the importance of retrieval quality, with semantically aligned proxies yielding consistent gains across all evaluation axes. This work introduces a principled and scalable mechanism to bridge semantic conditioning and anatomical plausibility in volumetric medical image synthesis. Code will be released.

Handling Missing Modalities in Multimodal Survival Prediction for Non-Small Cell Lung Cancer

Accurate survival prediction in Non-Small Cell Lung Cancer (NSCLC) requires the integration of heterogeneous clinical, radiological, and histopathological information. While Multimodal Deep Learning (MDL) offers a promises for precision prognosis and survival prediction, its clinical applicability is severely limited by small cohort sizes and the presence of missing modalities, often forcing complete-case filtering or aggressive imputation. In this work, we present a missing-aware multimodal survival framework that integrates Computed Tomography (CT), Whole-Slide Histopathology (WSI) Images, and structured clinical variables for overall survival modeling in unresectable stage II-III NSCLC. By leveraging Foundation Models (FM) for modality-specific feature extraction and a missing-aware encoding strategy, the proposed approach enables intermediate multimodal fusion under naturally incomplete modality profiles. The proposed architecture is resilient to missing modalities by design, allowing the model to utilize all available data without being forced to drop patients during training or inference. Experimental results demonstrate that intermediate fusion consistently outperforms unimodal baselines as well as early and late fusion strategies, with the strongest performance achieved by the fusion of WSI and clinical modalities (73.30 C-index). Further analyses of modality importance reveal an adaptive behavior in which less informative modalities, i.e., CT modality, are automatically down-weighted and contribute less to the final survival prediction.

Leveraging MIMIC Datasets for Better Digital Health: A Review on Open Problems, Progress Highlights, and Future Promises

The Medical Information Mart for Intensive Care (MIMIC) datasets have become the Kernel of Digital Health Research by providing freely accessible, deidentified records from tens of thousands of critical care admissions, enabling a broad spectrum of applications in clinical decision support, outcome prediction, and healthcare analytics. Although numerous studies and surveys have explored the predictive power and clinical utility of MIMIC based models, critical challenges in data integration, representation, and interoperability remain underexplored. This paper presents a comprehensive survey that focuses uniquely on open problems. We identify persistent issues such as data granularity, cardinality limitations, heterogeneous coding schemes, and ethical constraints that hinder the generalizability and real-time implementation of machine learning models. We highlight key progress in dimensionality reduction, temporal modelling, causal inference, and privacy preserving analytics, while also outlining promising directions including hybrid modelling, federated learning, and standardized preprocessing pipelines. By critically examining these structural limitations and their implications, this survey offers actionable insights to guide the next generation of MIMIC powered digital health innovations.

MARIA: a Multimodal Transformer Model for Incomplete Healthcare Data

In healthcare, the integration of multimodal data is pivotal for developing comprehensive diagnostic and predictive models. However, managing missing data remains a significant challenge in real-world applications. We introduce MARIA (Multimodal Attention Resilient to Incomplete datA), a novel transformer-based deep learning model designed to address these challenges through an intermediate fusion strategy. Unlike conventional approaches that depend on imputation, MARIA utilizes a masked self-attention mechanism, which processes only the available data without generating synthetic values. This approach enables it to effectively handle incomplete datasets, enhancing robustness and minimizing biases introduced by imputation methods. We evaluated MARIA against 10 state-of-the-art machine learning and deep learning models across 8 diagnostic and prognostic tasks. The results demonstrate that MARIA outperforms existing methods in terms of performance and resilience to varying levels of data incompleteness, underscoring its potential for critical healthcare applications.

A Systematic Review of Intermediate Fusion in Multimodal Deep Learning for Biomedical Applications

Deep learning has revolutionized biomedical research by providing sophisticated methods to handle complex, high-dimensional data. Multimodal deep learning (MDL) further enhances this capability by integrating diverse data types such as imaging, textual data, and genetic information, leading to more robust and accurate predictive models. In MDL, differently from early and late fusion methods, intermediate fusion stands out for its ability to effectively combine modality-specific features during the learning process. This systematic review aims to comprehensively analyze and formalize current intermediate fusion methods in biomedical applications. We investigate the techniques employed, the challenges faced, and potential future directions for advancing intermediate fusion methods. Additionally, we introduce a structured notation to enhance the understanding and application of these methods beyond the biomedical domain. Our findings are intended to support researchers, healthcare professionals, and the broader deep learning community in developing more sophisticated and insightful multimodal models. Through this review, we aim to provide a foundational framework for future research and practical applications in the dynamic field of MDL.

Not Another Imputation Method: A Transformer-based Model for Missing Values in Tabular Datasets

Handling missing values in tabular datasets presents a significant challenge in training and testing artificial intelligence models, an issue usually addressed using imputation techniques. Here we introduce "Not Another Imputation Method" (NAIM), a novel transformer-based model specifically designed to address this issue without the need for traditional imputation techniques. NAIM employs feature-specific embeddings and a masked self-attention mechanism that effectively learns from available data, thus avoiding the necessity to impute missing values. Additionally, a novel regularization technique is introduced to enhance the model's generalization capability from incomplete data. We extensively evaluated NAIM on 5 publicly available tabular datasets, demonstrating its superior performance over 6 state-of-the-art machine learning models and 4 deep learning models, each paired with 3 different imputation techniques when necessary. The results highlight the efficacy of NAIM in improving predictive performance and resilience in the presence of missing data. To facilitate further research and practical application in handling missing data without traditional imputation methods, we made the code for NAIM available at https://github.com/cosbidev/NAIM.

A Deep Learning Approach for Overall Survival Prediction in Lung Cancer with Missing Values

One of the most challenging fields where Artificial Intelligence (AI) can be applied is lung cancer research, specifically non-small cell lung cancer (NSCLC). In particular, overall survival (OS), the time between diagnosis and death, is a vital indicator of patient status, enabling tailored treatment and improved OS rates. In this analysis, there are two challenges to take into account. First, few studies effectively exploit the information available from each patient, leveraging both uncensored (i.e., dead) and censored (i.e., survivors) patients, considering also the events' time. Second, the handling of incomplete data is a common issue in the medical field. This problem is typically tackled through the use of imputation methods. Our objective is to present an AI model able to overcome these limits, effectively learning from both censored and uncensored patients and their available features, for the prediction of OS for NSCLC patients. We present a novel approach to survival analysis with missing values in the context of NSCLC, which exploits the strengths of the transformer architecture to account only for available features without requiring any imputation strategy. By making use of ad-hoc losses for OS, it is able to account for both censored and uncensored patients, as well as changes in risks over time. We compared our method with state-of-the-art models for survival analysis coupled with different imputation strategies. We evaluated the results obtained over a period of 6 years using different time granularities obtaining a Ct-index, a time-dependent variant of the C-index, of 71.97, 77.58 and 80.72 for time units of 1 month, 1 year and 2 years, respectively, outperforming all state-of-the-art methods regardless of the imputation method used.