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Locoregionally advanced paranasal sinus carcinoma. Favorable survival with multimodality therapy.

To determine the efficacy of multimodality treatment for stage III and IV, advanced paranasal carcinoma, we have retrospectively reviewed local control rate and disease-free survival in patients treated at the University of Chicago (Ill). Twelve consecutive patients with stage III or IV, newly diagnosed paranasal sinus carcinoma treated between 1984 and 1991 were included in this study. Multimodality therapy was composed of a sequence of fluorouracil-cisplatin-based neoadjuvant chemotherapy (in 12 of 12 patients) followed by standard surgical resection (11 of 12 patients) and radiotherapy (12 of 12 patients, 45 to 73 Gy) with or without concomitant chemotherapy. Eleven patients (92%) are currently alive and free of disease, with a median follow-up of 55 months (range, 13 to 105 months). One patient died of persistent disease. Failure was attributed to incomplete surgical resection. There was only one major irreversible treatment complication (cisplatin ototoxic reaction). Our preliminary data suggest improved local control and survival with multimodality therapy that includes systemic neoadjuvant chemotherapy and standard tumor resection in patients with advanced paranasal sinus carcinoma. These results are superior to the reported 40% survival with bimodal therapy and are better than those achieved in our institution for other head and neck primaries with the same treatment regimens.

Adult

Multimodal immunotherapy of primary gastrointestinal tumors in rats. 1. Histologic correlation.

The effect of multimodal immunotherapy was studied in rats bearing primary gastrointestinal tumors induced by 1,2-dimethylhydrazine dihydrochloride. Multimodal immune manipulation consisted of combinations of splenectomy, C. parvum, unblocking serum, unblocked lymphoid cells, and levamisole. Such immunologic intervention resulted in significant inhibition of tumor growth, and their metastasis. Ten of 10 untreated rats, 8 of 8 rats treated with splenectomy alone and 10 of 10 rats treated with normal rabbit serum died of progressive tumor growth. None of the rats treated with combinations of splenectomy, unblocking serum, unblocked lymphoid cells, C. parvum and levamisole succumbed to progressive tumor growth during the observation period. The histologic evidence of tumor destruction was obtained in 18 of 22 tumors in rats of groups receiving multimodal immunotherapy.

Animals

Treatment of advanced head and neck cancer: multiple daily dose fractionated radiation therapy and sequential multimodal treatment approach.

Fifty-eight patients with advanced head and neck cancer were entered into a randomised trial comparing chemotherapy (DDP + bleomycin) alone, multiple daily fractionated radiation therapy, and multimodality therapy consisting of chemotherapy plus multiple fractionated radiation therapy. Multimodal therapy gave a significantly higher response rate (69%) than either single-treatment modality. The use of a multiple daily dose fractionation allowed radiation therapy to be completed over 10 treatment days, and the addition of chemotherapy to the radiation treatment did not significantly increase toxicity. Patients receiving multimodal therapy also survived significantly longer (median 50 weeks) than those receiving single-modality therapy (median 24 weeks).

Antineoplastic Combined Chemotherapy Protocols

Multimodal features and prognostic risk assessment in locally advanced gastric cancer patients following neoadjuvant therapy based on machine learning algorithms: a multicenter study.

BACKGROUND: Neoadjuvant therapy (NAT) is recommended for locally advanced gastric cancer (LAGC), but some patients respond poorly. We aimed to construct a multimodal model integrating CT images, transcriptomic sequencing, and clinicopathological data to assess prognosis in LAGC patients receiving NAT. MATERIALS AND METHODS: This multicenter study included 505 LAGC patients who underwent NAT. Radiomic features were extracted from preoperative CT images of 505 patients. RNA-seq was performed on 277 post-NAT specimens, with additional data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases (n&#x2009;=&#x2009;804). Patients were divided into training (168 cases), internal validation (72 cases), and external validation cohorts. Machine learning algorithms identified key radiomic, molecular, and clinical features associated with NAT response, which were then integrated into a multimodal model to predict overall survival (OS) and disease-free survival (DFS). RESULTS: Six radiomic and three molecular features significantly associated with NAT response were selected. Radiomic risk (hazard ratio [HR]: 4.0, P&#x2009;<&#x2009;0.001) and molecular risk (HR: 7.1, P&#x2009;<&#x2009;0.001) were independent prognostic factors. By integrating radiomic risk, molecular risk, and clinical characteristics, a multimodal model (MuMo) was constructed.The C-index results (OS, C-index&#x2009;=&#x2009;0.855; DFS, C-index&#x2009;=&#x2009;0.786) demonstrated that MuMo outperformed the single-modality models and ypTNM staging.Mechanistic analysis suggested that the efficacy of neoadjuvant therapy was significantly enriched in immune-inflammatory pathways. CONCLUSIONS: MuMo can effectively predict postoperative survival risk in LAGC patients receiving NAT, serving as a powerful tool for optimizing prognostic assessment.

Humans

Improving treatment planning accuracy through multimodality imaging.

PURPOSE: In clinical practice, physicians are constantly comparing multiple images taken at various times during the patient's treatment course. One goal of such a comparison is to accurately define the gross tumor volume (GTV). The introduction of three-dimensional treatment planning has greatly enhanced the ability to define the GTV, but there are times when the GTV is not visible on the treatment-planning computed tomography (CT) scan. We have modified our treatment-planning software to allow for interactive display of multiple, registered images that enhance the physician's ability to accurately determine the GTV. METHODS AND MATERIALS: Images are registered using interactive tools developed at the University of North Carolina at Chapel Hill (UNC). Automated methods are also available. Images registered with the treatment-planning CT scan are digitized from film. After a physician has approved the registration, the registered images are made available to the treatment-planning software. Structures and volumes of interest are contoured on all images. In the beam's eye view, wire loop representations of these structures can be visualized from all image types simultaneously. Each registered image can be seamlessly viewed during the treatment-planning process, and all contours from all image types can be seen on any registered image. A beam may, therefore, be designed based on any contour. RESULTS: Nineteen patients have been planned and treated using multimodality imaging from November 1993 through August 1994. All registered images were digitized from film, and many were from outside institutions. Brain has been the most common site (12), but the techniques of registration and image display have also been used for the thorax (4), abdomen (2), and extremity (1). The registered image has been an magnetic resonance (MR) scan in 15 cases and a diagnostic CT scan in 5 cases. In one case, sequential MRs, one before treatment and another after 30 Gy, were used to plan patient's initial fields and boost, respectively. Case illustrations are shown. CONCLUSIONS: We have successfully integrated multimodality imaging into our treatment-planning system, and its routine use is increasing. Multimodality imaging holds out the promise of improving treatment planning accuracy and, thus, takes maximum advantage of three dimensional treatment planning systems.

Humans

Locally advanced breast cancer: early results of a randomised trial of multimodal therapy versus initial hormone therapy.

The aim of this study was to investigate initial treatment of locally advanced breast cancer. Patients were randomised to "multimodal" therapy (pre-operative chemotherapy, Patey mastectomy, flap irradiation and adjuvant hormone therapy) (n = 55), or initial "hormone" therapy (n = 53) with further therapy upon tumour progression. The objective response to chemotherapy was 57% (31/54) after four cycles. Of patients on hormone therapy, 36% (19/53) had an objective response and 32% (17/53) disease stasis at a 6 month assessment. At a median 30 months follow-up, there was no notable difference in development of metastases or survival: only 6 patients have uncontrolled loco-regional relapse (4 "hormonal", 2 "multimodal"). The number of treatments per patient required for this loco-regional control was lower in the "hormone" group (mean 2.13 versus 4.20 in the "multimodal" group). This small study has shown that the use of consecutive therapies, with the aim of tumour control, does not appear to compromise outcome in comparison with initial "multi-modal" therapy. Adopting such a policy may allow some patients to avoid unnecessary treatments.

Adult

Stroop interference based on the multimodal correlates of haptic size and auditory pitch.

In a preliminary experiment subjects were asked to explore three wooden knobs of different sizes and to rate each one on a series of 7-point scales. The results confirmed that an object may possess a number of multimodal qualities that are contingent on its haptic size. The pattern of intercorrelations between the qualities was consistent with the pattern that is observed when subjects respond to pure auditory tones varying in pitch. For example, small (high-pitched) sounds, like small objects, are judged to be sharp, thin, light, weak, fast, tense, and bright. The main experiments used a paradigm based on the Stroop interference effect. Subjects were required to press one of two keys as quickly as possible depending on which of four possible words appeared in the centre of the screen. A 50 Hz or a 5500 Hz tone accompanied each test word, and subjects responded on two keys that differed in size. Subjects were found to respond more slowly when either the pitch of the incidental sound or the size of the key on which they responded was incongruent with the multimodal features represented by the test word. The results confirm that people are automatically and immediately sensitive to the multimodal features of a stimulus when direct sensory evidence for the features is absent.

Form Perception

mmContext: an open framework for multimodal contrastive learning of omics and text data.

SUMMARY: Multimodal approaches are increasingly leveraged for integrating omics data with textual biological knowledge. Yet there is still no accessible, standardized framework that enables systematic comparison of omics representations with different text encoders within a unified workflow. We present mmContext, a lightweight and extensible multimodal embedding framework built on top of the open-source Sentence Transformers library. The software allows researchers to train or apply models that jointly embed omics and text data using any numeric representation stored in an AnnData.obsm layer and any text encoder available in Hugging Face. mmContext supports integration of diverse biological text sources and provides pipelines for training, evaluation, and data preparation. We train and evaluate models for a RNA-Seq and text integration task, and demonstrate their utility through zero-shot classification of cell types and diseases across four independent datasets. By releasing all models, datasets, and tutorials openly, mmContext enables reproducible and accessible multimodal learning for omics-text integration. AVAILABILITY AND IMPLEMENTATION: Pretrained checkpoints and full source code for our custom MMContextEncoder are available on Hugging Face huggingface.co/jo-mengr. The Python package github.com/mengerj/mmcontext provides the model implementation and training and evaluation scripts for custom training. The releases for the publication can be accessed via zenodo: adata_hf_datasets: doi.org/10.5281/zenodo.19185217 and mmContext: doi.org/10.5281/zenodo.19185493.

Computational Biology

Aims and methodological problems in multimodal treatment studies.

The paper outlines the growing acceptance and use of multimodal treatment approaches to treat a variety of psychiatric disorders in childhood and adolescence. It then explores some of the problems of multimodal treatment studies. Problems in assessing outcome of efficacy of the interventions, particularly as they pertain to specific interventions and particular areas of functioning are discussed as well as the issues of appropriate control and comparison groups. The problems with regard to appropriate control and comparison groups are explored with respect to diagnosis and interventions. Finally, an ongoing multimodal treatment study of children with attention deficit hyperactive disorder is used to illustrate how some of the problems described can be solved.

Adolescent

Ten-year outcome of patients with advanced epithelial ovarian carcinoma treated with cisplatin-based multimodality therapy.

PURPOSE: At the end of the 1970s it was thought that advanced epithelial ovarian cancer (EOC) could be cured by multimodality treatment using surgery, cisplatin-based combination chemotherapy, and radiotherapy (RT). Such multimodality treatment was used as standard therapy at our institution. Our long-term results are reviewed. PATIENTS AND METHODS: One hundred ninety-five previously untreated patients with stage III or IV EOC were treated between April 1979 and December 1982. All patients were to have debulking surgery, when feasible, followed by the administration of doxorubicin and cisplatin at 50 mg/m2 every 3 weeks until a total dose of doxorubicin of 450 mg/m2 had been reached. RT was used in addition in patients with disease remaining after the chemotherapy. Maintenance chemotherapy with oral cyclophosphamide and hexamethylmelamine (altretamine) was administered to patients who did not have a documented histologic complete remission. RESULTS: The 10-year overall and failure-free survivals were 4% and 8%, respectively. The median overall survival was 2 years. The achievement of a histologic complete response (n = 32) did not equate to cure because 20 (63%) of the patients eventually relapsed. Multivariate analysis identified residual disease of greater or less than 2 cm as the only independent prognostic factor. CONCLUSIONS: Our multimodality treatment program was noncurative for the majority of the patients. Innovative therapies are needed before we can hope to cure such disease.

Adult

Stage III neuroblastoma over 1 year of age at diagnosis: improved survival with intensive multimodality therapy including multiple alkylating agents.

PURPOSE: A nonrandomized, single-arm trial was conducted to assess the efficacy of multimodality therapy including intensive chemotherapy with multiple alkylating agents in the treatment of children with Evans stage III neuroblastoma older than 1 year at diagnosis. PATIENTS AND METHODS: Twenty-five patients with a median age of 18 months at diagnosis were treated with multimodality therapy including surgery and chemotherapy using either nitrogen mustard (mechlorethamine), doxorubicin, cisplatin, dacarbazine (DTIC), vincristine, and cyclophosphamide (MADDOC) or cisplatin and cyclophosphamide induction followed by maintenance MADDOC (induction MADDOC) protocols. Sixteen of 25 patients also received radiotherapy to the tumor bed and primary lymph nodes. Event-free survival (EFS) was compared with that reported previously in the literature. N-myc amplification was evaluated prospectively and the Shimada classification was evaluated retrospectively as potential prognostic factors. RESULTS: We report a 72% EFS (95% confidence interval +/- 18%) with a median follow-up of 85 months. EFS was significantly worse for patients with tumors demonstrating N-myc amplification (P = .018). Patients classified as favorable according to the Shimada system experienced a significantly better EFS (P = .04), but unfavorable patients still maintained a 60% EFS. CONCLUSION: Intensive multimodality treatment including MADDOC and induction MADDOC chemotherapy provides a very good EFS for children older than 1 year who have stage III neuroblastoma. Children classified as favorable according to the Shimada system have a better prognosis. Patients whose tumors demonstrate N-myc amplification have a poor prognosis despite therapy.

Alkylating Agents

Multimodal radiography: a new imaging technique and system for oral diagnosis.

The multimodal radiography system is based on the combined use of narrow-beam radiography and spiral tomography in one set of equipment. The essentials of a system are a multifunction unit, preprogrammed imaging procedures for various dentomaxillofacial objects and a co-ordinate system for object location. Four years of clinical experience have shown that multimodal radiography is effective for depicting dentomaxillofacial structures for diagnostic purposes. The detailed narrow beam imaging mode of multimodal radiography has also been compared with intraoral radiography as regards their abilities to reveal periodontal and periapical lesions. Preliminary results indicate that detailed narrow beam radiography is more accurate than intraoral radiography in the diagnosis of periodontal and periapical pathology.

Equipment Design

[Radical surgical intervention with conventional radiation versus multimodality therapy protocol in undifferentiated thyroid cancer].

Out of a total of 550 patients with thyroid cancer diagnosed over the 16-year period 1972-June 1989, 44 showed undifferentiated carcinoma and were treated by thyreoidectomy and early postoperative external irradiation. In order to analyse the outcome in patients treated by primary surgery in contrast to patients treated by means of a multimodal therapy concept we compared our surgical procedures with regard to primary surgical approach, early postoperative course, operative complications and survival to the data on the multimodal therapy concept of the Karolinska Hospital reported by E. Tallroth et al. 1987. A significantly better survival was correlated with radical (n = 20) versus palliative tumour resection (n = 24) (p less than 0.001), and total thyroidectomy (n = 25) versus subtotal thyroidectomy (n = 19) (p less than 0.006). Radical surgery with early postoperative external irradiation revealed no postoperative mortality and no symptomatic cervical tumour recurrence. By contrast, palliative surgery, particularly in the case of synchronous tracheotomy, was attended by a relatively high mortality (29%) and symptomatic local recurrences. The results of this study suggest that in undifferentiated thyroid carcinoma an attempt at radical tumour resection should be undertaken, since multimodal therapy procedures revealed a significantly highly complication rate (up to 36%) and, in comparison with a radical surgical treatment policy, showed a higher rate of local recurrences (0% vs. 48%) and a lower survival (mean survival 42 vs. 15 months).

Aged

[Radiotherapy in the multimodality treatment of retinoblastomas in children].

The results of multimodality therapy of 50 children with uni- or bilateral retinoblastoma were assessed. Gamma-beam therapy with the application of a special protective collimator and polychemotherapy were used as modalities supplementing eye extirpation. Some patients were irradiated prior to operation, the others following it. Despite a slight decrease in a tumor radiation dose in the first group, 2-year survival rates in both groups were the same. Of 32 patients 30 (94%) in both groups have been alive for 2 yrs. without signs of disease after multimodality therapy. Patients with Stage I retinoblastoma were subjected to chemo- and radiotherapy; 16 out of 18 patients have been alive for 2 yrs. It has been stressed that radiation therapy is an important component in multimodality therapy. It can be used as a modality of the combined method of tumor surgical removal or as a method of radical therapy in early forms of the disease.

Antineoplastic Combined Chemotherapy Protocols

[Tumors of the biliary tract: possibilities of multimodality therapy].

BACKGROUND: Tumours of the biliary system (NBS) account for as many as 16% of all tumours of the GIT. Early diagnosis is difficult, contemporary treatment is not satisfactory and the prognosis is poor. It seems that one of the few therapeutic perspectives is multimodal treatment. The objective of the present work is to assemble experience with multimodal treatment of NBS. METHODS AND RESULTS: From January 1987 to December 1993 347 patients with NBS were treated, using bilioduodenal endoprostheses (BDE). In 26 patients treatment was supplemented by regional chemotherapy, in 10 by intraluminal radiotherapy, using lr 192. Average periods of survival:BDE 230 days, BDE+regional chemotherapy 662 days. Endoprostheses+intraluminal radiotherapy-survival period 96-293 days. The investigation has not yet been completed, as the majority of patients still survives. CONCLUSIONS: Implantation of BDE combined with regional chemotherapy significantly prolongs the life of patients with NBS. It seems that similar results will be obtained also by a combination of BDE and intraluminal radiotherapy. Multimodal treatment of NBS can be nowadays considered the method of choice in the treatment of tumours in this region.

Adult

[Preoperative hypoxia-radiotherapy in multimodal treatment of patients with stage III colonic cancer].

The paper analyzes the results of surgical and multimodality therapies for 237 patients with Stage III colonic cancer, which were divided into 3 groups. Group 1 included 119 patients undergone only surgical management, Group 2 comprised 43 who were additionally treated with intensive radiation (4 Gy daily for 5 days) and Group 3 consisted of 75 patients who were irradiated in the presence of overall hypoxia evoked by breathing a gaseous mixture containing 9% oxygen. A five-year follow-up has indicated that there are significantly higher survival rates among those who have received a multimodality therapy rather than those merely operated on (82 +/- 5 and 53 +/- 9%, respectively). A short-term gaseous hypoxia has been found to reduce the incidence of systemic radiation reactions in patients during preoperative radiation and to fail to lower the efficiency of multimodality therapy.

Colonic Neoplasms

Multimodal intervention benefits: Responder analysis of J-MINT PRIME Kanagawa trial.

INTRODUCTION: The J-MINT PRIME Kanagawa trial was an 18-month multimodal intervention (incorporating exercise, nutrition, and metabolic management) for dementia prevention. Because the primary analysis showed no significant benefits, we performed an exploratory responder analysis to identify responsive subpopulations. METHODS: We analyzed the Full Analysis Set comprising 188 participants. Classification and regression tree (CART) analysis, applied to the intervention arm, identified baseline predictors of cognitive improvement. These rules were then applied to the entire cohort to evaluate treatment effects on the Mini-Mental State Examination (MMSE) using fully adjusted mixed-effects models for repeated measures (MMRM). RESULTS: CART identified a "Target Group" (N = 108) characterized by baseline profiles such as an MMSE score < 28 or specific metabolic ranges (e.g., LDL-C < 135 mg/dL). Within this target group, the intervention significantly preserved MMSE trajectories compared with the control group (group &#xd7; time interaction, P = 0.022). In contrast, the Non-Target Group (N = 80), consisting of high-functioning individuals (MMSE &#x2265; 28), exhibited no significant group &#xd7; time interaction. DISCUSSION: Multimodal interventions may effectively preserve global cognition in older adults with sub-threshold cognitive decline. Careful targeting of appropriate populations, while considering potential longitudinal measurement artifacts (e.g., practice effects), is essential. These findings provide a hypothesis-generating framework that warrants external validation in future prevention trials.

Humans

Diagnosing the undiagnosed: AI-enhanced multimodal modeling for placental mesenchymal dysplasia in high-risk pregnancies.

Placental mesenchymal dysplasia (PMD) is a rare vascular placental disorder that mimics molar pregnancy but often coexists with a viable fetus, making its misdiagnosis potentially devastating. In high-risk pregnancies, artificial intelligence (AI)-enhanced multimodal modeling - incorporating imaging, genomics, proteomics, and clinical features - offers a transformative diagnostic strategy. Leveraging Bayesian hyperparameter optimization for model refinement, this approach improves diagnostic accuracy while reducing uncertainty and clinician hesitation. Recent clinical studies support its efficacy and interpretability through SHAP and LIME models, while real-time surgical enhancements using Bayesian methods highlight its broader clinical utility. Despite current challenges such as data heterogeneity and integration barriers, multimodal AI provides unprecedented resolution in placental analysis, enabling precise differentiation between PMD and similar fetopathies. Ultimately, this advancement supports timely, non-invasive diagnosis, personalized management, and emotionally informed decision-making aligned with ethical AI implementation standards.

Bayesian optimization