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PubMed1993

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↗

PubMed1978

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↗

PubMed1984

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↗

PubMed2001

Comparison of intraoperative radiation therapy-containing multimodality treatment with historical treatment modalities for locally recurrent rectal cancer.

PURPOSE: Treatment protocols for patients with locally recurrent rectal cancer have changed in the last two decades. Subsequently, treatment goals shifted from palliation to possible cure. In this retrospective study, we explored the treatment variables that may have contributed to the improvement in outcome by comparing three treatment modalities from two collaborating institutions in patients with similar tumor characteristics. METHODS: Ninety-four patients were treated with electron-beam radiation therapy only (1975-1990), 19 with combined preoperative electron-beam radiation therapy and surgery (1989-1996), and 33 with intraoperative radiation therapy-multimodality treatment (1994-1999). Intraoperative radiation therapy was delivered either as intraoperative electron-beam radiotherapy (10-17.5 Gy) in 20 patients or as intraoperative high-dose-rate brachytherapy (10 Gy) in 13 patients. No patient had received prior electron-beam radiation therapy. RESULTS: The three-year survival, disease-free survival, and local control rates were 14, 8, and 10 percent, respectively, in the electron-beam radiation therapy-only group and 11, 0, and 14 percent, respectively, in the combined electron-beam radiation therapy-surgery group. The overall intraoperative radiation therapy-multimodality treatment group showed significantly better three-year survival, disease-free survival, and local control rates of 60, 43, and 73 percent, respectively, compared with the historical control groups (P < 0.001). CONCLUSION: The outcome of patients with locally recurrent rectal cancer was improved after the introduction of intraoperative radiation therapy-multimodality treatment.

Aged↗

PubMed1998

[Combination therapy in oncology (multimodal treatment) in pancreatic tumors].

The majority of patients with pancreatic cancer have systemic disease already at diagnosis, and nearly all patients will develop recurrence following radical resection. Thus, surgical treatment alone is insufficient. The paper focuses on adjuvant multimodal treatment and reviews the current status of pre- and postoperative chemoradiation, intraoperative radiotherapy (IORT), adjuvant chemotherapy, and regional infusion therapy. Studies in this area are hampered by often being non-randomized and with too few patients included. Overall there presently is no adjuvant multimodal treatment which can be suggested for routine use. However, two ongoing prospective randomized studies (ESPAC-1 and an EORTC study) will have enough statistical power to give reliable information on the topic. It is hoped that these and other studies will form the basis for further proper clinical trials on multimodal treatment in pancreatic cancer with the aim at long last to improve the extremely poor survival in these patients.

Adenocarcinoma↗

PubMed2001

Squamous cell carcinoma of the esophagus: multimodal therapy in locally advanced disease.

The aim of this prospective study is to report our experience in the multimodal management of locally advanced esophageal squamous cell carcinoma (LAESC; stage III cTNM), focusing on the results of chemoradiotherapy followed by surgery. These findings were compared to the results of a standard group of patients with locally advanced esophageal carcinoma (LAEC; stage III pTNM) treated in our center with surgery alone. Sixty-one patients with LAESC underwent preoperative chemoradiotherapy (5-fluorouracil + cisplatin) with concomitant 45 Gray radiotherapy in a 5-week course. Transthoracic esophagectomy was performed 4 to 5 weeks after the end of the neoadjuvant therapy. Thirty-eight patients underwent surgery, and 37 of them had resections (resectability: 97% in the multimodal group; 84% in the standard surgical series; p = 0.07). The R0 (complete) resection rate was 78% compared to 56% in the standard surgical group (p <0.03). Eleven patients had no residual tumor in the resected specimen (pathologic complete response: pCR: 30%). The operative mortality rate was 19% compared with 8.8% in the standard series. The overall median survival of the resected patients was 21 months, with a 5-year survival rate of 11% (14% in the surgical group; NS). The 3-year and 5-year survival rates were 34% for the pCR group and respectively 5% and 0% for the group with pathologic incomplete response (pIR; p <0.05). The median survival was 28 months for the pCR patients and 19 months for the pIR group. In this non-randomized trial, preoperative chemoradiotherapy in LAESC seems to increase the resectability and R0 resection rates, to allow a higher pCR rate and a longer survival only in the pCR group, at the expense of an inadequate increase in operative mortality. This multimodal treatment cannot be proposed as a standard procedure unless less toxic regimens are developed, increasing the benefits with better local and distant failure control and decreasing operative mortality.

Antimetabolites, Antineoplastic↗

PubMed2026

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 = 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 < 0.001) and molecular risk (HR: 7.1, P < 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 = 0.855; DFS, C-index = 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↗

PubMed1997

Multimodality treatment of thymoma: a prospective study.

BACKGROUND: Thymomas are a heterogeneous group of tumors. Treatment of invasive lesions is not well standardized. The aim of this study is to propose a clinicopathologically based protocol for multimodality therapy. METHODS: Between 1965 and 1988, we operated on 83 patients with thymoma who did not receive standardized adjuvant therapy. In 1989, on the basis of the retrospective analysis of the data, we started a multimodality therapy protocol and used it for 65 patients. Twelve patients had medullary thymoma (11 stage I and 1 stage II), 13 had mixed type (6 stage I and 7 stage II), and 40 had cortical thymoma (4 stage I, 11 stage II, 12 stage III, and 13 stage IV). We considered three groups. Group I (n = 18 patients), benign thymoma, included stage I and II medullary and stage I mixed thymomas; radical resection with no adjuvant therapy was performed. Group II (n = 22), invasive thymoma, included stage I and II cortical and stage II mixed thymomas; postoperative chemotherapy plus radiotherapy was always administered. Group III (n = 25), malignant thymoma, comprised stage III and IV cortical thymomas and stage III mixed thymomas; resectable stage III lesions were removed, and highly invasive stage III and stage IV lesions underwent biopsy, neoadjuvant chemotherapy, and surgical resection; postoperative chemotherapy and radiotherapy was administered to all patients. RESULTS: The 8-year survival rate for patients in stages I, II, III, and IV was 95%, 100%, 92%, and 68%, respectively. Patients with medullary thymoma had a 92% 8-year survival rate; those with mixed type, 100%; and those with cortical thymoma, 85%. Group I had an 8-year survival rate of 94%; group II, 100%; and group III, 76%. Survival was compared with that of patients operated on before 1989: differences were not significant for group I; survival improved in group II (100% versus 81%; p = not significant); and group III showed significant improvement (76% versus 43%; p < 0.049). CONCLUSIONS: Multimodality treatment with neoadjuvant chemotherapy and adjuvant chemotherapy plus radiotherapy may improve the results of radical resection and the survival of patients with invasive and malignant thymoma.

Adult↗

PubMed1999

Pleural space perfusion with cisplatin in the multimodality treatment of malignant mesothelioma: a feasibility and pharmacokinetic study.

INTRODUCTION: Malignant pleural mesothelioma is an ideal model for testing new locoregional multimodality approaches because of its aggressive local behavior. METHODS: This study was planned to investigate the feasibility, safety, and pharmacokinetics of a multimodality therapy including an operation, pleural space perfusion (60 minutes) with cisplatin (100 mg/m2), hyperthermia (41. 5 degrees C), and postoperative radiotherapy (55 Gy to chest wall incisions). The effects of the extent of resection and perfusion temperature on cisplatin pharmacokinetics were evaluated. Ten patients with epithelial or mixed, stage I or II, malignant pleural mesothelioma underwent the following procedures: group A (3 patients), pleurectomy/decortication and normothermic pleural space antineoplastic perfusion; group B (3 patients), pleurectomy/decortication and hyperthermic perfusion; and group C (4 patients), pleuropneumonectomy and hyperthermic perfusion. Operations were selectively applied depending on tumor extent. Platinum levels were serially measured by atomic absorption in systemic blood, perfusate, lung, and endothoracic fascia. RESULTS: The overall procedure was completed in every case, without any death or toxicity. No lung damage was demonstrated after treatment. Major complications included 1 wound infection and 1 diaphragmatic prosthesis displacement. The mean peak platinum plasma levels were reached within 45 to 60 minutes after perfusion was started. Systemic drug concentrations were greater after pleurectomy/decortication than after pleuropneumonectomy (P =.006). The local tissue/perfusate ratio of platinum concentrations tended to be higher after hyperthermic perfusion rather than normothermic perfusion. CONCLUSION: This multimodality approach is feasible, pharmacokinetically advantageous, and safe enough to undergo further clinical investigations.

Adult↗

PubMed1996

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↗

PubMed2001

Locally advanced primary breast cancer: medium-term results of a randomised trial of multimodal therapy versus initial hormone therapy.

We report the medium-term (median follow-up=52 months) results of a prospective randomised trial of multimodal therapy (neoadjuvant chemotherapy, Patey mastectomy, postoperative radiotherapy and adjuvant hormone therapy) (n=56) versus initial hormone therapy (n=52) for locally advanced primary breast cancer. Compared with multimodal therapy, initial hormone therapy was associated with reduced number of therapies for disease control (mean=3.6 versus 4.9) and mastectomy rate (31%). Multimodal therapy conferred better initial locoregional control and a longer disease-free interval. Nevertheless, there was no statistically significant differences in the rates of survival, metastasis and uncontrolled locoregional disease, as well as in the time to metastasis between the two therapy groups. Regardless of the therapy groups, oestrogen receptor positivity conferred a lower metastasis rate, better survival and locoregional control. Thus, initial hormone therapy may be a reasonable option for managing locally advanced primary breast cancer, especially for oestrogen receptor-positive tumours.

Adult↗

PubMed1997

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↗

PubMed1997

Demonstration of accuracy and clinical versatility of mutual information for automatic multimodality image fusion using affine and thin-plate spline warped geometric deformations.

This paper applies and evaluates an automatic mutual information-based registration algorithm across a broad spectrum of multimodal volume data sets. The algorithm requires little or no pre-processing, minimal user input and easily implements either affine, i.e. linear or thin-plate spline (TPS) warped registrations. We have evaluated the algorithm in phantom studies as well as in selected cases where few other algorithms could perform as well, if at all, to demonstrate the value of this new method. Pairs of multimodal gray-scale volume data sets were registered by iteratively changing registration parameters to maximize mutual information. Quantitative registration errors were assessed in registrations of a thorax phantom using PET/CT and in the National Library of Medicine's Visible Male using MRI T2-/T1-weighted acquisitions. Registrations of diverse clinical data sets were demonstrated including rotate-translate mapping of PET/MRI brain scans with significant missing data, full affine mapping of thoracic PET/CT and rotate-translate mapping of abdominal SPECT/CT. A five-point thin-plate spline (TPS) warped registration of thoracic PET/CT is also demonstrated. The registration algorithm converged in times ranging between 3.5 and 31 min for affine clinical registrations and 57 min for TPS warping. Mean error vector lengths for rotate-translate registrations were measured to be subvoxel in phantoms. More importantly the rotate-translate algorithm performs well even with missing data. The demonstrated clinical fusions are qualitatively excellent at all levels. We conclude that such automatic, rapid, robust algorithms significantly increase the likelihood that multimodality registrations will be routinely used to aid clinical diagnoses and post-therapeutic assessment in the near future.

Abdomen↗

PubMed2001

Urologic and sexual morbidity following multimodality treatment for locally advanced primary and locally recurrent rectal cancer.

AIMS: In the treatment of patients with locally advanced primary or locally recurrent rectal cancer much attention is given to the oncological aspects. In long-term survivors, urogenital morbidity can have a large effect on the quality of life. This study evaluates the functional outcome after multimodality treatment in these patient groups. PATIENTS AND METHODS: Between 1994 and August 1999, 55 patients with locally advanced primary and 66 patients with locally recurrent rectal cancer were treated with multimodality treatment: i.e. high-dose preoperative external beam radiation therapy, followed by extended surgery and intraoperative radiotherapy. The medical records of the 121 patients were reviewed. To assess long-term urogenital morbidity, all patients still alive, with a minimum follow-up of 4 months, were asked to fill out a questionnaire about their voiding and sexual function. Seventy-six of the 79 currently living patients (96%) returned the questionnaire (median FU 14 months, range 4-60). RESULTS: The questionnaire revealed identifiable voiding dysfunction as a new problem in 31% of the male and 58% of the female patients. In 42% of patients after locally advanced primary and 48% after locally recurrent rectal cancer treatment bladder dysfunction occurred. The preoperative ability to have an orgasm had disappeared in 50% of the male and 50% of the female patients, and in 45% of patients after locally advanced primary and in 57% after locally recurrent rectal cancer treatment. CONCLUSION: Multimodality treatment for locally advanced primary and recurrent rectal cancer results in acceptable urogenital dysfunction if weighed by the risk of uncontrolled tumour progression. Long-term voiding and sexual function is decreased in half of the patients. Preoperative counselling of these patients on treatment-related urogenital morbidity is important.

Adult↗

PubMedDate not supplied

Effect of preemptive multimodal analgesia for arthroscopic knee ligament repair.

BACKGROUND AND OBJECTIVES: Administration of analgesic medication before surgery, rather than at the completion of the procedure, may reduce postoperative pain. Similarly, administration of multiple analgesics, with different mechanisms of action, may provide improved postoperative pain control and functional recovery. The purpose of our study was to compare pain scores and intravenous opioid consumption after outpatient anterior cruciate ligament (ACL) reconstruction in patients who received a multimodal drug combination (intravenous [IV] ketorolac, intra-articular morphine/ropivacaine/epinephrine, and femoral nerve block with ropivacaine) either before surgery or immediately at the completion of the surgical procedure. METHODS: Forty patients presenting for same-day arthroscopic ACL repair using a semitendinosis tendon graft were included in this study. The patients were randomized to receive the following drugs either 15 minutes before skin incision or immediately after skin closure: (1) Ketorolac 30 mg IV. (2) Intra-articular injection of 20 mL ropivacaine 0.25% + morphine 2 mg and epinephrine 1:200,000. (3) Femoral nerve block with 20 mL ropivacaine 0.25%. Verbal pain scores were obtained in the postanesthesia care unit (PACU) and on postoperative days 1, 3, and 7. IV patient controlled analgesia (PCA) morphine consumption in the PACU was also recorded. RESULTS: Verbal pain rating scores were lower in group I (preemptive) for 2.0 hours after arrival in the PACU. There was no difference between groups in pain scores on postoperative days 1, 3, and 7. Mean IV PCA morphine consumption in the PACU was lower in group I (6.4 mg) versus group II (12.3 mg), P <.05. CONCLUSION: Preemptive, multimodal administration of our 3-component analgesic drug combination resulted in lower pain scores during the initial stay in the PACU unit and lower consumption of IV PCA morphine in the PACU. However, pain scores were similar in both groups on postoperative days 1, 3, and 7; thus, there was no measurable long-term advantage associated with preemptive multimodal drug administration.

Adult↗

PubMed1985

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↗

PubMed2026

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↗

PubMed2002

Long-term results with multimodal adjuvant therapy and liver transplantation for the treatment of hepatocellular carcinomas larger than 5 centimeters.

OBJECTIVE: To determine the long-term results of liver transplantation for hepatocellular carcinoma (HCC) measuring 5 cm or larger treated in a multimodality adjuvant protocol. SUMMARY BACKGROUND DATA: Transplant has been established as a viable treatment of HCC measuring less than 5 cm, but the results for larger tumors have been disappointing. Several studies have shown promising preliminary results when combining transplant with preoperative transarterial chemoembolization and/or perioperative systemic chemotherapy in the treatment of advanced HCC that is not amenable to resection. However, follow-up in the studies has been limited and the number of patients has been small. METHODS: Beginning in October 1991, all patients with unresectable HCC measuring 5 cm or larger, as measured by computed tomography, were considered for enrollment in the authors' multimodality protocol. Entry criteria required that all patients be free of extrahepatic disease based on computed tomography scans of the chest and abdomen and bone scan and have a patent main portal vein and major hepatic veins on duplex ultrasonography. Patients received subselective arterial chemoembolization with mitomycin C, doxorubicin, and cisplatin at the time of diagnosis, repeated as necessary based on tumor response. Patients received a single systemic intraoperative dose of doxorubicin (10 mg/m(2)) before revascularization of the new liver and systemic doxorubicin (50 mg/m(2)) every 3 weeks as tolerated, for a total of six cycles, beginning on the sixth postoperative week. RESULTS: Eighty patients were enrolled; 37 were eventually excluded, due mainly to disease progression while on the waiting list, and 43 underwent liver transplant. Mean pathologic tumor diameter was 5.8 +/- 2.7 cm. Median follow-up of surviving transplanted patients was 55.1 +/- 24.9 months. There were two (4.7%) perioperative deaths. Median overall survival was significantly longer in transplanted patients (49.9 +/- 10.42 months) than in those who were excluded (6.83 +/- 1.34 months). Overall and recurrence-free survival rates in transplanted patients at 5 years were 44% and 48%, respectively. A tumor size larger than 7 cm and the presence of vascular invasion correlated significantly with recurrence. Recurrence-free survival at 5 years was significantly higher for the 32 patients with tumors measuring 5 to 7 cm (55%) than the 12 patients with tumors larger than 7 cm (34%). CONCLUSIONS: A significant proportion of patients with HCC measuring 5 cm or larger can achieve long-term survival after liver transplantation in the context of multimodal adjuvant therapy. Patients with tumors measuring 5 to 7 cm have significantly longer recurrence-free survival compared with those with larger tumors.

Aged↗