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PubMed2004

Multimodality treatment of upper extremity bone and soft tissue sarcomas.

Management of soft tissue sarcomas requires a multidisciplinary approach with the help of a surgical-orthopedic oncologist, medical oncologist, radiation oncologist, pathologist, hand surgeon, and physiatrist/physical therapist. The indication and benefits of chemotherapy and radiation therapy for soft tissue sarcomas remain somewhat controversial.However, the encouraging results of studies using the most active chemotherapeutic agents gives credence to considering neoadjuvant chemoradiation therapy or postoperative adjuvant chemotherapy in this group of patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Multimodal therapy before liver transplantation for hepatocellular carcinoma.

BACKGROUND: : The use of orthotopic liver transplantation (OLT) for the treatment of patients with hepatocellular carcinoma (HCC) remains controversial because of the risk of both exclusion from the waiting list due to tumor progression and post OLT HCC recurrence. The aim of the present study was to evaluate the effect of an aggressive HCC treatment during the waiting list time on overall and recurrence-free survival of HCC transplanted patients in a single institutional study. METHODS: : Since 1991, 40 HCC patients joined the OLT-waiting list. Poorly differentiated HCC cases were excluded, while size and number of nodules were not considered as absolute selection criteria. In all, 90% of the study group had HCC treatment while on the waiting list (transarterial chemoembolization, percutaneous therapies, chemotherapy). RESULTS: : Only one patient (2.5%) was removed from the waiting list after developing neoplastic portal thrombosis 3 months after listing, while 33 (82.5%) underwent to OLT after a median waiting list time of 11 months (range 3-16 months). On histological examination, 42% of the group did not meet the "Milan criteria" and 42% were pTNM stages III and IV. The median follow-up was 42 months. The 5-year actuarial survival rate was 64% and recurrence-free survival was 91%. HCC recurred in only two patients (6%). CONCLUSIONS: : The use of routine pre-OLT tumor grading and of an aggressive HCC treatment during the waiting list, in our experience, resulted in a very low risk of pre OLT tumor progression leading to exclusion and of post OLT HCC recurrence.

Journal Article↗
PubMed2005

Multimodality treatments in the management of malignant pleural mesothelioma: an update.

Malignant pleural mesothelioma (MPM) is relatively unique among cancers because the local and regional disease rather than the systemic disease usually contributes to death. Because of its multifocal distribution in the chest, MPM progresses locally by compressing the lung, heart, and major vessels and causes death by cardiac tamponade and lung collapse physiology. The therapy for this aggressive local malignancy is currently inadequate. In most cases there is no sufficient time for systemic disease to develop or contribute to mortality. The first order of therapy in MPM is currently, as it has been for decades, to control effectively the tumor's locoregional spread and then deal with controlling the distant disease.

Combined Modality Therapy↗
PubMed2007

Using economic analysis to evaluate the potential of multimodality therapy for elderly patients with locally advanced pancreatic cancer.

PURPOSE: Development of new and expensive drugs with activity against pancreatic cancer has made economic considerations more relevant to treatment decision-making for advanced disease. Economic modeling can be used to explore the potential of such novel therapies and to inform clinical trial design. METHODS AND MATERIALS: We developed a Markov model to evaluate the cost-effectiveness of radiation plus fluorouracil (RT-FU) relative to no treatment in elderly patients with locally advanced pancreatic cancer (LAPC) and to determine the economic potential of radiation plus gemcitabine (RT-GEM), a novel regimen for this disease. We used the SEER-Medicare database to estimate effectiveness and costs supplemented by data from the literature where necessary. RESULTS: Relative to no treatment, RT-FU was associated with a cost-effectiveness ratio (ICER) of $68,724/QALY in the base case analysis. Compared with RT-FU, the ICER for RT-GEM was below $100,000/QALY when the risk of dying with the new regimen was <85% than with the standard regimen. However, >1,000 subjects would be necessary to demonstrate this level of efficacy in a randomized trial. The ICER of RT-GEM was most sensitive to utility values, and, at lower efficacy levels, to costs of gemcitabine and treatment-related toxicity. CONCLUSIONS: In elderly patients with LAPC, RT-FU is a cost-effective alternative to no treatment. The novel regimen of RT-GEM is likely to be cost-effective at any clinically meaningful benefit, but quality-of-life issues, drug acquisition, and toxicity-related costs may be relevant, especially at lower efficacy levels.

Aged↗
PubMed2025

Predicting the First Onset of Suicidal Thoughts and Behaviors in Adolescents Using Multimodal Risk Factors: A 4-Year Longitudinal Study.

OBJECTIVE: Suicide is one of the leading causes of death among youth worldwide, yet existing studies that aimed to predict the first onset of suicidal thoughts and behaviors (STB) included a limited number of data modalities and/or focused on adult populations. This study aimed to prospectively predict first-onset STB across 4-year follow-ups in adolescents using an existing STB history classification model that was previously applied to baseline data and a new machine learning model with 195 biopsychosocial features. METHOD: Participants were 7,503 unrelated adolescents (54.5% female, ages 9-11 years at baseline) from the multisite, longitudinal Adolescent Brain Cognitive Development (ABCD) Study. An existing baseline STB history classification model was applied to predict longitudinal first-onset STB in adolescents compared with healthy controls and clinical controls (individuals with a mental health disorder but no STB). A new elastic net logistic regression model with 195 features was trained on data from 14 sites (n = 5,220), and the resulting top 15 features were validated at 7 independent sites (n = 2,283). RESULTS: The previously developed model to classify STB lifetime history also prospectively predicted first-onset STB in adolescents with an area under the curve (AUC) [95% CI] of 0.73 [0.70, 0.75], p < .001, compared with healthy controls and AUC [95% CI] of 0.63 [0.60, 0.66], p < .001, compared with clinical controls. The newly trained model with top 15 features performed similarly with AUC [95% CI] of 0.73 [0.71, 0.76], p < .001, and AUC [95% CI] of 0.64 [0.60, 0.66], p < .001, for the same comparison groups. The most consistent predictors across models included female sex, sleep disturbances, and maladaptive home and school environments. CONCLUSION: The models predicted first-onset STB in adolescents with moderate accuracy. This study also confirmed the roles of well-established psychological risk factors for STB and identified several novel neurocognitive and brain imaging risk factors. Future studies should validate these models in large-scale diverse samples before clinical translation. PLAIN LANGUAGE SUMMARY: This study followed over 7,500 adolescents for 4 years and tested 2 machine learning models using psychological, social, and brain data to identify those at risk of experiencing suicidal thoughts or behaviors. Both models predicted first-time suicidal thoughts or behaviors with moderate accuracy. Key risk factors that were identified included being female, experiencing sleep problems, and negative home and school environments. DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. Diverse cell lines and/or genomic datasets were not available. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. We actively worked to promote sex and gender balance in our author group. One or more of the authors of this paper received support from a program designed to increase minority representation in science. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.

Adolescent↗
PubMed2004

2-Mercapto-5-benzimidazolesulfonic acid: an effective multimodal ligand for the separation of antibodies.

The report describes the use of 2-mercapto-5-benzimidazolesulfonic acid (MBISA) as a ligand for the separation of antibodies by chromatography. The ligand shows a relatively specific adsorption property for antibodies from very crude biologicals at pH 5.0-5.5. At this pH range most of other proteins do not interact with the resin especially when the ionic strength is similar to physiological conditions. Several characterization studies are described such as antibody adsorption in different conditions of ionic strength, pH and temperature. These properties are advantageously used to selectively capture antibodies from very crude feed stocks without dilution or addition of lyotropic salts. Demonstration was made that the adsorption mechanism is neither based on ion exchange nor on hydrophobic associations, but rather as an assembly of a variety of properties of the ligand itself. Binding capacity in the described conditions ranges between 25 and 30 mg/mL of resin. The sorbent does not co-adsorb albumin (Alb) and seems compatible with a large variety of feedstocks. Quantitative antibody desorption occurs when the pH is raised above 8.5. The final purity of the antibody depends on the nature of the feedstock, and can reach levels of purity as high as 98%. Even with very crude biological liquids such as ascites fluids, cell culture supernatants and Chon fraction II + III from human plasma fractionation where the number of protein impurities is particularly large, immunoglobumins G (IgG) were separated at high purity level in a single step.

Adsorption↗
PubMed2005

Capture of a monoclonal antibody and prediction of separation conditions using a synthetic multimodal ligand attached on chips and beads.

A synthetic ligand called 2-mercapto-5-benzimidazolesulfonic acid has been successfully used for the specific chromatographic capture of antibodies from a cell culture supernatant. Adsorption occurred at physiological ionic strength and pH range between 5.0 and 6.0, with some binding capacity variations within this pH range: antibody uptake increased when the pH decreased. With very dilute feedstocks, as was the case with the cell culture supernatant under investigation, it was found that the pH had to be slightly lowered to get a good antibody sorption capacity. To optimize separation conditions, a preliminary study was made using ProteinChip Arrays that displayed the same chemical functionalities as the resin. Arrays were analyzed using SELDI-MS. By this mean, it was possible to cross-over simultaneously different pH conditions at the adsorption and the desorption steps. Best conditions were implemented for preparative separation using regular lab-scale columns. At pH 5.2, antibody adsorption was not complete, while at pH 5.0 the antibody was entirely captured. pH 9 was selected at elution, rather than pH 8.0 or 10.0, and resulted in a complete desorption of antibodies from the column. Benefits of the prediction of separation conditions of antibodies on MBI beads using SELDI-MS were a significant reduction in analysis time and in sample volume. This was possible because the separation of IgG on the chip surface did mimic very well the separation on beads.

Adsorption↗
PubMed2006

Multimodality treatment of trigeminal neuralgia: impact of radiosurgery and high resolution magnetic resonance imaging.

This study was conducted to evaluate the two main surgical modalities, microvascular decompression (MVD) and gamma-knife radiosurgery (GK), the treatment of trigeminal neuralgia (TN) and outline for an algorithm for the selection of these procedures. The authors have identified distinct differences in the two treatment groups and formulated a scale that predicts the outcome and satisfaction of patients who underwent the procedures. This series included 34 TN patients treated in 2000 and 2001 with MVD (19) and GK (15). Patients with TN associated with tumor or multiple sclerosis were excluded. Each patient's age, past medical history, clinical features of pain or pre-operative pain grade, duration of TN, medications, and prior surgical procedures were recorded. Long-term results were assessed by a structured interview by telephone. Clinical outcome was classified as excellent (complete relief without medications and numbness), good (complete relief without medications), fair (> 50% relief or with substantial numbness and weakness), or poor (< 50% relief or treatment failure). Patient self-rated satisfaction score was rated on a scale of 1 (unsatisfied) to 10 (completely satisfied). Statistical analysis was performed by paired t-tests and anova with post-hoc analysis by the Tukey-Kramer method. The median follow-up was 17 months (18 months for MVD and 16 months for GK). The average age of MVD patients was 61 years compared to 74 years for GK patients (p = 0.0005). In both groups there was a female majority (68% for MVD and 60% for GK). The latency between first symptom of TN and treatment procedure was 3.0 years for MVD and 3.9 years for GK (p > 0.05). There was no significant difference in pain grade between the two groups. The average TN complexity grade was significantly different between the two groups (3.0 for MVD and 5.8 for GK) (p < 0.001). Average response to procedure for MVD was 3.4 (good) and 2.4 (fair) for GK (p = 0.017). The satisfaction outcome for MVD was 8.7 compared to 6.4 for GK (p = 0.02). There was a significant correlation (r = -0.818, p < 0.001) between TN complexity grade and response. Additionally, a significant correlation between TN complexity grade and patient satisfaction was found (r = -0.763, p < 0.0001). The data here support the treatment algorithm employed by the senior author (JFA) of this study. The TN complexity grade accurately correlates with the patient's response and satisfaction to the surgical procedure. This complexity grade may be useful for patient counseling when choosing between treatment options.

Adult↗
PubMed2005

The role of a more extensive surgical approach in the initial multimodality management of papillary thyroid cancer in children.

PURPOSE: Papillary thyroid cancer (PTC) in children is rare. The optimal initial surgical treatment remains controversial, given the generally favorable overall prognosis but high rate of cervical metastasis and local recurrence. Our objective was to examine the surgical outcomes of a policy of total thyroidectomy and routine selective lymph node dissection (SLND) as the initial surgical approach to children with PTC. METHODS: This is a retrospective cohort study comprising 14 children (age, < or =17 years) with PTC referred for thyroid surgery during the past 15 years. Clinical presentation, the surgical procedure, final pathology, lymph node involvement, complications, and recurrence rates are reported. RESULTS: There were 9 females and 5 males, with an average age of 12.5 years. Seven patients (50%) had clinically apparent cervical lymphadenopathy at the time of surgical referral. All subjects underwent total thyroidectomy, and 12 (86%) had SLND. Of the 12 who underwent SLND, 10 (83%) had nodal metastases. Temporary hypocalcemia was noted in 3 of the patients (21%), and 1 patient has required ongoing intermittent calcium supplementation. All patients are alive and well at follow-up with no clinical, biochemical, or radiological evidence of local recurrence. CONCLUSIONS: Total thyroidectomy with initial SLND is an appropriate surgical approach in children with PTC. It can be done without a significantly increased risk for permanent complications and may reduce the requirement for subsequent surgical intervention for local recurrence in this young population.

Adolescent↗
PubMed2006

Multimodal drug addiction treatment: a field comparison of methadone and buprenorphine among heroin- and cocaine-dependent patients.

AIMS: Our objective was to compare the effectiveness of buprenorphine (BUP) and methadone maintenance treatment in opiate-addicted patients in a clinical nonexperimental setting. DESIGN: We used a naturalistic observational prospective study of 24 months' duration. SETTING: Subjects were enrolled and treated at a drug addiction outpatient clinic of the National Health System Local Unit in Milan, Italy. PARTICIPANTS: Two hundred fifty-seven subjects meeting the DSM-IV criteria for opioid dependence and opioid-seeking substitutive pharmacological treatment participated in the study. INTERVENTION: One hundred twenty-one subjects received BUP at a mean daily dose of 11 +/- 6 mg (median = 8; range = 2-30) for a mean duration of 249 days. One hundred thirty-six subjects received methadone at a mean daily dose of 54 +/- 29 mg (median = 50; range = 4-140) for a mean duration of 267 days. MEASUREMENTS: The main efficacy parameters were treatment retention rates and illicit substance abuse, as assessed by urinalysis. FINDINGS: Retention rates were comparable in both treatment groups, but BUP-treated subjects had significantly lower rates of illicit opiate consumption (p < .0001). CONCLUSIONS: The results confirm that, in a nonexperimental clinical practice setting, BUP is as effective as methadone in the treatment of heroin dependence, with significantly better opiate abuse control, thus possibly allowing longer and more effective treatment programs with reduced relapse rates.

Adult↗
PubMed2006

Multimodality treatment of unresectable stage III non-small cell lung cancer: interim analysis of a phase II trial with preoperative gemcitabine and concurrent radiotherapy.

OBJECTIVE: We report the preliminary results of a phase II trial undertaken to determine the feasibility and efficacy of gemcitabine and concurrent radiotherapy in patients with inoperable stage III non-small cell lung cancer. METHODS: Between February 2001 and June 2003, a total of 46 patients (37 male and 9 female, median age 64 years) with clinical stage III non-small cell lung cancer (41 cIIIA and 5 cIIIB) were enrolled in a combined chemoradiation protocol with gemcitabine as the chemotherapeutic agent. Gemcitabine (350 mg/m2) was administered weekly for 5 consecutive weeks as a 30-minute intravenous infusion before radiotherapy (total dose 50.4 Gy, 1.8 Gy/d). Toxicity was routinely assessed. Those patients with disease judged to be resectable at restaging underwent surgery. RESULTS: Toxicity was moderate, with the exception of 1 grade 3 thrombocytopenia. All but 5 patients were available for restaging. No complete responses were observed. Thirty-four patients (82.9%) had partial responses, 5 (12.2%) had stable disease, and 2 (4.9%) had progressive disease. Twenty-nine of 46 patients (63%, 27 cIIIA and 2 cIIIB) underwent surgery. Radical resection was possible in all cases. Surgery included 17 lobectomies, 4 bilobectomies, and 8 pneumonectomies. There were no deaths. Morbidity was 13.8% (4/29). Pathologic downstaging to stage 0 or I was observed in 18 patients (39%, 18/46). After a median follow-up of 13 months (range 2-28 months), 24 of the patients who had undergone operation (86.2%) were alive, with a median disease-free survival of 16 months. Overall 2-year survival was 66.1%, with a significant difference between resected and unresected disease (82% vs 36%, P = .0002). CONCLUSION: The results of this induction trial confirm the feasibility and the efficacy of gemcitabine with concurrent radiotherapy.

Aged↗
PubMed2006

A multimodal perioperative plan for radical cystectomy and urinary intestinal diversion: effects, limits and complications of early artificial nutrition.

PURPOSE: We evaluated the effects of early parenteral and enteral postoperative nutritional support on the restoration of normal bowel function, on the protein depletion that follows cystectomy and on observed complications. MATERIALS AND METHODS: Immediate parenteral nutrition was initiated after surgery. It was progressively shifted to the enteral route through a needle catheter jejunostomy inserted at surgery. RESULTS: A total of 28 patients with a mean age of 74.2 years (range 55 to 82) were enrolled into the study. Disease was pathologically confined to the bladder in 22 patients, locally advanced in 3 and extravesical in 3. Urinary diversions included an ileocolonic pouch in 15 patients and an orthotopic ileal reservoir in 13. Of the 28 patients 15 (53.6%) completed the protocol, whereas 13 (46.4%) did not. Median time to peristalsis and spontaneous passage of flatus was postoperative day 2 (range 2 to 5) and median time to normal diet resumption was postoperative day 4 (range 3 to 8). No significant differences were observed between patients who completed the protocol and those who did not with regard to the restoration of normal bowel function, and total protein, serum albumin and lymphocyte count. Minor complications were observed in 9 patients and major complications developed in 4. CONCLUSIONS: Early postoperative artificial nutrition did not affect the return of bowel function or postoperative protein depletion. Different strategies for more effective nutritional support will be explored in further studies.

Aged↗
PubMed2004

Stage-III NSClC: multimodality therapy for inoperable tumours.

The combination of radiotherapy and chemotherapy (RCT) has improved the treatment results of patients with inoperable stage-III NSCLC in comparison to irradiation alone and is seen as the standard treatment at present. Concomitant RCT was significantly superior to sequential RCT in three of four studies, so that the simultaneous therapy sequence is seen today as the best modality. Nevertheless, the results, with median survival times of 15-18 months and a 5-year survival rate between 10 and 20%, are still not satisfactory so that further possibilities of optimisation are being looked for: --Can the results of concomitant RCT be improved by an induction chemotherapy or subsequent chemotherapy? --Is there an additional benefit of operative measures for tumours which through the application of RCT get operable? --What is the additional benefit of biological response modifiers applied together with RCT? --Is there a place for RCT of elderly patients or patients in poor general condition? The rationale as well as the initial results shall be discussed in this overview.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Surgery after multimodality treatment for non-small-cell lung cancer.

Neoadjuvant treatment for Locally advanced non-small-cell lung cancer (NSCLC) stage IIIA and IIIB promises higher resection rates because of a reduction of the primary tumour and sterilisation of mediastinal nodes ("downstaging"). In this study we analyse the perioperative course and the long-term survival of patients with trimodality treatment. Between 03/1991 and 12/2002, 392 patients with NSCLC underwent resection after induction treatment. Included were 266 males and 126 females, age 55.8 +/- 9 (28-74), of whom 218 were stage-IIIA patients, 174 were stage-IIIB patients. Induction treatment included 3 courses of chemotherapy with cisplatin/etoposide or cisplatin/paclitaxel, followed by one course of chemotherapy with cisplatin/etoposide as well as hyperfractionated accelerated radiotherapy of the primary tumour and the mediastinal nodes with 45 Gy, followed by surgery. Before induction treatment all patients underwent mediastinoscopy. In patients with N3 disease mediastinoscopy was repeated before surgery. Resections included 133 pneumonectomies (34%), 15 bilobectomies (4%), 55 sleeve lobectomies (14%), 168 lobectomies (42.5%), 6 segmentectomies (1,5%), and 15 explorative thoracotomies (4%). In-hospital mortality rates amounted to 4.6% (18 patients) while postoperative morbidity ran up to 46% (180 patients). Morbidity and mortality rates were significantly higher in patients with Karnofsky status lower than 80% and patients older than 65 years. Bronchopleural fistulas occurred in 16 patients (3.2%). The protection of the bronchial stump or anastomosis with viable tissue, like pericardial fat, proves to be a significant factor for the reduction of septic complications. For NSCLC, the 5- and 7-year survival rates were 36% and 31%, respectively, for stage IIIA, and 26% for stage IIIB. This intensive trimodality treatment proves to be feasible. Treatment-related toxicities are overall moderate and acceptable. Accurate cardiopulmonary evaluation before surgery and reinforcement of bronchial stump or anastomosis can contribute to reducing complications. Induction treatment demonstrated a "downstaging effect", so that a clear trend for organ-sparing resection was observed. Long-term survival rates for selected groups look very promising when compared to historical controls.

Adult↗
PubMed2006

Induction cisplatin-gemcitabine-paclitaxel plus concurrent radiotherapy and gemcitabine in the multimodality treatment of unresectable stage IIIB non-small cell lung cancer.

BACKGROUND: To evaluate feasibility and safety of induction three-drugs combination chemotherapy and concurrent radio-chemotherapy in stage IIIB NSCLC. PATIENTS AND METHODS: Patients with stage IIIB NSCLC were treated with three courses of induction chemotherapy, cisplatin 50 mg/m(2), paclitaxel 125 mg/m(2) and gemcitabine 1000 mg/m(2) on days 1,8 of every 21 day cycle. Patients without distant progressive disease were then treated with radiotherapy and concurrent weekly gemcitabine (250 mg/m(2)). Toxicity and response of radio-chemotherapy treatment have been assessed. RESULTS: Between Jan 01 and Nov 02, 46 patients were enrolled. Grade 3+ hematological and non-hematological toxicity during the induction phase were 41.3% and 13.1%, respectively. In 38 patients a Clinical Response or Stable Disease was recorded and these patients underwent to concurrent radio-chemotherapy. Grade 3+ hematological and non-hematological toxicities were 8.2% in this group. Further response was observed in 66% of patients. Overall median survival time was 17.8 months, with a 3-year survival rates of 23%. CONCLUSION: Three-drugs induction chemotherapy and concurrent radio-chemotherapy with weekly gemcitabine in locally advanced stage IIIB NSCLC is feasible and safe.

Adult↗