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PubMed1985

Multimodal approach (surgery, chemotherapy, and radiotherapy) in the treatment of advanced ovarian carcinoma.

Forty-five patients with advanced ovarian carcinoma without prior chemotherapy were treated with cisplatin-Adriamycin (doxorubicin) combination, 50 mg/m2 intravenously, for 11 cycles. Second-look operation (SLO) was performed in patients without evidence of disease at the end of chemotherapy. Abdominopelvic irradiation was administered to those found to have microscopic or minimal disease (tumor less than 2 cm) at SLO. Forty patients were evaluable. Chemotherapy induced complete response in 56.7% and partial response in 16.7%. In 25% of the reoperated patients, no tumor was found; 30% had microscopic disease; 25% had minimal disease; and 20% had larger tumors. Two-year survival rate was 45%. The residual tumor left at initial operation, the histologic grade, and the response to chemotherapy influenced survival. Toxicity was moderate. There were three treatment-related deaths (one due to sepsis, one due to cardiotoxicity, and one at SLO, respectively). Radiotherapy was poorly tolerated after chemotherapy. The median duration of follow-up was 21.5 months. Further follow-up is needed to study the long-term benefits of this multimodal approach.

Actuarial Analysis↗
PubMed1986

Recent results of multimodal therapy of gastric lymphoma.

The efficacy of multimodality treatment of gastric lymphoma was examined in a retrospective study of 46 patients treated at the Memorial Sloan-Kettering Cancer Center from 1971 to 1982. The principal treatment plan consisted of surgical resection of the gastric lymphoma (n = 36) where feasible, followed by radiation therapy of the whole abdomen (n = 23) with a boosting dose to the stomach-bed to 3700 cGy, and/or chemotherapy using mainly the CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) regimen as an adjuvant (n = 7), or CHOP plus other drugs for advanced disease. The median follow-up time of patients was 61 months (range, 30 months to 14 years). There was no operative mortality. No patient developed known relapse in the abdomen after resection and total abdominal irradiation, and none suffered relapses after adjuvant chemotherapy, for Stages I-E and II-E. At 5 years, the estimated survival rate after treatment was 95%, 78%, and 25%, respectively for Stages I-E (n = 20), II-E (n = 9) and IV (n = 17). The results for Stage I-E and II-E resectable tumors were significantly improved (P less than 0.05 and less than 0.1 respectively) over those of similar tumors treated in 1949 to 1970.

Adult↗
PubMed1991

The role of infection in the morbidity and mortality of patients with head and neck cancer undergoing multimodality therapy.

Cancer of the head and neck is a common cancer worldwide. The majority of patients present with locally advanced disease. Recently a great deal of improvement has been made in multimodality therapy of this disease, warranting more careful consideration of factors affecting quality of life, disease course, and treatment. Infection is clearly a factor. Analysis of 662 hospital admissions of 169 head and neck cancer patients was performed. A definite infection was documented in 86 febrile episodes, pneumonia contributed to 40%, bacteremia to 13%, skin and soft tissue infection to 12%, and tracheobronchitis to 10%. Among the evaluated risk factors, foreign bodies, specifically intravenous (IV) cannulae and gastrostomy tubes, race, performance status, alcohol intake, and nutritional status were statistically significant variables that predicted for or were associated with infection. Infection contributed to 44% of the deaths.

Adult↗
PubMed1991

Multimodality cisplatin treatment in nonresectable alpha-fetoprotein-positive hepatoma.

Twenty-eight patients with alpha-fetoprotein-positive (AFP+) nonresectable hepatoma have been enrolled in a new multimodality Phase I, II program. Induction therapy consisted of 50 mg/m2 intravenous cisplatin followed by 2100 cGy irradiation to the tumor volume in seven fractions over 10 days. Hepatic arterial infusion of 50 mg/m2 cisplatin (IA-CDDP) was then administered at monthly intervals. Twenty-one patients have completed induction and at least two cycles of IA-CDDP. Twelve-month cumulative survival was 52% for all 28 patients and 69% for the 21 patients completing induction and IA-CDDP. Median survival has not yet been reached. Response rate (complete and partial) was 36% overall and 48% among the 21 patients who completed treatment. The improved survival of the present series of patients as well as the minimal hematologic toxicity suggests possible further integration of new modalities for therapy.

Adult↗
PubMed1994

Paratesticular rhabdomyosarcoma: delayed effects of multimodality therapy and implications for current management.

BACKGROUND: The combined modalities of surgery, chemotherapy, and radiation therapy have greatly improved the survival rate in childhood paratesticular rhabdomyosarcoma, but the incidence of complications and late side effects is a cause for concern. METHODS: We reviewed the records of 18 patients treated for paratesticular rhabdomyosarcoma at St. Jude Children's Research Hospital between 1962 and 1989. Patients with Group I disease were treated with orchiectomy, retroperitoneal lymph node dissection, and multi-agent chemotherapy; more advanced cases also received radiation therapy with concurrent chemotherapy. RESULTS: Sequelae included esophageal and common bile duct stricture, inguinal nerve entrapment syndrome, and small bowel obstruction. Short stature was found in all children whose spines were irradiated via para-aortic fields (34-37 Gy) prior to puberty. Two of 18 patients died from treatment complications and one from progressive disease. CONCLUSIONS: Multimodality treatment offers an excellent prognosis in paratesticular rhabdomyosarcoma, but is associated with significant morbidity and mortality rates. A discussion of therapy components and their application to disease stages suggests possible approaches to optimizing treatment for this therapy-sensitive malignancy.

Adolescent↗
PubMed1994

Multimodal adjuvant treatment and liver transplantation for advanced hepatocellular carcinoma. A pilot study.

BACKGROUND: Orthotopic liver transplantation has been used in a large number of patients with primary liver cancer because it increases the possibilities of resection of large tumors. Despite isolated cases of prolonged survival, however, the results of liver transplantation for advanced tumors have been universally disappointing because of high rates of tumor recurrence. In an attempt to reduce the recurrence rate, a pilot study testing a multimodal adjuvant treatment in patients undergoing liver replacement for hepatocellular carcinoma was undertaken. METHODS: The treatment consisted of preoperative hepatic arterial chemoembolization (iodized oil, doxorubicin, and gelatin sponge) and radiotherapy (5 Gy in one fraction immediately before surgery), and postoperative systemic chemotherapy with mitoxantrone. Nine patients entered this study. The tumor was solitary in two cases (5 cm and 8 cm) and multifocal in seven cases (2-9 nodules, 3-9 cm). The postoperative TNM stages were II in one case, III in one case, and IVA in seven cases. RESULTS: Chemoembolization and radiotherapy were performed in seven cases each (five patients had both treatments). All patients underwent liver transplantation with conventional immunosuppression. One patient died of heart failure 4 days after surgery. The remaining eight patients received 4 to 10 courses of chemotherapy (mean 9). The main toxicity of chemotherapy was leucopenia. Two patients died of recurrence: one at 7 months and one at 11 months. Six patients are alive, five of them without evidence of disease, with a mean follow-up of 30 months (range 16-45) after liver transplantation. The 3-year actuarial survival is 64%. CONCLUSIONS: These results show that an aggressive adjuvant therapy can be used in association with liver transplantation in the treatment of advanced hepatocellular carcinoma without increased mortality and suggest that such a protocol could be effective in preventing tumor recurrence.

Adult↗
PubMed1978

A multimodal treatment approach for incarcerated alcoholics.

A multimodal milieu treatment approach for alcoholism was assessed in a prison setting by use of the MMPI. The participants had a mean age of 41, four prior incarcerations, and documented difficulty with alcohol abuse prior to their incarceration. Analysis of an A-B treatment design showed significant changes on the F, PT, ES (p less than .05), L, K, D, SI, and A (p less than .01) scales of the MMPI after 6 months of program participation. With the exception of the PD scale, all changes were seen as positive. It should be noted that the PD scale may not be the most appropriate indicator of positive behavioral changes in a prison setting.

Adult↗
PubMed1995

Subclinical neurotoxicity of mercury vapor revealed by a multimodality evoked potential study of chloralkali workers.

Pattern visual, brainstem auditory, and somatosensory evoked potential (EP) studies were performed on 26 chloralkali workers. The intensity of mercury vapor exposure in these workers was estimated from the individual working history. Mercury levels in blood, urine, and hair were determined with atomic absorption spectrometry. The EP findings were compared with those from individually matched normal subjects. In brainstem auditory and somatosensory EP studies, prolonged neural conduction times in the central nervous system (CNS) were found in workers exposed to mercury vapor. In the pattern visual EP study, mercury workers had higher interpeak amplitudes. Findings of this study suggested that chronic exposure to mercury vapor would affect the CNS functions. A multimodality EP study is a useful adjunct in evaluation of chronic mercury neurotoxicity, especially in an epidemiological study.

Adult↗
PubMedDate not supplied

An HPLC/mass spectrometry platform for the development of multimodality contrast agents and targeted therapeutics: prostate-specific membrane antigen small molecule derivatives.

The production of disease-targeted agents requires the covalent conjugation of a targeting molecule with a contrast agent or therapeutic, followed by purification of the product to homogeneity. Typical targeting molecules, such as small molecules and peptides, often have high charge-to-mass ratios and/or hydrophobicity. Contrast agents and therapeutics themselves are also diverse, and include lanthanide chelates for MRI, (99m)Tc chelates for SPECT, (90)Y chelates for radiotherapy, (18)F derivatives for PET, and heptamethine indocyanines for near-infrared fluorescent optical imaging. We have constructed a general-purpose HPLC/mass spectrometry platform capable of purifying virtually any targeted agent for any modality. The analytical sub-system is composed of a single dual-head pump that directs mobile phase to either a hot cell for the purification of radioactive agents or to an ES-TOF MS for the purification of nonradioactive agents. Nonradioactive agents are also monitored during purification by ELSD, absorbance and fluorescence. The preparative sub-system is composed of columns and procedures that permit rapid scaling from the analytical system. To demonstrate the platform's utility, we describe the preparation of five small molecule derivatives specific for prostate-specific membrane antigen (PSMA): a gadolinium derivative for MRI, indium, rhenium and technetium derivatives for SPECT, and an yttrium derivative for radiotherapy. All five compounds are derived from a highly anionic targeting ligand engineered to have a single nucleophile for N-hydroxysuccinimide-based conjugation. We also describe optimized column/mobile phase combinations and mass spectrometry settings for each class of agent, and discuss strategies for purifying molecules with extreme charge and/or hydrophobicity. Taken together, our study should expedite the development of disease-targeted, multimodality diagnostic and therapeutic agents.

Antigens, Surface↗
PubMed2002

Results of multimodality therapy for squamous cell carcinoma of maxillary sinus.

BACKGROUND: A wide variety of modalities, including surgery, radiation therapy, and chemotherapy, alone or in combination, have been used for the treatment of squamous cell carcinoma (SCC) of the maxillary sinus to obtain better local control and maintain functions. However, there is still much controversy with regard to the optimum treatment. METHODS: From 1987 to 1999, 33 patients with SCC of maxillary sinus were treated at the Department of Otolaryngology-Head and Neck Surgery, University of Tokyo Hospital. The treatment consisted of 30-40 grays (Gy) of preoperative radiotherapy with concomitant intraarterial infusion of 5-fluorouracil and cisplatin followed by surgery and 30-40 Gy of postoperative radiotherapy, for tumors without skull base invasion. For tumors invading the skull base, preoperative systemic chemotherapy with or without radiotherapy was performed, instead of intraarterial chemotherapy, then followed by skull base surgery. The surgical procedures varied according to the extent of tumor. Results were compared with those of the 108 patients treated in our hospital from 1976 to 1982. RESULTS: Partial maxillectomy was performed in 2 T2 patients and 12 T3 patients. Total maxillectomy was performed in 1 T2 patient, 3 T2 patients, and 7 T4 patients. Skull base surgery was performed in eight T4 patients. Orbital content and hard palate were preserved in 22 patients and 18 patients, respectively. The overall 5-year survival rates were 86% in T 3 patients and 67 % in T4 patients, respectively. CONCLUSIONS: Our multimodal treatment has provided favorable local control and survival outcome with good functional results.

Adult↗
PubMed2002

Multimodal intensification therapy for previously untreated advanced resectable squamous cell carcinoma of the oral cavity, oropharynx, or hypopharynx.

BACKGROUND: An intensified treatment regimen for previously untreated Stage III and IV resectable oral cavity, oropharyngeal, or hypopharyngeal squamous cell carcinoma was analyzed to assess disease control, patient compliance, and toxicity. METHODS: Forty three patients with previously untreated, advanced, resectable squamous cell carcinoma of the oral cavity, oropharynx, or hypopharynx were enrolled in a prospective Phase II institutional clinical trial at a tertiary care comprehensive cancer center. This regimen was a continuum of multimodal treatment in a contracted time interval. It included preoperative slightly accelerated hyperfractionated radiotherapy with concurrent cisplatin, followed immediately with surgery and intraoperative radiotherapy, and completed with early postoperative weekly paclitaxel (beginning on Day 6 after surgery), two additional cisplatin cycles, and concurrent once daily radiotherapy beginning on Day 28 after surgery. RESULTS: The current trial was designed to reduce the toxicity of the systemic therapy while maintaining or improving locoregional/distant disease control and patient compliance. There were 43 patients enrolled, and the range of time at risk was 2.6 to 24.7 months (median, 14.6 months). Of the 43 registered patients, 43 were evaluable. The locoregional (100%) and systemic (93%) disease control rates were excellent, with low rates of patient noncompliance (21%) and reduced levels of toxicity. CONCLUSIONS: An intensive treatment regimen that improves disease control and treatment compliance is clearly feasible for this patient population. Future plans include modifications to continue to reduce toxicity and expansion to a multi-center Phase II trial to determine if the single institutional results can be duplicated.

Adult↗
PubMed2002

Brain metastases in locally advanced nonsmall cell lung carcinoma after multimodality treatment: risk factors analysis.

BACKGROUND: Brain metastases (BM) are frequent sites of initial failure in patients with locally advanced nonsmall cell lung cancer (LAD-NSCLC) undergoing multimodality treatments (MMT). New treatment and follow-up strategies are needed to reduce the risk of BM and to diagnose them early enough for effective treatment. METHODS: The incidence rate of BM as the first site of recurrence in 112 patients with LAD-NSCLC treated with the same MMT protocol was calculated. The influence of patient, disease, and treatment-related factors on the incidence of BM and on the time-to-brain recurrence (TBR) was analyzed. RESULTS: BM as the first site of failure was observed in 25 cases (22% of the study population and 29% of all recurrences). In 18 of those cases, the brain was the exclusive site of recurrence. Median TBR was 9 months. The 2-year actuarial incidence of BM was 29%. Central nervous system (CNS) recurrence was more common in patients younger than 60 years (P = 0.006) and in whom bulky (> or = 2 cm) mediastinal lymph nodes were present (P = 0.02). TBR was influenced by age (P = 0.004) and by bulky lymph node disease (P = 0.003). Multivariate analysis confirmed the prognostic role of age, whereas the presence of clinical bulky mediastinal lymph nodes was of borderline significance. CONCLUSIONS: Our study confirmed a high rate of BM in patients with LAD-NSCLC submitted to MMT. Most of these CNS recurrences were isolated and occurred within 2 years of initial diagnosis. Age younger than 60 years was associated with an increased risk of BM and reduced TBR, whereas the presence of clinical bulky mediastinal lymph nodes was of borderline significance. Although our data require further validation in future studies, our results suggest that additional trials on prophylactic cranial irradiation and on intensive radiologic follow-up should focus on these high-risk populations.

Adult↗
PubMed2004

Central nervous system metastases in patients with high-risk breast carcinoma after multimodality treatment.

BACKGROUND: The current study was performed to determine the incidence of central nervous system (CNS) metastases and to examine associated disease characteristics in a group of patients with locally advanced breast carcinoma (LABC) or inflammatory breast carcinoma (IBC) treated at The University of Texas M. D. Anderson Cancer Center (Houston, TX). METHODS: Seven hundred sixty-eight patients treated with multimodality therapy between 1982 and 2000 in any of 6 neoadjuvant trials were eligible for the current study. Five hundred ninety-two patients (77%) had LABC, and 176 (23%) had IBC. CNS disease was defined as the presence of brain metastases or leptomeningeal disease. Time to detection of CNS disease and overall survival were estimated using the Kaplan-Meier product-limit method, and differences were evaluated using log-rank tests. RESULTS: The median patient age was 48 years. Most tumors were classified as T4 lesions (58%) and exhibited lymph node involvement (78%). Fifty-one percent of all tumors had positive hormone receptor status. At a median follow-up duration of 9.5 years, 61 patients (8%) had developed CNS metastases, with the CNS representing the first site of recurrence for 38 of these 61 (63%). Characteristics associated with the development of CNS metastases over time included negative hormone receptor status (P = 0.03), Grade 3 disease (P = 0.01), and larger tumor size (P = 0.02). The median time to detection of CNS metastases was 2.3 years. Ten patients (16%) remained alive after treatment for CNS metastases. The median survival from the time of diagnosis of CNS metastases was 8 months. CONCLUSIONS: CNS metastases from breast carcinoma were relatively uncommon and were strongly associated with more aggressive clinical presentation. Survival from the time of diagnosis of such metastases generally was short.

Antineoplastic Agents↗
PubMed1990

Morphological and physiological characterization of small multimodal ocellar interneurons in the American cockroach.

The morphology and physiology of small multimodal ocellar interneurons (SM-neurons) have been examined in the cockroach Periplaneta americana. The SM-neuron is monopolar with its cell body in the tritocerebrum near the esophagus. Its axon ascends to the protocerebrum and extends into the ocellar neuropil through the ocellar tract and the ocellar nerve. The axon sends a long collateral process towards the optic tract. The SM-neuron responded with spike discharges to various sensory stimuli. The collateral and many side branches along the axon in the deutocerebrum appear to be input regions from those sensory afferents. Cercal stimulation triggered most effectively a train of spikes in the SM-neuron: some of seven giant axons in the ventral nerve cord were involved in this pathway. Cercal stimulation also evoked depolarization in the large second order ocellar neurons (L-neurons). A possible neural connection between SM-neurons and L-neurons was examined pharmacologically. Interaction of ocellar illumination and cercal stimulation in the L-neuron was also examined. These data are discussed in relation to the ocellar function of cockroaches and in comparison with data obtained in other insects.

Animals↗
PubMed1998

Multimodal application of lectin affinity electrophoresis of alpha-fetoprotein.

Multimodal application of lectin affinity electrophoresis of alpha-fetoprotein (AFP) glycoforms is reviewed. Crossed affinity immunoelectrophoresis developed by Bøg-Hansen and others was extended to tandem-lectin affinity electrophoresis by tandem lining of two different lectin gels and to mixed-lectin affinity electrophoresis. By introducing an antibody-affinity blotting technique for detection of separated glycoforms of AFP, several two-dimensional combinations of lectin affinity electrophoresis became possible: two different lectins for the first and second dimension electrophoresis, lectin-gradient affinity electrophoresis, and electrophoretic separation of lectin isoforms in the first-dimension electrophoresis, followed by affinity electrophoresis against the separated lectin isoforms. Usefulness of the different modalities of lectin affinity electrophoresis for several analytical purposes has been described.

Humans↗
PubMed2006

Squamous cell carcinoma of the buccal mucosa: an aggressive cancer requiring multimodality treatment.

BACKGROUND: In our clinical practice, we have observed a high incidence of locoregional failure in squamous cell carcinoma (SCC) of the buccal mucosa. We analyze our treatment results of this cancer and compare these results with those in the literature. We intend to define the pattern and incidence of failure of buccal cancer and provide information for the design of a better multimodality treatment. METHODS: During the period from 1983 through 2003, 121 previously untreated patients with M0 stage SCC of the buccal mucosa were treated with a curative intent at our hospital. Twenty-seven patients received surgery alone, 36 had radiotherapy alone, and 58 underwent surgery plus postoperative radiotherapy. RESULTS: The 5-year locoregional control, overall survival, and cause-specific survival rates for all patients were 36.3%, 34.3%, and 36.9%, respectively. The locoregional recurrence rate was 57% for all patients, with 80% occurring in the primary site alone. Patients with T1-2N0 disease who received surgery alone still had a high local recurrence incidence of 41%. For patients with locally advanced disease, surgery plus postoperative radiotherapy achieved better overall survival and locoregional control rates than surgery alone or radiotherapy alone. T classification was the only prognostic factor affecting locoregional control and survival in the surgery alone group, whereas N classification and skin invasion predicted a poorer survival for the surgery plus postoperative radiotherapy group. CONCLUSIONS: SCC of the buccal mucosa is an aggressive cancer with a high locoregional failure rate even in patients with T1-2N0 disease. Possible reasons include inadequate treatment and an intrinsically aggressive nature. Postoperative radiotherapy has resulted in a better locoregional control rate for patients with T3-4 or N+ disease and should also be considered for patients with T1-2N0 disease for whom adjuvant therapy after radical surgery currently is not recommended by most guidelines.

Adult↗
PubMedDate not supplied

Failure at the primary site following multimodality treatment in advanced head and neck cancer.

Recurrence at the primary site is an important cause of morbidity and mortality in head and neck cancer. In patients with stages III and IV disease treated surgically at Memorial Sloan-Kettering Cancer Center between 1960 and 1970, cancer recurred at the primary site in 39% even when the margins had been deemed satisfactory, and in 73% when the margins were unsatisfactory. Between 1975 and 1980, we treated 114 previously untreated patients with stages III and IV epidermoid carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx with a combination of surgery and postoperative radiation therapy. Twenty-seven patients also received preoperative chemotherapy. One hundred seven patients were evaluable for disease control at the primary site by the combined treatment. Cancer recurred at the primary site in 6 patients, including 2% of 47 patients whose surgical margins had been satisfactory and 10.5% of 60 patients whose surgical margins had been unsatisfactory. Of the latter, recurrence was seen in 5% of the 25 patients whose margins were less than 5 mm but were microscopically uninvolved, and in 15% of the 35 patients whose margins were microscopically involved by cancer. Comparison of these data with our historical control group suggests a decrease in the failure rate at the primary site with multimodality treatment. However, it still appears important to secure microscopically negative margins for the best results.

Antineoplastic Agents↗
PubMedDate not supplied

Failure in the neck following multimodality treatment for advanced head and neck cancer.

Failure in the neck is an important cause of morbidity and mortality in head and neck cancer. Patients who underwent therapeutic or elective radical neck dissection at Memorial Sloan-Kettering Cancer Center between 1960 and 1966 developed recurrence of cancer in the dissected neck in 36.5% of the cases when metastatic carcinoma was present in the cervical lymph nodes at one level, and in 71.3% when metastases were present at multiple levels. Between 1975 and 1980, we treated 114 previously untreated patients with stages III and IV epidermoid carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx with the combination of surgery and elective postoperative radiation therapy. Of these, 106 patients underwent radical neck dissection and 94 were proven to have metastatic carcinoma in the neck. Eleven patients developed recurrences in the neck. Recurrence developed in 16% of 19 patients with metastases at one level, and in 13% of 75 patients with metastases at multiple levels. For 53 patients, radiation therapy was started within 6 weeks after neck dissection and only 2% of them developed recurrence in the neck; for 41 patients, radiation therapy started later than 6 weeks and 29% of them developed recurrence (P less than 0.01). Comparison of these data with our historical control group suggests a decrease in the number of failures in the neck when a multimodality treatment is used. It appears, however, that irradiation must be started within 6 weeks after surgery for the best results.

Carcinoma, Squamous Cell↗