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PubMed1995

A versatile system for multimodality image fusion.

This paper presents a versatile system for registering and visualizing computed tomography and magnetic resonance images. The system utilizes a semi-automatic, surface-based registration strategy which has proven useful for registering a number of different anatomical structures. A triangular mesh approximates surfaces in one image set while a set of surface points is used as a surface approximation in the other set. A non-linear optimization procedure determines the transformation that minimizes the total sum-squared perpendicular distance between triangles of the mesh and surface points. This system has been used without modification to successfully register images of the brain, spine and calcaneus.

Brain↗
PubMed2001

Imaging molecular structure and physiological function of gap junctions and hemijunctions by multimodal atomic force microscopy.

Gap junctions are specialized plasma membrane structures that join neighboring cells via specialized intercellular ion channels (hemichannels) and provide a direct pathway for cell-cell communication. They presumably mediate regulation of growth, transmission of developmental signals, coordination of muscle contraction, and maintenance of metabolic homeostasis. Hemichannels are also present in the non-junctional regions of the cell plasma membrane and they provide a direct pathway for communication between the cytoplasm and the extracellular region. Recent studies suggest that gap junctional communication is much more complex than previously anticipated, in terms of both its structure as well as its activity. While the mechanism of gap junction activity is being studied extensively, their quaternary structure, assembly, and conformational changes underlying gating of their activity as well as their physiological role are poorly understood because, due to their complex structure, these junctions are less amenable to existing techniques for high-resolution three-dimensional structure-function analyses. Atomic Force Microscopy (AFM) images molecular structure of biological specimens in an aqueous environment, allows on-line perturbations, and can be coupled with electrophysiological, biochemical, and other microscopic techniques. The present review examines the potential of AFM application for the study of the molecular structure of hydrated, native gap junctions and hemijunctions as well as their physiological functions. Special attention is paid to new, complementary, or provocative findings from AFM studies of both vertebrate and invertebrate gap junctions and hemijunctions.

Animals↗
PubMed1977

Blindness during remission in two patients with acute lymphoblastic leukemia: a possible complication of multimodality therapy.

Two patients with acute lymphoblastic leukemia treated on the same protocol became blind during complete remission. Therapy consisted of systemic combination chemotherapy, prophylactic central nervous system irradiation and monthly intrathecal cytosine arabinoside. Eight months after CNS irradiation visual acuity in both patients began to decrease. Meningeal leukemia in the area of the chiasm was suspected but despite additional radiotherapy, steroids and continued intrathecal therapy, both patients were blind within 6 months. Numerous lumbar punctures were negative for leukemic cells. Extensive investigation, including craniotomy in one case, failed to reveal the cause of blindness. Biopsy of the optic nerve in one case was compatible with radiation toxicity. We postulate that potentiation of radiation toxicity to the optic nerves and chiasm by systemic chemotherapy, intrathecal chemotherapy, or both, may have led to blindness. The patients continue in complete hemotologic and CNS remission 12 and 29 months after becoming blind.

Acute Disease↗
PubMed1977

Acute and late effects of multimodal therapy on normal tissues.

The increasing use of combined radiation, chemotherapy, and surgery had led to an increased incidence of acute and late complications. The complications are, in general, similar to those seen with each modality alone, but occur with increased incidence. Enhanced effects of combined radiation and surgery are modest in number and consist primarily of problems with wound healing and fibrosis, as well as late gastrointestinal damage. Combinations of radiotherapy and chemotherapy have shown a greater degree of enhanced acute and late reactions. Drugs, such as actinomycin-D and Adriamycin, are particularly dangerous if the marked enhancement of radiation effects caused by the drugs in almost all organs is not appreciated and the radiation dose not adjusted accordingly. Proper selection of drugs can lead to enhanced local control by radiotherapy and/or surgery, as well as eradication of microscopic distant metastases, without increased normal tissue injury. Late induction of malignancy can occur with either radiation or chemotherapy alone and, in some cases, this appears to be enhanced when they are combined.

Antineoplastic Agents↗
PubMed1980

Multimodality therapy for medulloblastoma.

Eight patients with recurrent medulloblastoma were treated with a chemotherapy regimen consisting of vincristine, BCNU, dexamethasone and intrathecal and intermediate dose intravenous methotrexate (500 mg/m2). Five also received local low dose radiotherapy (RT). All 8 patients responded to treatment; 6 completely and 2 partially. These latter 2 were in their second and third recurrences. Three remain in remission. The median duration of response was 18.8 months, and median time from start of chemotherapy to death was 32 months using the Kaplan-Meier technique. In addition, 9 other patients with newly diagnosed medulloblastoma were treated with craniospinal radiation and the same adjuvant chemotherapy as above. The first 5 patients also received intraventricular methotrexate and/or intravenous BCNU during radiotherapy. The toxicity in the 5 patients was very severe. There were three toxic deaths, one death from cancer; one patient survives disease-free, but he is demented. With the discontinuance of intraventricular methotrexate and the postponement of myelo-suppressive chemotherapy until after the completion of radiotherapy, the regimen has been well tolerated. All 4 patients treated this way remain alive, well, and disease-free at intervals up to 36 months. We conclude that recurrent medulloblastomas are sensitive to multiagent chemotherapy and that prolonged remissions may occur. With primary adjuvant chemotherapy, extreme caution with myelo-suppressive drugs must be exercised during the period of craniospinal radiotherapy. We also do not recommend the use of intraventricular methotrexate. When these two criteria were followed, the preliminary results with adjuvant chemotherapy appear encouraging.

Adolescent↗
PubMed1980

Retroperitoneal rhabdomyosarcoma in children. Results of multimodality therapy.

The clinical course of 18 consecutive children treated for primary retroperitoneal rhabdomyosarcoma was reviewed. At diagnosis, 8 patients had regional unresected tumor and 10 patients had disseminated tumor, including 3 patients with documented bone marrow infiltration by tumor. Following combined modality therapy, 14 of 18 patients achieved a greater than 50% tumor response (11 complete and 3 partial responses); 4 patients failed to respond and died of progressive disease within eight months of diagnosis. Among the 14 patients responding, 7 patients had subsequent reextension of active tumor three to 16 months (median, 9 months) following the onset of therapy. Three of the 7 remaining patients died of treatment complications, 2 of intestinal obstruction and 1 of disseminated histoplasmosis, within the first year of therapy and at post-mortem examination had no demonstrable tumor. Four patients are alive and free of active tumor for 10+, 10+, 32+ and 33+ months from diagnosis. Treatment complications have included hematopoietic depression, mucositis, enteritis, intestinal obstruction, excessive weight loss, malnutrition, and life-threatening infection. These results illustrate limitations in current combined modality therapy of retroperitoneal rhabdomyosarcoma and the necessity for future treatment modifications to both reduce morbidity and to improve survival.

Adolescent↗
PubMed1980

The evolution of primary multimodality treatment in resectable breast cancer.

Based on both laboratory and clinical data, two major prospective randomized clinical trials were initiated in 1972 and 1973 by the NSABP and the Instituto Nazionale Tumori, of Milano, Italy, under the sponsorship of the National Cancer Institute, to test the value of administering chemotherapy to patients with Stage II breast cancer in the postoperative period. With a follow-up time of nearly five years, both studies continue to demonstrate a significantly prolonged disease-free interval for treated premenopausal women. The Milano trial also indicates an increase in survival from 74% to 90% in the treated group of premenopausal women. A recent analysis of the postmenopausal women treated in the Milano study show that those treated patients who received 75% of the calculated drug dose have significantly prolonged disease-free intervals. These positive results from these trials and byproducts of other basic and clinical research, particularly the value of the estrogen receptor as a prognostic factor of disease-free interval survival and possible treatment selector, have stimulated the scientific community to undertake additional adjuvant therapy studies. The design and rationale for these subsequent studies are discussed. Preliminary indications exist that these trials will lead to a reduction in the national mortality and the overall economic impact from this disease will be lessened within the next five years. Based on the positive results of these studies, rationale currently exists for designing clinical trials that have the potential to extend similar benefit to the 60,000 patients with Stage I disease.

Adult↗
PubMed1982

Effective multidrug, multimodality consolidation therapy of adult acute lymphocytic leukemia: a preliminary report.

Twelve of 13 adult patients with acute lymphocytic leukemia, acute undifferentiated leukemia, or convoluted T-cell lymphoma (T-cell ALL) who were treated with Adriamycin, vincristine, and prednisone achieved a complete remission. An intensive consolidation regimen was administered. This regimen included Cytosine Arabinoside, L-asparaginase, and multiple courses of CHOP (cyclophosphamide, Adriamycin, vincristine, and prednisone). In addition, cranial irradiation and intrathecal methotrexate were administered. By actuarial estimate, 81% of previously untreated patients who achieved a complete remission will remain in remission for more than two years.

Adult↗
PubMed1982

Multimodality therapy in the management of angiosarcoma of the breast.

Five patients with angiosarcoma of the breast were treated with surgery, radiotherapy and an adjuvant Adriamycin containing regimen. Two patients remain disease-free at 38+ and 20+ months. The median survival of previously reported cases is 22 months with only five patients disease-free at five years. Possible hormonal influences in the etiologic cause of angiosarcoma of the breast are discussed and the importance of early diagnosis and treatment in these relatively young patients is emphasized.

Adult↗
PubMed1983

Medulloblastoma. The identification of prognostic subgroups and implications for multimodality management.

For 43 medulloblastoma patients who had five-and ten-year actuarial survival rates of 56%, prognostic factors of statistical significance included: T-stage (82% T1,2 versus 46% T3,4; P less than 0.02), M-stage (63% M0,1 versus 0% M2,3; P less than 0.03), and histopathologic tumor score (TS, based upon necrosis, desmoplasia, cytoplasmic processes, and mitoses) (81% TS less than or equal to 5 versus 41% TS greater than or equal to 6; P less than 0.05). Posterior fossa local control rates were also function of T-stage (90% T1,2 versus 38% T3,4) and TS (83% TS less than or equal to 5 versus 38% TS greater than or equal to 6). Combining TS with T-stage, patients fell into three prognostic and local control groups, which may have different future management implications: Small (T1,2) tumors of favorable (TS less than or equal to 5) histology had a 92% ten-year actuarial survival rate with 100% (8/8) local control; no change from current management is suggested. For the intermediate prognosis group (T1,2-TS greater than or equal to 6 or T3,4-TS less than or equal to 5 with 67% and 70% survival, respectively), increasing the irradiation dose alone may improve survival because these tumors exhibited an irradiation dose-response relationship. However, it is the poor prognosis group (T3,4-TS greater than or equal to 6 with 42% survival) which might be suitable for future adjuvant chemotherapy or radiosensitizer trials since there is no evidence that higher irradiation doses improve local control. This article identifies prognostic subgroups based on histologic type and TM staging in medulloblastoma patients which potentially may be utilized to improve therapeutic results, and confirms the value of staging patients with central nervous system malignancies.

Adolescent↗
PubMed1983

Ten years' experience with a multimodality treatment of advanced stages of rectal cancer.

Patients with inoperable rectal cancer have a remote chance of 5-year survival. In an attempt to improve this poor prognosis a combined radiochemotherapeutic regimen in a split form followed by long term chemotherapy maintenance was used in their management. From January 1971 until December 1980, three categories of patients were so treated. 100 Patients with an inoperable rectal primary (IP) or locally recurrent after anterior resection (LR) with no evidence of distant metastases; 71 patients with pelviperineal recurrences after rectal amputation (PPR); and 28 patients with primary rectal cancer and asymptomatic liver metastases (PALM). Side effects were tolerable and could be medically controlled. The local response rates in the three groups, respectively, were 79%, 85% and 85%. The median duration of this response lasted 25, 16 and 14 months, respectively, after which there was local progression of disease. The median survival rates were 19, 19 and 13 months, respectively. None of the PALM group lived for more than 30 months, while there were 20% 5-year survivors in the IP-LR group and 15% in the PPR group. The incidence of distant metastases in these last two groups were 20% and 50% at 5 years, respectively, while incidence of late complications was about 10%. This regime offers a good palliative measure with a possible 15% to 20% chance of long-term disease-free survival.

Adult↗
PubMed1984

Multimodality therapy of localized unresectable pancreatic adenocarcinoma.

Eighty-eight patients with localized unresectable carcinoma of the pancreas were treated at Thomas Jefferson University Hospital between 1974 and 1981. Four treatment regimens were used which were sequential modifications of the technique based on the experience in the preceding group of patients. Each treatment changed the course of the disease, and as patterns of failure were identified, the treatment was altered to deal with them. Initially, all patients were treated with external beam radiation. Subsequently, Iodine-125 implantation was added to improve local control; low-dose preoperative radiotherapy to reduce the risk of peritoneal seeding; and adjuvant chemotherapy to reduce the risks of distant metastases. The addition of 125I implantation increased the local control from 22% to 81%, but did not increase the median survival, which was unchanged from 7 months. The addition of adjuvant chemotherapy increased the median survival from 7 months to 14 months, but had no impact on the control of the pancreatic tumor. Adjunctive chemotherapy and low-dose preoperative radiotherapy appear synergistic in reducing the risk of peritoneal seeding. The combination of 125I implantation, external beam radiation, and adjunctive chemotherapy is safe and effective. This regimen produces excellent local control with acceptable morbidity. This regimen produced a 30% survival at 18 months. The patterns of failure among these patients suggest future modifications of the technique.

Adenocarcinoma↗
PubMed1985

Acute non-lymphocytic leukemia following multimodality therapy for retinoblastoma.

The genetic form of retinoblastoma carries a high risk of secondary malignant neoplasm, apparently not related to the use of chemotherapy. A child with unilateral non-genetic retinoblastoma who had received chemotherapy and radiation therapy and developed acute non-lymphocytic leukemia (ANLL) is reported. The occurrence of ANLL and retinoblastoma has not been previously reported.

Acute Disease↗
PubMed1987

Multimodality treatment in anaplastic giant cell thyroid carcinoma.

Anaplastic giant cell thyroid carcinoma is highly malignant. Surgery, chemotherapy, or radiotherapy used separately have not been effective. Combinations of the three modalities have been used at Radiumhemmet since the middle of the 1970s. Nine patients received three-drug chemotherapy and radiotherapy. One patient was alive after 12 years; eight died. Twenty-five patients were given a similar regimen (with two fractions of radiotherapy per day), aiming at surgery. Twelve patients could undergo surgery. Two were alive 11 and 3.5 years after diagnosis. One patient died free of tumor after 6.5 years. Of the remaining 22 patients, many died of metastatic disease. A combination of preoperative and postoperative radiotherapy, chemotherapy (bleomycin, cyclophosphamide, and 5-fluorouracil) and surgery during the remission has given a 12% (four of 34) survival (greater than 3 years). All survivors had undergone surgery. The patients who died had in many cases achieved local tumor control. Adriamycin (Adria Laboratories, Columbus, OH) once a week replaced BCF due to treatment complications in patients receiving BCF. Of five patients, only one was alive more than 10 months after treatment.

Bleomycin↗
PubMed1988

Patient compliance with aggressive multimodal therapy in locally advanced breast cancer.

This study of compliance was performed to determine whether a medically indigent population with breast carcinoma that has been neglected is an appropriate group for inclusion in an aggressive combined treatment program. After incisional biopsy, 28 locally advanced breast cancer (LABC) patients received two cycles of cytoxan, Adriamycin, 5-Fluorouracil, and tamoxifen (CAFT) followed by a simple mastectomy and level I axillary dissection. After surgery, patients received four additional cycles of CAFT alternating with three cycles of 15 Gy to the chest wall and regional lymphatics. Compliance was defined as overall compliance, the percentage of patients completing the protocol as described; and appointment compliance, the ratio between treatments or appointments attended versus those scheduled. Overall compliance was 75% (21 of 28 patients). The total number of appointments scheduled was 1054 (mean, 37 +/- 2), and the total attended was 965 (mean, 34 +/- 3), giving an appointment compliance rate of 91.7%. Compliance did not vary significantly with age, marital status, nationality, the presence of complications, or delay to diagnosis. Compliance did decrease significantly with time. There was 100% overall compliance at 2 months, 82% at 6 months, and 75% at 1 year. We conclude that although our patients had neglected their disease and were medically indigent, they were highly motivated patients once in therapy. This suggests that complex treatment regimens are feasible as well as effective for the treatment of LABC.

Adult↗
PubMed1988

Six-year results of a multimodality treatment strategy for locally advanced breast cancer.

Between 1976 and 1982, 59 patients with locally advanced breast cancer were treated with preoperative supervoltage radiotherapy, adjuvant preoperative and postoperative hormonochemotherapy, and modified radical mastectomy. Systemic treatment, which was started simultaneously with radiotherapy, consisted of a combination of daily oral tamoxifen and a monthly alternation of Doxorubicin + vincristine and cyclophosphamide + methotrexate + 5-fluorouracil (CMF). One of each cycle was given preoperatively at half dosage and five of each were repeated postoperatively at full dosage. All patients became operable. Results of pathologic examination of the operative specimen, available in 51 patients, showed complete disappearance of tumor tissue in breast areas in eight patients, of which three still had positive axillary nodes. After a median follow-up time of 6 years locoregional failure was observed in 12 patients (20%) but in only three (5%) did it occur before distant failure. The actuarial median survival of the entire patient population is close to 4 years. Seven patients are alive without recurrence at greater than 9 years. This aggressive multidisciplinary treatment approach is associated with a projected 30% long-term survival (10 years), excellent local control, but substantial toxicity.

Adult↗
PubMed1989

Effect of perioperative transfusions on survival in osteosarcoma treated by multimodal therapy.

We report on a retrospective study of 155 patients amputated for nonmetastatic osteosarcoma of the long bones. Among the various prognostic variables considered, a significant correlation was found only between survival and transfusions. In this report, the authors consider some hypotheses reported by others for tumors of a different nature and site and conclude that perioperative transfusion may induce depression in the immune response, which is the cause of a shorter survival in the patients reviewed.

Adolescent↗
PubMed1990

The role of surgery in the multimodal treatment of primary gastric non-Hodgkin's lymphomas. A report of 76 cases and review of the literature.

Seventy-six patients with primary gastric non-Hodgkin's lymphomas (PGL) were diagnosed, and 75 were treated between 1975 and 1985. According to the Working Formulation 22 patients had low-grade malignant histologic subtypes, 27 intermediate-grade, and 27 high-grade. Twenty-four cases were diagnosed by endoscopic biopsies, 52 through laparotomy biopsies. Forty-five underwent subtotal or total gastric resection; seven were considered unresectable at laparotomy; 23 did not undergo surgery because of the high operative risk, mainly due to advanced age and coexisting diseases; and one died of myocardial infarction a few days after admission, before starting therapy. All patients who did not undergo laparotomy were staged with bipedal lymphangiography or abdominal ultrasonography and/or computed tomography. Stage, evaluated according to the criteria of Musshoff, was I or II1 in 16 cases, II2 in five, and IV in the remaining 55. Treatment modalities included surgery (S), chemotherapy (CT), radiotherapy (RT), and combinations thereof in the following proportions: only S in ten cases, S + CT in 32 cases, S + RT in one case, S + CT + RT in two cases, CT only in 25 cases, CT + RT in five cases. No substantial differences in response to therapy and in survival were found in relation to the different treatments. Ten-year survival was 43% in Stage I or II and 20% in Stage IV. Of the 45 resected patients, five postoperative deaths were recorded (11%). No bleeding or perforations were observed in the 30 unresected patients, and survival of such cases compared with that of the resected ones. These findings, together with data from the literature, suggest that some of the advantages claimed for surgery in PGL (debulking and abatement of the risk of perforation or hemorrhage during CT or RT) have been overestimated in relation to the intrinsic surgical risk and to the possibility of anticancer therapy. Gastric resection may still be unavoidable as a diagnostic procedure in a minority of cases and may represent the primary therapeutic procedure in clinically assessed early-stage and low-risk patients, but it cannot be considered mandatory whenever possible merely for debulking purposes or to obviate possible perforation or hemorrhage. The CT and/or RT can be effective in unresected and even bulky cases, providing minimal risk of severe hemorrhage or perforation.

Adolescent↗