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Malignant germ cell tumor of the mediastinum: a multimodality therapeutic approach.

Twenty-five patients with a malignant germ cell tumor of the mediastinum were treated at the National Cancer Center Hospital, Tokyo. Three patients had pure seminomas while 22 had a nonseminomatous histology. The treatment modalities consisted of surgery alone in 7 patients, surgery with chemotherapy and/or radiation in 14, and chemotherapy and/or radiation without surgery in 4. Cisplatin-based chemotherapy was administered in nine patients, one of whom successfully underwent high-dose chemotherapy with autologous bone marrow transplantation after resection of the tumor. A complete response was achieved in only five patients. The overall survival rate at 5 years was 33.5% and the median survival time was 51 weeks. Eight patients (32%), all of whom underwent surgery either with or without chemotherapy and/or radiation, were free of disease with a mean follow-up period of 439 weeks (72-1,120 weeks). The median survival times for 14 patients undergoing combined modality treatment, 7 patients undergoing surgery alone, and 4 patients undergoing chemotherapy and/or radiation were 83, 16, and 18 weeks, respectively.

Adolescent↗

Influence of multimodality therapy on the cellular immunity of patients with esophageal cancer.

BACKGROUND: Cancer patients have often been reported to have impaired immune function, and the effect of treatment modalities, such as surgery, irradiation, and chemotherapy, in depressing patients' immunity has also been reported. In this investigation, the effect of treatment on the cellular immunity of esophageal cancer patients was evaluated. METHODS: Immunological parameters, such as natural killer (NK) activity and lymphocyte subsets in peripheral blood, were measured in 32 esophageal cancer patients on 5 occasions (on the day of admission, 2 days before surgery, and 1 week, 1 month, and 2 months after surgery). RESULTS: NK activity was greatly impaired shortly after the operation, and the percentages of lymphocytes as a whole, and CD8+, CD16+, and CD57+ lymphocytes were significantly decreased, on the other hand, a postoperative increase in the CD4+/CD8+ ratio was observed. No significant depression of immune function by postoperative irradiation was observed. CONCLUSIONS: The results of this study suggest that cellular immunity, especially cytotoxicity, shortly after esophagectomy may be greatly impaired by the surgical stress of esophagectomy and an added effect of chemotherapy.

Aged↗

Multimodality approach to staging renal cell carcinoma.

Renal imaging has dramatically improved since the introduction of ultrasound (US), computed tomography (CT), and most recently magnetic resonance (MR) imaging. US and MR imaging are ideal for patients with compromised renal function preventing administration of iodinated contrast material or those who have experienced reactions to contrast. Staging errors occur due to limitations in assessing microscopic tumor invasion of the renal capsule and perinephric fat, detecting metastatic deposits in normal sized lymph nodes and differentiating inflammatory hyperplastic lymph nodes from neoplastic ones. These limitations are shared by US, CT, and MR imaging. Vascular invasion by tumor can be evaluated by all imaging modalities including venography. The advantages and limitations of each examination will be presented.

Angiography↗

Multimodal imaging in evaluation of two cases of adenocarcinoma of the renal pelvis.

Primary adenocarcinoma arising in the renal pelvis is a rare entity. Two cases are presented in which computed tomography (CT), ultrasound, and antegrade pyelography were performed in addition to conventional urographic methods. One patient's multifocal tumor involving several calyces was best demonstrated by ultrasound; the other patient's centrally placed pelvic mass was seen by CT. Adenocarcinomas are etiologically linked to repeated infection. Although it has been stated in previous reviews that the diagnosis of malignancy is seldom made preoperatively in these patients, the use of CT, ultrasound, and antegrade pyelography allowed the diagnosis to be made prospectively in both cases.

Adenocarcinoma↗

Durable remission of locally advanced breast cancer with multimodality management.

We treated 20 women with locally advanced breast cancer between January 1991 and September 1996. The treatment regimen included 4 cycles of intensive doxorubicin (30 mg/m2/d on 3 consecutive days every 2 weeks with G-CSF support), followed by appropriate surgery, followed by high dose therapy with cyclophosphamide, carboplatin and thiotepa (STAMP V, CTCb). Of the 20 patients, seven presented with inflammatory breast cancer, three with Stage IIIB, seven with stage IIIA, one with multifocal Stage IIB and two with Stage IV M1 (ipsilateral supraclavicular lymph node involvement) (including one who had an inflammatory primary) disease. Six patients had not undergone mastectomy at the time of entering the protocol. These six received the doxorubicin in a neoadjuvant fashion and were thus evaluable for tumor response. The remaining 14 received doxorubicin as adjuvant therapy prior to intensification and transplantation. All patients underwent local-regional radiation therapy and were placed on oral tamoxifen. Doxorubicin was well tolerated in this schedule with all but three patients receiving all their cycles on schedule. Both BM and PBPC were easily collected after this regimen and, when reinfused, resulted in the prompt recovery of granulocytes (median 11 days to 500 absolute granulocyte count) and platelets (median 13 days to 20,000 platelets). The six patients who received doxorubicin prior to mastectomy all had major clinical responses, but were found to have microscopic focii of breast cancer in the mastectomy specimens. The overall treatment was well tolerated with the exception of one treatment-related death (5%). The overall and relapse free survival are 70% and 58% respectively with a median follow-up of 40 months (range 12-74 months). When the Stage IV patients are censored, the relapse-free survival rate is 69%. In the bone marrow transplant phase of treatment, the major non-hematologic toxicities were stomatitis (70%) and anorexia requiring parental nutrition (75%).

Adult↗

[Use of G-CSF (Neupogen) in multimodal treatment in radiotherapy].

BACKGROUND: Therapy-induced leukopenias with corresponding consequences repeatedly occur in radiotherapy using combined modalities treatment. In radiotherapy, where G-CSF (granulocyte-colony-stimulating-factor) is not licensed, G-CSF has been used successfully under individual circumstances. These results were confirmed in several studies with small patient groups. The aim of this study was to check former results in a larger patient group, to verify postulated side effects and specially to define a cost-effective schedule in the treatment with G-CSF (Neupogen). PATIENTS AND METHODS: In this surveillance trial 50, partially previously treated patients with different malignant tumors were treated with G-CSF. According to the probability of a leucocytosis lower than 1000/mm3, G-CSF (Neuropogen) was already given at leukocyte values lower than 2500/mm3 (500/mm3 bis 2450/mm3). It administered subcutaneously every other day, based on body weight until reaching normal leucocyte levels. RESULTS: In 92% of the patients the increase of leucocytes occurred in the first 24 hours. On average G-CSF was given 4.9 times per patient. Patients without prior therapies or less complex therapies needed less G-CSF applications (3.5 to 5.8 applications). Due to individually varying leucocyte courses the G-CSF therapy was started with leucocyte values between 500/mm3 and 2450/mm3. Patients who were treated with up to 3 G-CSF applications had higher leucocyte levels than those with 4 or more applications (1620/mm3 to 1250/mm3). Leucopenia related infections, therapy interruptions or break-offs did not occur. Besides light "flu like" symptoms in 14% of the patients, no side effects were observed. CONCLUSIONS: When a decrease of leucocyte values lower than 1000/mm3 is expected, the most cost-effective treatment is given when starting the interventional G-CSF administration already at leucocyte values around 1600/mm3. Leucopenias can be treated effectively, with little side effects and in a cost-effective way when G-CSF is given on time.

Adult↗

Three-dimensional display of cortical anatomy and vasculature: magnetic resonance angiography versus multimodality integration.

We present two methods for acquiring and viewing integrated three-dimensional (3D) images of cerebral vasculature and cortical anatomy. The aim of each technique is to provide the neurosurgeon or radiologist with a 3D image containing information which cannot ordinarily be obtained from a single imaging modality. The first approach employs recent developments in MR which is now capable of imaging flowing blood as well as static tissue. Here, true 3D data are acquired and displayed using volume or surface rendering techniques. The second approach is based on the integration of x-ray projection angiograms and tomographic image data, allowing a composite image of anatomy and vasculature to be viewed in 3D. This is accomplished by superimposing an angiographic stereo-pair onto volume rendered images of either CT or MR data created with matched viewing geometries. The two approaches are outlined and compared. Results are presented for each technique and potential clinical applications discussed.

Brain↗

Radiation therapy in the multimodal treatment approach of pituitary adenoma.

BACKGROUND: Pituitary tumors are relatively uncommon, comprising 10-12% of all intracranial tumors. The treatment consisting of surgery, radiotherapy and drug therapy or a combination of these modalities is aimed at the control of tumor cell proliferation and--in endocrine active tumors--the reduction of hormone secretion. However, the slow proliferation characteristics of pituitary tumors necessitate long-term studies for the evaluation of the treatment results. In the last decade there has been continuous improvement in surgical procedures, radiotherapy techniques and drug generation. In this paper, literature will be reviewed to assess the role of modern radiotherapy and radiosurgery in the management of pituitary adenomas. MATERIAL AND METHODS: Nowadays, magnetic resonance imaging for the definition of the target volume and a real three-dimensional (3-D) treatment planning with field conformation and the possibility for non-coplanar irradiation has to be recommended. Most groups irradiate these benign tumors with single doses of 1.8-2.0 Gy up to a total dose of 45 Gy or 50.4 Gy in extensive parasellar adenomas. Adenomas are mostly small, well circumscribed lesions, and have, therefore, attracted the use of stereotactically guided high-precision irradiation techniques which allow extreme focussing and provide steep dose gradients with selective treatment of the target and optimal protection of the surrounding brain tissue. RESULTS: Radiation therapy controls tumor growth in 80-98% of patients with non-secreting adenomas and 67-89% for endocrine active tumors. Reviewing the recent literature including endocrine active and non-secreting adenomas, irradiated postoperatively or in case of recurrence the 5-, 10- and 15-year local control rates amount 92%, 89% and 79%. In cases of microprolactinoma primary therapy consists of dopamine agonists. Irradiation should be preferred in patients with macroprolactinomas, when drug therapy and/or surgery failed or for patients medically unsuitable for surgery. Reduction and control of prolactin secretion can be achieved in 44-70% of patients. After radiotherapy in acromegaly patients somatomedin-C and growth hormone concentrations decrease to normal levels in 70-90%, with a decrease rate of 10-30% per year. Hypercortisolism is controlled in 50-83% of adults and 80% of children with Cushing's disease, generally in less than 9 months. Hypopituitarism is the most common side effect of pituitary irradiation with an incidence of 13-56%. Long-term overall risk for brain necrosis in a total of 1,388 analyzed patients was estimated to be 0.2%. Other side effects are rare too, and do also depend on the damage produced by tumor itself or preceding surgery. They include deterioration of vision in 1.7% of all cases, vascular changes in 6.3%, neuropsychological disorders such as dementia in 0.7% and secondary malignancies in 0.8%, if single doses of 2.0 Gy and total doses of 50 Gy are not exceeded. CONCLUSION: Conventional radiation therapy of pituitary adenoma is highly effective. It is recommended after subtotal resection of primary tumors such as macroadenomas, after gross total resection from endocrine active adenomas with postsurgical hormone secretion and for recurrent tumors. Radiosurgery seems to be a possible treatment alternative in experienced centers, and only in patients with adenomas smaller than 25-30 mm with a minimum distance of 2-3 mm to the chiasm.

Acromegaly↗

Multimodality cranial image fusion using external markers applied via a vacuum mouthpiece and a case report.

PURPOSE: To present a simple and precise method of combining functional information of cranial SPECT and PET images with CT and MRI, in any combination. MATERIAL AND METHODS: Imaging is performed with a hockey mask-like reference frame with image modality-specific markers in precisely defined positions. This frame is reproducibly connected to the VBH vacuum mouthpiece, granting objectively identical repositioning of the frame with respect to the cranium. Using these markers, the desired 3-D imaging modalities can then be manually or automatically registered. This information can be used for diagnosis, treatment planning, and evaluation of follow-up, while the same vacuum mouthpiece allows precisely reproducible stereotactic head fixation during radiotherapy. RESULTS: 244 CT and MR data sets of 49 patients were registered to a root square mean error (RSME) of 0.9 mm (mean). 64 SPECT-CT fusions on 18 of these patients gave an RMSE of 1.4 mm, and 40 PET-CT data sets of eight patients were registered to 1.3 mm. An example of the method is given by means of a case report of a 52-year-old patient with bilateral optic nerve meningioma. CONCLUSION: This technique is a simple, objective and accurate registration tool to combine diagnosis, treatment planning, treatment, and follow-up, all via an individualized vacuum mouthpiece. Especially for low-resolution PET and even more so for some very diffuse SPECT data sets, activity can now be accurately correlated to anatomic structures.

Equipment Design↗

Multimodality diagnostics and megatherapy in poor prognosis Ewing's tumor patients. A single-center report.

BACKGROUND: The prognosis of Ewing's tumor patients has been improved gradually through cooperative therapy studies, so that meanwhile 55 to 65% of the patients survive relapse-free in the long term. Patients with multifocal primary, early or multiply-relapsed Ewing's tumors have a dismal prognosis. Megatherapy with subsequent stem cell transplantation seems to improve outcome in this patient cohort. Feasibility of this intense megatherapy regimen is crucially dependent on collaboration and multidisciplinary coordination of radiologists, radiotherapists, surgeons and oncologists. PATIENTS AND METHODS: Since 1988, 25 patients were treated with megatherapy consisting of melphalan, etoposide and total-body irradiation followed by stem cell transplantation. All patients received 6 courses of an induction therapy. Before the fourth therapy block, tumors that were bulky at initial diagnosis (> 200 ml) were excised, as well as lung metastases which could still be detected after the third chemotherapy block. During the fifth and sixth chemotherapy block, patients received local irradiation on all infiltrated sites. Persisting immunosuppression after high-dose treatment may facilitate the incidence of relapse. To improve proliferation and cytotoxic activity of early regenerating NK-cells, adoptive immunotherapy with systemic IL-2 therapy after megatherapy is part of the treatment protocol. RESULTS: Of 25 patients treated with megatherapy, 10 patients are still alive with a follow-up time of 6 months to 9 years after megatherapy. The time up to engraftment was decreased from 15 +/- 6 days down to 9 +/- 2 days through the use of G-CSF and CD34+ selected stem cells. At the same time, erythrocyte and platelet replacement was shortened. Frequently occurring complications were mucositis and infections. One patient died after developing septicemia and multi-organ failure, another patient developed a myelodysplastic syndrome 4.5 years after megatherapy. However, relapse is still the major cause of death. The influence of IL-2 on event-free survival cannot valued because 21 of 25 patients were treated with adoptive immunotherapy. CONCLUSION: The complex diagnostic and therapeutic strategy renders and EFS of 34% for a patient group with otherwise dismal prognosis. To clarify the efficiency of megatherapy in patients with advanced Ewing's tumors, a standardized treatment strategy is necessary to accumulate a sufficient number of patients for large cooperative studies in this subject.

Adolescent↗

[T4 rectal carcinoma. Surgical and multimodal therapy].

BACKGROUND: In locally advanced rectal cancer with infiltration of neighbouring organs (uT4), resectability and local control are difficult to achieve. Combined preoperative radiochemotherapy may result in increased resectability and reduced local recurrence rates. PATIENTS AND METHODS: Thirty-four patients with biopsy-proven locally advanced rectal cancer were treated by preoperative radiochemotherapy. All tumours had been staged as uT4 lesions by endorectal ultrasound or computed tomography. Radiotherapy was applied in standard blocks, 5 x 1.8 Gy up to 45 Gy. Chemotherapy consisted of two cycles of 5-fluorouracil (300-350 mg/m2/day) and leucovorin (50 mg). In 20 patients, additional thermotherapy was carried out using the Sigma 60 applicator BSD 2000 once a week prior to radiotherapy. Surgery was performed 4-6 weeks after radiochemotherapy. Postoperatively, all patients received four cycles of 5-fluorouracil and leucovorin. RESULTS: Treatment-induced toxicity occurred in 26% of the patients (WHO grade III (n = 6) and IV (n = 3)). The resectability rate was 76% (26/34 patients) (R0 resectability n = 21; 62%). The pathological complete response rate was 6% (n = 2) and the partial response rate was 47% (n = 16). A local failure was observed in six patients after median time of 16 months (range 7-36 months). Patients with R0 resection achieved a 5-year disease-free survival rate of 55% and a survival rate of 71%. The overall 5-year survival rate for all patients with advanced uT4 rectal cancer was 49%. CONCLUSIONS: Our data on preoperative combined treatment in locally advanced T4 rectal cancer revealed encouraging downstaging, local control, and survival rates.

Adult↗

[Multimodal therapy of colon carcinoma].

A large variety of immunological and cytotoxic adjuvant treatment concepts and application routes have been observed to be effective in colon cancer by randomized trials during the past three decades. Presently adjuvant 5-fluorouracil based chemotherapy is favoured for patients with lymph node metastases (UICC stage III), since this treatment was associated with a 5-10% increase in 5-year survival. Uncertainty persists regarding the optimal use of adjuvant treatment, since marked differences in prognosis have been recognized within stage III and because the impact of surgical treatment on long-term survival has not been thoroughly controlled for in past trials. Current and future studies will have to determine precisely which patients will benefit most from adjuvant treatment and which combination of surgical and adjuvant treatment will be most effective.

Chemotherapy, Adjuvant↗

[Soft tissue sarcoma: prognostic factors and multimodal treatment].

Soft-tissue sarcomas are a relatively rare disease accounting for approximately 1% of adult malignancies. Various different histological subtypes exist that behave similarly regarding their biological characteristics and response to treatment. Soft-tissue sarcomas occur in up to 50% of cases in the extremities, followed by visceral/retroperitoneal and trunk tumors. Primary therapy is predicated on surgical resection with an adequate margin of normal tissue. Limb-sparing surgery for extremity lesions is possible in more than 90% of patients. For high-risk patients, identified by tumor grade, size and site, local control is improved with postoperative adjuvant radiation. Local recurrence rates vary, depending on the anatomic site. In the most common extremity lesions, one-third of the patients develop locally recurrent disease with a median disease-free interval of 18 months. For visceral sarcomas recurrence rates are up to 40-50%. Treatment results for extremity local recurrences may approach those for primary disease. Metastases of extremity sarcomas predominantly spread to the lungs where isolated metastases can be resected with 20-30% 3-year survival rates. Patients with unresectable pulmonary metastases or extra-pulmonary metastatic sarcoma have a uniformly poor prognosis and are best treated with systemic chemotherapy. In general, optimal treatment of soft-tissue sarcoma requires individual care tailored to the single patient.

Adolescent↗

[Multimodal treatment strategy for Langerhans cell histiocytosis at head and neck manifestations].

Langerhans cell histiocytosis (LCH) is a rare disorder with different clinical features. An established standardized treatment does not exist.We present a case report of a patient with localized LCH of the temporal bone and discuss the interdisciplinary treatment strategies. We reviewed the international literature and summarized the current knowledge. Beside a wait and see policy in cases without symptomatic disease, surgery, radiotherapy or chemotherapy, and combinations of these options are used as treatment modalities. While surgery or radiotherapy are preferred in localized (symptomatic) lesions, stage-adapted chemotherapeutic regimens are the treatments of choice in disseminated disease. Treatment selection depends on the individual clinical features.

Adolescent↗