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Thyroid lymphoma. The case for combined modality therapy.

BACKGROUND: Radiation therapy with or without surgery is generally considered standard treatment for lymphoma of the thyroid. Because of the small number of cases, the role of chemotherapy or combined modality treatment is difficult to determine. METHODS: The published literature was analyzed, supplemented by a series from Yale, for the incidence of local and distant relapse after radiation therapy, chemotherapy, or combined modality treatment for Stage I-II thyroid lymphoma. Patients with advanced disease or in whom radiation was probably inadequate were excluded. Only patients receiving an anthracyline-based regimen were considered in the group with chemotherapy. Patients receiving single agents or non-anthracycline-based regimens were excluded from analysis or, if they also received radiation, were included in the group that received radiation only. RESULTS: Including a series from Yale, a total of 211 patients with Stage IE and IIE thyroid lymphoma were identified. Distant and overall relapse rate were significantly lower in the group that received combined modality treatment. Local relapse was also less, but the difference was not statistically significant. In a small number of patients with disease confined to the neck, the results with radiation were similar to combined modality treatment if the mediastinum was included in the treatment port. CONCLUSION: Although mucosa-associated lymphoma tissue lymphomas are thought to have a low distant recurrence rate and are therefore often treated with local therapy alone, a review of the published literature suggests that 30% of thyroid lymphomas with clinically localized disease will have a distant relapse. The addition of chemotherapy to radiation significantly lowered distant and overall recurrence.

Aged↗

Potential role for epidermal growth factor receptor inhibitors in combined-modality therapy for non-small-cell lung cancer.

There has been a surge of interest in the translation of discoveries in molecular biology into clinically relevant therapies in the field of hematology/oncology. The epidermal growth factor receptor (EGFR) has been a molecular target of significant interest and investigation, and preclinical and clinical studies support a role for targeted therapy in a variety of cancers, including non-small-cell lung cancer (NSCLC) via compounds that specifically inhibit EGFR. ZD1839, IMC-C225, and OSI-774 are the most clinically developed of these compounds. Interestingly, preclinical studies have demonstrated that EGFR inhibitors may have radiation-sensitizing properties, as well as increased cytotoxic activity in combination with chemotherapeutic agents, suggesting a potential role for EGFR inhibitors as an adjunct to the current combined-modality approach for therapy of Stage III NSCLC. Therefore, clinical trials have been proposed and initiated to address the issue of determining the impact of the addition of EGFR inhibitors to the standard combined-modality regimen (chemotherapy/radiation therapy +/- surgery) for Stage III NSCLC. This article reviews preclinical and clinical data supporting the role for EGFR inhibitors alone or in combination with chemotherapy/radiation therapy for locally advanced NSCLC. Also, it will provide an overview of ongoing and proposed clinical studies investigating the potential role for EGFR inhibitors in Stage III NSCLC.

Antibodies, Monoclonal↗

Combined modality therapy of rectal cancer: decreased acute toxicity with the preoperative approach.

PURPOSE: We compared the combined radiation therapy (RT) plus chemotherapy segments of two separate parallel phase I trials to determine if combined pelvic RT, fluorouracil (5-FU), and high-dose leucovorin (LV) had less acute toxicity when delivered preoperatively versus postoperatively in patients with rectal cancer. PATIENTS AND METHODS: Patients with unresectable disease received preoperative RT plus LV and 5-FU followed by surgery and postoperative LV and 5-FU. Patients with resectable disease received identical doses, techniques, and schedules of RT and LV and 5-FU except all therapy was delivered postoperatively. On day 1, patients received LV and 5-FU times one cycle. RT began on day 8. A second cycle of LV and 5-FU was given concurrently with the fourth week of RT. RESULTS: Although more patients (75% v 32%; P = .02) received the higher dose level of 5-FU (250 mg/m2), significantly fewer experienced acute grade 3 to 4 toxicity with preoperative versus postoperative therapy (13% v 48%; P = .045). There was no grade 3 to 4 myelosuppression in either group. The two grade 3 toxicities in the preoperative group were gastrointestinal. The grade 3 toxicities in the postoperative group included seven gastrointestinal and two genitourinary; four patients had a grade 4 toxicity. CONCLUSION: Given the high incidence of grade 3 to 4 toxicity also reported in the postoperative combined modality adjuvant randomized trials, future adjuvant trials should explore the preoperative approach.

Adult↗

Combined modality therapy of gynecologic cancer.

In the treatment of gynecologic malignancies, various combinations of surgery, drugs, and radiation therapy are used with increasing frequency. An examination is made of data dealing with combined modalities in the treatment of tumors of the cervix, endometrium, and ovary. Although the efficacy of such treatments has not been established, they are increasingly popular. Newer studies now being conducted, together with newer drugs employed in combination with radiation therapy and surgery, can result in the benefits which to date have not been realized.

Adenocarcinoma↗

[10 years' results of combined modality therapy of cervix cancer].

The study was concerned with 5 and 10-year results of combination treatment (surgery + radiation) of 304 cases of cervical cancer. Recurrence and metastases developed in 32 patients (10.5%). The 5-year survival rate for cases with stage I tumor was 95.1% and stage II--90.5%. At 10 years, the said rates were 95.1 and 84.7%, respectively. Minimal effective dose was found to be 1,330 reu.

Adult↗

Biology of esophageal cancer and the role of combined modality therapy.

1. The biology of esophageal cancer involves multifactorial environmental and genetic events. 2. The understanding of the clinical significance of molecular markers is rapidly evolving. 3. Combined-modality approaches should still include surgery in good performance status (ECOG scale < or = 2) patients. 4. Neoadjuvant chemoradiation is probably better than surgical resection alone for patients with potentially curable disease, but only validation of this approach by CALGB-9781 can justify this as a new "proven" standard-of-care in the United States. 5. A pathologic complete response to neoadjuvant therapy is the strongest predictor of long-term survival. 6. 5-FU, by either short course or protracted continuous infusion, comprises the backbone of combination chemotherapy in combined-modality design. 7. Radiation therapy should be given at standard 1.8 to 2 Gy/fraction without a scheduled break. 8. Only by enrolling sufficient numbers of patients in prospective clinical trials will clinicians be able to further define the optimal sequencing and actual necessity of each individual component of combined-modality therapy.

Adenocarcinoma↗

Combined modality therapy of gemcitabine and irradiation on human glioma spheroids derived from cell lines and biopsy tissue.

Multicellular tumor spheroids have been used to examine aspects of combined modality treatment since they often recreate the in vivo tumor environment much more closely than other models. The radioenhancement by gemcitabine (dFdC) on human glioma spheroids derived from cell lines (CLS) and biopsy tissue, grown as organotypic multicellular spheroids (OMS), was studied. CLS of GaMg and U87 and OMS of four glioblastoma patients were used. Radiochemosensitvity was determined using migration and proliferation assays on CLS. In OMS, histology and immunohistochemical studies of MIB-1, p53, and p21 expression were examined 24 and 48 h following treatment. Cell death (ethidium homodimer) was studied using a fluorescence cell viability assay. In CLS, combination treatment led to migration inhibition in GaMg and U87 of 85% and 62% (dFdC 46% and 52%, RT 21% and 43%) and proliferation inhibition of 83% and 85%, respectively. Following dFdC + RT in OMS (% of cases), apoptosis and p21 expression increased (50%), p53 expression increased (75%) and cell proliferation decreased (75%). Only minor morphological damage was observed. Confocal laser scanning microscopy identified an increased dead cell core after dFdC + RT (50%). In conclusion, dFdC can lead to an additively radioenhancement in CLS and individual OMS.

Antimetabolites, Antineoplastic↗

Three-year results of combined modality therapy in locally advanced, resectable squamous cell carcinoma of the head and neck.

Results of a combined therapy, consisting of preoperative chemotherapy, radical resection and postoperative irradiation, of 51 locally advanced, previously untreated, resectable squamous cancers of the head and neck are reported. The overall response rate to chemotherapy was 58.5% (with 33% complete remissions) and higher in carcinomas of the oral cavity and hypopharynx than of the supraglottis and oropharynx. Three year survival was 53% for the entire group, 75% for hypopharyngeal, 58% for oral, 50% for supraglottic and 32% for oropharyngeal lesions, in responders to chemotherapy statistically significant higher than in non responders and only 18% in the fifteen patients who developed recurrences.

Adult↗

Risk-adapted, combined-modality therapy with VAMP/COP and response-based, involved-field radiation for unfavorable pediatric Hodgkin's disease.

PURPOSE: To evaluate the efficacy of vinblastine, doxorubicin, methotrexate, and prednisone (VAMP) and cyclophosphamide, vincristine, and procarbazine (COP) chemotherapy and response-based, involved-field radiation, a combined-modality regimen that limits doses of alkylating agents, anthracyclines, and radiation, in children with advanced and unfavorable Hodgkin's disease. PATIENTS AND METHODS: From 1993 to 2000, 159 children and adolescents with unfavorable Hodgkin's disease received three alternating cycles (total of six cycles) of VAMP/COP chemotherapy followed by response-based, involved-field radiation therapy: 15 Gy was administered to patients achieving a complete response, and 25.5 Gy was administered to those achieving a partial response after the first two cycles of chemotherapy and to all sites of bulky lymphadenopathy. Unfavorable disease was defined as clinical stage I and II with bulky peripheral nodal disease greater than 6 cm, initial bulky mediastinal mass 33% or more of the intrathoracic diameter, and/or "B" symptoms and all stage III and IV. RESULTS: Study enrollment was closed after an interim analysis estimated a 5-year event-free survival (EFS) rate below a predefined level. Disease presentation was localized (stage I/II) in 77 patients (48.4%) and advanced (stage III/IV) in 82 patients (51.6%). At a median follow-up of 5.8 years (range, 1.3 to 10.0 years), 38 patients had events, including relapse/progression (n = 35), second malignancy (n = 2), and accidental death (n = 1); nine relapses (25.7%) occurred greater than 4 years from diagnosis. Five-year survival and EFS estimates are 92.7% +/- 2.5% and 75.6% +/- 4.1%, respectively. CONCLUSION: Risk-adapted combined-modality therapy with VAMP/COP and response-based, involved-field radiation therapy results in an unsatisfactory outcome for pediatric patients with unfavorable presentations of Hodgkin's disease.

Adolescent↗