Intensity-modulated radiation therapy reduces the dose to normal tissue in T2N0M0 squamous cell carcinoma of the glottic larynx

The purpose of this paper was to compare intensity-modulated radiation therapy (IMRT) and conventional planning for T2N0M0 squamous cell carcinoma (SQCC) of the glottic larynx. Three patients with T2N0M0 SQCC are presented who were treated with IMRT. Conventional plans were also generated for comparison purposes. Isodose distributions and dose-volume histograms (DVHs) were generated for all the plans to evaluate the fitness of the plan as well as the differential benefit of IMRT vs. conventional treatment. The isodose distributions that were obtained by the IMRT plan are much more conformal to the planning target volume (PTV) and clearly show that less healthy tissue is subjected to a high-dose level, thus reducing toxicity. IMRT offers better comformality without compromising the PTV coverage and delivers less dose to normal tissues as compared to conventional radiation therapy in T2N0M0 SQCC of the glottic larynx. With an increase in conformality, it is expected to have an increase in the therapeutic ratio.     

Combination chemotherapy with mitomycin C, adriamycin, and cyclophosphamide (MAC) in stage III and IV ovarian cancer

Twenty-nine patients with stages III and IV epithelial carcinomas of the ovary were treated with a combination of mitomycin-C, adriamycin, and cyclophosphamide (MAC). A 62% response rate (CR + PR) was observed in previously untreated patients with a median survival of responding patients of 100+ weeks, compared to 29 weeks for nonresponding patients (p less than 0.001). Toxicity was acceptable with moderate to severe but manageable myelosuppression. Prospective, randomized trials comparing this drug combination to others with demonstrated efficacy are indicated.     

Evidence for clonal disease by magnetic resonance imaging in patients with hypoplastic marrow disorders

Some patients with hypoplastic marrow disorders, including aplastic anemia (AA), are at risk for clonal evolution to myelodysplastic syndromes (MDS) and leukemia. Magnetic resonance imaging (MRI) of marrow of the spine, pelvis, and femurs was performed in 24 patients with hypoplastic marrow disorders. In 12 patients (three AA, nine MDS) MRI was compatible with the clinical and biopsy diagnoses and served to define the spectrum of marrow patterns in these disorders. In eight patients with hypocellular marrow biopsies and a clinical diagnosis of AA, MRI showed an unexpected inhomogeneous or diffuse cellular pattern. Concurrent or subsequent marrow or cytogenetic studies have led to diagnoses of hypoplastic MDS in seven of these patients. In four patients with prolonged hypoplasia after bone marrow transplantation for lymphoma, a speckled pattern superimposed on a fatty background appeared in serial MRI studies. One case evolved to AML, two developed megaloblastic foci, and one remains hypoplastic at 19 months. This study suggests that MRI is able to detect early clonal disease in patients with AA, and can distinguish AA from hypoplastic MDS.     

Results of Treatment in Locally Advanced Carcinoma of the Endometrium

The impact of treatment on survival was analyzed in 106 patients with carcinoma of the endometrium stage II (n=61) and stage III (n=45). There was no significant difference in survival in patients with stage II who were treated with radiation theraphy alone or with combination of surgery and radiation therapy. Their five-year actuarial survival was 74.5% and 71.3% respectively (p=≥0.05). However, combined treatment was associated with significantly superior survival in patients with stage III disease where the survival was 57.3% versus 17.5% in patients who received irradiation alone (p=0.01). Diagnosis of stage III disease based upon clinical (CS III) or pathological (PS III) findings was responsible for this difference in survival. Patients with CS III whose tumor could not be resected because of its extent carried poorer prognosis. Patients with stage II had excellent tumor control in pelvis as compared to patients with stage III. Treatment-related complications were minimal. Overall survival of patients with stage 111 was poor (33.8%) due to a high rate of pelvic and/or extrapelvic recurrences.     

Stage III carcinoma of the endometrium. Results of treatment

The impact of treatment on survival was analysed in 45 patients with stage III carcinoma of the endometrium. Our results indicate that patients treated with a combination of surgery and radiation therapy did significantly better than those treated with radiation alone. The five-years survival was 57.3% and 17.5%, respectively (p = 0.01). Patients with clinical stage III (CS III) whose tumor could not be resected surgically did poorly than patients with pathological stage III (PS III). This difference, however, was not statistically significant (p = greater than 0.05). Treatment related complications were minimal. Overall survival of patients of 33.8% was directly attributable to increased pelvic and/or extra pelvic recurrences.     

Mitomycin-C alone and in combination with infused 5-fluorouracil in the treatment of disseminated gastrointestinal carcinomas

One hundred and thirty-two previously untreated patients with metastatic adenocarcinoma of the gastrointestinal (GI) tract were randomized to receive either a 120-hr infusion of 5-fluorouracil (5FU) with mitomycin-C or mitomycin-C alone. Superiority of the combination treatment was demonstrated with remissions in 30 out of 82 (37%) patients versus 9 out of 50 (18%) with the single drug treatment (P = 0.02). The median survival with 5FU—mitomycin-C was 29 weeks, as opposed to 20 weeks with mitomycin-C alone (P = 0.03). The combination produced significantly more severe myelotoxicity than the single drug, and jaundiced patients experienced more myelosuppression than non-jaundiced patients with both treatments.     

Extrachromosomal gene amplification in acute myeloid leukemia; Characterization by metaphase analysis,comparative genomic hybridization,and semi-quantitative PCR

A case of acute myeloid leukemia (M-3) with complex karyotypic aberrations and double minute (dmin) chromosomes is presented. The patient had no history of prior exposure to mutagenic or carcinogenic agents or of other malignancies. She died from CNS involvement six weeks after the initial diagnosis. We used comparative genomic hybridization to identify the amplified sequences presumed to represent the dmin of the leukemic cells; the tumor/normal ratios indicated increased signal intensity at 8q24. This localization prompted investigation by semi-quantitative PCR that revealed amplification of the MYC oncogene. The extent of chromosome aberrations and the oncogene amplification, both linked with poor prognosis, may relate to the rapid course of this patient's disease. © 1993 Wiley-Liss, Inc.     

High dose chemotherapy and peripheral blood stem cell transplantation for high risk primary breast cancer: a single center experience in Thailand

Twenty patients with high risk primary breast cancer underwent a high dose chemotherapy program at Ramathibodi Hospital, Bangkok. Eligible patients included 21 women who had a histological diagnosis of breast cancer with more than 10 axillary lymph nodes involved. The patients first underwent modified radical mastectomy, followed by conventional doxorubicin containing adjuvant chemotherapy, before entering the treatment program. Peripheral blood stem cells were mobilized with cyclophosphamide and G-CSF and were harvested by leukapheresis. High dose chemotherapy consisted of cyclophosphamide 5,625 mg/m2, cisplatinum 165 mg/m2 and carmustine (BCNU) 600 mg/m2 were subsequently given, followed by infusion of the harvested peripheral blood stem cells. The median duration of cytopenia after transplantation was 8 days (range 7-12). The median expense for the transplantation, in addition to the cost of mastectomy and conventional chemotherapy, was 224,396 Baht (approximately US $5,350). Three out of the first four patients developed interstitial pneumonitis within three months after transplantation. There was one fatal case which was the only regimen related mortality. BCNU was then reduced to 450 mg/m2 and lung complications were markedly reduced afterwards. The median follow up time was 37 months with a median disease free survival of 38 months and overall survival of four years at 84%.     

Liver Graft-Versus-Host Disease is associated with poor survival among allogeneic hematopoietic stem cell transplant recipients

Liver Graft-versus-host disease (GVHD) is common in patients with post-transplant liver dysfunction following allogeneic hematopoietic stem cell transplantation (AHSCT). Oftentimes, the diagnosis is made clinically, and liver biopsy is deferred. Our objective was to evaluate the risk factors and clinical outcomes of liver GVHD among patients who developed post-transplant liver dysfunction. Additionally, we evaluated the feasibility of liver biopsy in this population. We compared outcomes between liver GVHD and a “non-liver GVHD” group, which consisted of other etiologies of post-transplant liver dysfunction. Between January 2003 and December 2010, 249 patients developed post-transplant liver dysfunction following AHSCT: 124 patients developed liver GVHD and 125 were in the “non-liver GVHD” group. The incidence of acute and chronic liver GVHD at one year was 15.7% and 31.0%, respectively. The competing risk analysis revealed full intensity conditioning regimen (Hazard ratio [HR], 1.76; P = .008) and related donor (HR, 1.68; P = .004) as independent risk factors for liver GVHD. The time-varying covariate Cox regression analysis with competing risk event, demonstrated that liver GVHD was independently associated with higher non-relapse mortality, and adverse relapse-free and overall survival. A total of 112 liver biopsies were performed in 100 patients. No major complications were observed. Liver biopsy confirmed prebiopsy hypotheses in 49% of cases, and led to treatment modification in 49% of patients. Our study shows that liver GVHD is associated with adverse survival. Liver biopsy is safe and often helps directing care in this setting.