Clinico-pathological study of Hodgkin's lymphoma in a cancer center in Taiwan.

The incidence rate of Hodgkin's lymphoma (HL) in Asia is much lower than that of western countries. This study demonstrates the incidence rate and the clinico-pathological features of HL in a cancer center in Taiwan with respect to demographics, histological subtypes and clinical outcomes. We evaluated the clinical, morphological and immunohistochemical features of 42 patients with HL during the period of 1995-2002. Clinico-pathological features and follow-up were scrutinized. There were 21 males and 21 females. The incidence rate of HL in malignant lymphoma in our center was 7%. The median age was 26 years old. There was no apparent bimodal age distribution. The most prevalent histological subtype was nodular sclerosis (69%). Mixed cellularity, lymphocyte rich, lymphocyte depletion, nodular lymphocyte predominance and unclassified was 4.8%, 4.8%, 0%, 7% and 14% respectively. The most common site at presentation was the cervical lymph node (31 cases; 74%). Clinically, 1 (2%) had stage I disease, 23 (55%) stage II, 8 (19%) stage III and 10 (24%) stage IV. Two cases had rare primary bone marrow HL of stage IV. Both cases died within 1 month. Clinical stage (P=0.09) and age (P<0.001) were prognostic parameters determining the overall survival.

Examining prognostic factors and patterns of failure in nasopharyngeal carcinoma following concomitant radiotherapy and chemotherapy: impact on future clinical trials.

PURPOSE: Concomitant chemotherapy and radiotherapy (CCRT), followed by adjuvant chemotherapy, has improved the outcome of nasopharyngeal carcinoma (NPC). However, the prognosis and patterns of failure after this combined-modality treatment are not yet clear. In this report, the prognostic factors and failure patterns we observed with CCRT may shed new light in the design of future trials. METHODS AND PATIENTS: One hundred forty-nine (149) patients with newly diagnosed and histologically proven NPC were prospectively treated with CCRT followed by adjuvant chemotherapy between April 1990 and December 1997. One hundred and thirty-three (89.3%) patients had MRI of head and neck for primary evaluation before treatment. Radiotherapy was delivered either at 2 Gy per fraction per day up to 70 Gy or 1.2 Gy per fraction, 2 fractions per day, up to 74.4 Gy. Chemotherapy consisted of cisplatin and 5-fluorouracil. According to the AJCC 1997 staging system, 32 patients were in Stage II, 53 in Stage III, and 64 in Stage IV (M0). RESULTS: Univariate analysis revealed that WHO (World Health Organization) Type II histology, T4 classification, and parapharyngeal extension were poor prognostic factors for locoregional control. Multivariate analysis revealed that T4 disease was the most important adverse factor that affects locoregional control, the risk ratio being 5.965 (p = 0.02). Univariate analysis for distant metastasis revealed that T4 and N3 classifications, serum LDH level > 410 U/L (normal range, 180-460), parapharyngeal extension, and infiltration of the clivus were significantly associated with poor prognosis. Multivariate analysis, however, revealed that T4 classification and N3 category were the only two factors that predicted distant metastasis; the risk ratios were 3.994 (p = 0.02) and 3.390 (p = 0.01), respectively. Therefore, based on the risk factor analysis, we were able to identify low-, intermediate-, and high-risk patients. Low-risk patients were those without the risk factors mentioned above. They consisted of Stage II patients with T2aN0, T1N1, and T2aN1 categories and of Stage III patients with T1N2 and T2aN2 categories. Their risk of recurrence is low (4%). Intermediate-risk patients were those with at least one univariate risk factor. They are Stage II patients with T2bN0 and T2bN1 categories and Stage III patients with T2bN2 and T3N0-2 categories. The risk of recurrence is modest (18%). High-risk patients have risk factors by multivariate analysis. They are stage T4 or N3 patients. Their risk of recurrence is high (36%). CONCLUSION: Low-risk patients have an excellent outcome. Future trials should focus on reducing treatment-associated toxicities and complications and reevaluate the benefit of sequential adjuvant chemotherapy. The recurrence in treatment of intermediate-risk patients is modest; CCRT and adjuvant chemotherapy may be the best standard for them. Patients with T4 and N3 disease have poorer prognosis. Hyperfractionated radiotherapy may be considered for the T4 patients. Future study in these high-risk patients should also address the problem of distant spread of the disease.

Long-term survival of nasopharyngeal carcinoma following concomitant radiotherapy and chemotherapy.

PURPOSE: The purpose of this study is to demonstrate long-term survival of nasopharyngeal carcinoma treated with concomitant chemotherapy and radiotherapy (CCRT) followed by adjuvant chemotherapy. METHODS AND PATIENTS: One hundred and seven patients with Stage III and IV (American Joint Committee on Cancer, AJCC, 1988) nasopharyngeal carcinoma (NPC) were treated with concomitant chemotherapy and radiotherapy (CCRT) followed by adjuvant chemotherapy between April 1990 and December 1997 in Koo Foundation Sun Yat-Sen Cancer Center, Taipei. The dose of radiation was 70 Gray (Gy) given in 35 fractions, 5 fractions per week. Two courses of chemotherapy, consisting of cisplatin and 5-fluorouracil, were delivered simultaneously with radiotherapy in Weeks 1 and 6 and two additional monthly courses were given after radiotherapy. According to the AJCC 1997 staging system, 32 patients had Stage II disease, 44 had Stage III, and 31 had Stage IV disease. RESULTS: With median follow-up of 44 months, the 5-year overall survival rate in all 107 patients was 84.1%, disease-free survival rate was 74.4%, and locoregional control rate was 89.8%. The 3-year overall survival for Stage II was 100%, for Stage III it was 92.8%, and for Stage IV, 69. 4% (p = 0.0002). The 3-year disease-free survival for Stage II was 96.9%, for Stage III it was 87.7%, and for Stage IV it was 51.9% (p = 0.0001). CONCLUSION: CCRT and adjuvant chemotherapy is effective in Taiwanese patients with advanced NPC. The prognosis of AJCC 1997 Stage II and III disease is excellent, but, for Stage IV (M0), it is relatively poor. Future strategies of therapy should focus on high-risk AJCC 1997 Stage IV (M0) cohort.

Concomitant radiotherapy and chemotherapy for early-stage nasopharyngeal carcinoma.

PURPOSE: Early-stage nasopharyngeal carcinoma (NPC) continues to carry a failure rate of 15% to 30% when treated with radiotherapy alone; the benefit of concomitant radiotherapy and chemotherapy (CCRT) in early-stage NPC is unclear. The purpose of this report is to describe our efforts to improve treatment outcome in early-stage NPC after CCRT. PATIENTS AND METHODS: Of 189 newly diagnosed NPC patients without evidence of distant metastases who were treated in our institution between 1990 and 1997, 44 presented with early-stage (stage I and II) disease according to the American Joint Committee on Cancer (AJCC) 1997 NPC staging system. Twelve of these patients were treated with radiotherapy alone and 32 with CCRT. Each patient's head and neck area was evaluated by magnetic resonance imaging or computed tomography. Radiotherapy was administered at 2 Gy per fraction per day, Monday through Friday, for 35 fractions for a total dose of 70 Gy. Chemotherapy consisting of cis-diamine-dichloroplatinum and fluorouracil was delivered simultaneously with radiotherapy in weeks 1 and 6 and sequentially for two monthly cycles after radiotherapy. RESULTS: Patients who were treated with radiotherapy alone primarily had stage I disease, whereas none of those who were treated with CCRT had stage I disease (11 of 12 patients v none of 32 patients; P =.001). The locoregional control rate at 3 years for the radiotherapy group was 91.7% (median follow-up period, 34 months) and was 100% for the CCRT group (median follow-up period, 44 months) (P =.10). The 3-year disease-free survival rate in the radiotherapy group was 91.7% and was 96.9% in the CCRT group (P =.66). CONCLUSION: Our results reveal excellent prognosis of AJCC 1997 stage II NPC treated with CCRT. Stage II patients with a greater tumor burden treated with CCRT showed an equal disease-free survival, compared with stage I patients treated with radiotherapy alone. A prospective randomized trial is underway to confirm the role of CCRT in stage II NPC.

Assessment of the inhalation technique in outpatients with asthma or chronic obstructive pulmonary disease using a metered-dose inhaler or dry powder device.

Inhaled medication is commonly prescribed for the treatment of asthma and chronic obstructive pulmonary disease (COPD), but is often not properly used by patients. A total of 316 patients suffering from asthma or COPD took part in a study that evaluated how patients utilized their metered-dose inhaler (MDI) or dry powder inhaler, using a standardized inhaler checklist. Two hundred eighty-one patients (88.9%) made at least one mistake in the inhalation technique. The mistakes were classified into skill and nonskill mistakes. Two hundred patients made one or more skill mistakes and 81 patients only made one or more nonskill mistakes. The most common skill error was "not continuing to inhale slowly after activation of the canister" (69.6%). The nonskill item most patients had difficulties with was "exhale before the inhalation" (65.8%). Patients who used an MDI made significantly fewer nonskill mistakes than patients using a dry powder device. Older patients had more difficulty with the correct use of the inhaler than younger patients. There was no difference in errors between men and women. In this patient sample, most patients failed to use their inhaler correctly. Regular instructions and checkups of inhalation technique are the responsibility of the physician and should be a standard and routine procedure.

Prognostic features and treatment outcome in locoregionally advanced nasopharyngeal carcinoma following concurrent chemotherapy and radiotherapy.

PURPOSE: Concurrent chemotherapy and radiotherapy (CCRT) are effective in treatment of locoregionally advanced nasopharyngeal carcinoma (NPC). However, the prognostic factors after CCRT have not been evaluated. We therefore attempt to evaluate factors that influence treatment outcomes following CCRT. METHODS AND MATERIALS: Seventy-four (5 in stage III and 69 in stage IV) patients with locoregionally advanced NPC were treated with CCRT. Radiotherapy was delivered either at 2 Gray (Gy) per fraction per day up to 70 Gy or 1.2 Gy, 2 fractions per day, up to 74.4 Gy. Concurrent chemotherapy consisted of cisplatin and 5-fluorouracil. Cox proportional-hazards model was used to analyze the prognostic factors which included age, gender, pathologic type, T, N, lactate dehydrogenase (LDH), and infiltration of the clivus. RESULTS: The primary tumor control rate at 3 years was 96.7% (95% confidence interval [CI]: 92.5-100), distant metastasis-free survival 81.1% (95% CI: 70.6-91.6), disease-free survival 77.0% (95% CI: 65.3-88.7), and overall survival 79.8% (95% CI: 69.2-90.4) with a median follow-up interval of 29 months (range 15-74 months). Cox proportional-hazards model revealed that infiltration of the clivus and serum level of LDH before treatment were the most two important factors that predict distant metastases. Infiltration of the clivus and the serum LDH level greater than 410 U/L were strongly associated with distant metastasis-free survival (p = 0.0004 and p = 0.0002, respectively). When these two risk factors were considered together, no distant metastasis was observed in 40 patients with both intact clivus and LDH < or = 410 U/L. On the contrary, 13 of the remaining 34 patients with at least one risk factor developed distant metastasis (p = 0.0001). CONCLUSION: Our study demonstrates that CCRT can improve the primary tumor control of 96.7% and disease-free survival of 77.0% at 3-year follow-up. Distant metastasis, however, is the major cause of failure. Infiltration of the clivus by the tumor and LDH greater than 410 U/L are the two independent and useful prognostic factors in patients with locoregionally advanced NPC who were treated with CCRT. Good- and poor-risk patients can be distinguished by virtue of their having both conditions.

Small cell carcinoma of the uterine cervix with large cell neuroendocrine carcinoma component.

A case of cervical small cell carcinoma (SCC) with large cell neuroendocrine carcinoma (LCNC) differentiation is presented. A 35-year-old Taiwanese woman was diagnosed as having stage IIB bulky SCC confirmed by cervical biopsy and underwent induction combination chemoradiotherapy followed by hysterectomy. The pathology of the cervical tumor after the initial treatment showed the residual tumor to be LCNC instead of SCC. Histochemistry, immunohistochemistry, and electron microscopy demonstrated presence of neuroendocrine differentiation on both the biopsy and the surgical specimens. Following surgical resection a course of adjuvant chemotherapy and a local radiation boost were added. Despite complete local control, she developed brain metastasis 8 months later and vertebral spread soon thereafter. The pathology of the brain tumor showed pure SCC. The patient died 19 months after diagnosis and 13 months after completion of treatment. This case suggests that SCC with LCNC component has a similar clinical course as a pure SCC.

Post-remission intensive consolidation with high-dose cytarabine-based chemotherapy and granulocyte colony-stimulatory factor in adults with acute myelogenous leukemia: a preliminary report.

BACKGROUND: Modern induction chemotherapy produce 60% to 80% complete remission in adults with newly diagnosed acute myelogenous leukemia (AML). A major challenge is to eradicate subclinical disease in remission and prevent leukemic relapse. Intensive post-remission chemotherapy was proved of comparable disease-free survival as BMT. METHODS: From February 1992 to to March 1995, twelve patients with AML, aged 15 to 57 y/o, received intensive consolidation chemotherapy immediately after the first complete remission. The chemotherapy included either 4 courses of high dose Arac (HiDAC), 3 gm/m2 q12h x3 days, or 2 courses of HiDAC (4 days) plus mitoxantrone for 3 days and etoposide for 7 days (HiDAC-3-7). Granulocyte colony-stimulating factor (G-CSF) used used 24 hours after chemotherapy until absolute neutrophile count greater than 500/mm3. RESULTS: Totally 24 courses of high dose chemotherapy were given. The median duration of severe neutropenia (absolute neutrophile count < or = 500/mm3) was 12 days, thrombocytopenia (< or = 50,000/mm3) 18 days, fever > or = 38 degrees C 6 days, and from severe neutropenia (absolute neutrophile count < or = 500/mm3) was 12 days, thrombocytopenia (< or = 50,000/mm3) 18 days, fever > or = 38 degrees C 6 days, and from severe neutropenia (< or = 500/mm3) to infection 4 days. Infection was the most frequent complication during HiDAC treatment. No toxic death was noted. After a median follow-up of 16 months, early relapse was noted in 3 patients (2, 4, and 5 months, respectively), and late relapse in two patients (11 and 20 months, respectively). Seven patients remained in complete remission status after a median follow-up of 14+ months (7+ to 37+ months). CONCLUSIONS: Intensive consolidation chemotherapy is well tolerable and may prolong remission duration when used in the early post-remission phase of AML.

Induction of megakaryocytic differentiation in a newly established human leukemic cell line by 12-o-tetradecanoylphorbol-13-acetate.

BACKGROUND: Biological studies on megakaryopoiesis have been hampered by the scarcity of megakaryocytes in normal bone marrow and difficulty in long term culture. Alternatively, leukemic cell lines with megakaryocytic differentiation potential may provide good models to counter these problems. METHODS: Leukemic cells from a patient with acute megakaryocytic leukemia were put into long-term culture and established into a cell line which was designated as VGH-MK1. The VGH-MK1 cells were challenged with differentiation agents and/or cytokines, and the differentiation of these cells was examined using morphological, immunocytochemical and surface-marker studies. RESULTS: Morphologically, VGH-MK1 cells had prominent nucleoli and basophilic cytoplasm with some protrusions, but large cells were occasionally seen. Under regular culture condition, the cells had a doubling time of 36-48 hours. The cloned cell line exhibited markers characteristic of megakaryoblasts after differentiation induction. Specifically, when stimulated with 12-o-tetradecanoylphorbol-13-acetate (TPA), cells became larger and had large or multinuclei. They were induced to express platelet glycoproteins GPIb (CD42b), GPIIb/IIIa (CD41), and GPIIIa (CD61) antigens, but not erythroid nor lymphoid markers. Platelet peroxidase (PPO) activity was also induced. Retinoic acid did not exhibit similar differentiation-inducing effects. In contrast, it counteracted the effects induced by TPA. CONCLUSIONS: An unique human leukemic cell line, VGH-MK1, has been established here. It could be induced to exhibit some characteristics of megakaryocytic lineage, and may be an useful model for the biological studies of megakaryopoiesis.

Recombinant human granulocyte colony-stimulating factor infusion and/or autologous peripheral blood stem cell transplantation as a rescue for sequential high-dose combination chemotherapy: a preliminary report.

BACKGROUND: Sequential cycles of combination chemotherapy with high-dose cyclophosphamide, etoposide and cisplatin (sHDCEP) can largely increase the total dose (TD) of drug delivered. If granulocyte colony-stimulating factor (G-CSF) and/or autologous peripheral blood stem cell (PBSC) rescue can shorten the duration of cytopenia between cycles of sHDCEP, the dose intensity (DI) can be increased as well. In order to explore the feasibility of delivering maximal TD and DI by administration of sHDCEP with G-CSF and/or PBSC rescue, this trial is undertaken to investigate the hematologic and nonhematologic toxicity observed with sHDCEP by G-CSF and/or PBSC rescue. METHODS: Patients with refractory malignancy and well preserved physiologic function for whom no available therapy is likely to cure or prolong the survival were eligible for the study. Each cycle of high-dose chemotherapy consisted of: cyclophosphamide 5,000 mg/m2, etoposide 1,500 mg/m2 and cisplatin 150 mg/m2. G-CSF and/or PBSC were administered alternatively after each cycle as rescue for myelosuppression. The next cycle was given to patient who showed response to the previous cycle after recovery from toxicity for a maximal of 4 cycles. RESULTS: Two cases of refractory malignancy with progressive disease were treated by sHDCEP for 7 cycles, including 4 cycles with G-CSF rescue, 2 cycle with PBSC rescue, and 1 cycle with G-CSF + PBSC rescue. In the 4 cycles rescued by G-CSF alone, we observed a slightly slower granulocyte and markedly prolonged platelet recovery in the subsequent cycle. By comparing the effect of G-CSF and/or PBSC rescue on hematologic recovery with the preceding cycle in the same patient, we found that G-CSF rescue provided faster granulocyte recovery than PBSC, but PBSC rescue provided faster platelet recovery than G-CSF. Rescue by larger number of PBSCs provided only faster platelet but not granulocyte recovery than rescue by adding G-CSF to a very small number of PBSCs. However, G-CSF plus the very small number of PBSCs provided shorter duration of both granulocytopenia and thrombocytopenia than rescue by G-CSF alone. The most common nonhematologic toxicity from sHDCEP included transient nausea, vomiting, diarrhea and mild impairment of liver function but we observed no significant or irreversible major organ damage. The side effect from PBSC collection was mild and toxicity from reinfusion of the thawed PBSCs was not obvious. Using G-CSF and/or PBSC rescue, sHDCEP was delivered repeatedly in no more than 4 weeks for the next-cycles except for patient 1 who had cycle 4 delayed because of prolonged platelet recovery by only G-CSF rescue in cycle 3. CONCLUSIONS: Our initial experience has shown that the nonhematologic toxicity from sHDCEP, G-CSF and PBSC rescue was well tolerated. Prolonged platelet recovery after sequential cycles of HDCEP by only G-CSF rescue delayed the next cycle of chemotherapy. Although the next cycle was delivered within 4 weeks by only PBSC rescue, concurrent infusion of G-CSF and larger number of PBSCs should provide the most rapid hematologic recovery. Sequential high-dose chemotherapy administered by this model is likely to provide the maximal delivery of TD and DI, and is worthy of further clinical trials.