Louis Tak Lui

Nasopharyngeal cancer: Study III. A review of 1206 patients treated with combined modalities

A combination of radiation therapy and chemotherapy was used in an attempt to improve the control of nasopharyngeal cancer (NPC). From 1979 through 1983, 1206 patients with histologically proven NPC were treated with routine radiation along with 5 combinations of drug or drugs in small to maintenance doses. The drugs used were: 1) cyclophosphamide p.o. (CTX), 2) methotrexate p.o. (MTX), 3) CTX + MTX, 4) bleomycin i.v. (BLM), and 5) cisplatin + BLM i.v. (BP). The actuarial survival rates and recurrence rates were chosen as endpoints for comparison to previous studies. The overall survival rate increased from 43.5% in study I, and 56% in study II to 70.6% in the present study. The recurrence rate declined to 13%, but was less impressive. The encouraging results were more obvious in groups of patients with bilateral large cervical lymph nodes, reaching statistical significance (p less than 0.01).

Impact of magnetic resonance imaging versus CT on nasopharyngeal carcinoma: Primary tumor target delineation for radiotherapy

Our aim was to assess the capacity of CT versus MRI for delineating to the primary tumor extent of nasopharyngeal carcinoma (NPC) in treated patients.

Induction Chemotherapy With Mitomycin, Epirubicin, Cisplatin, Fluorouracil, and Leucovorin Followed by Radiotherapy in the Treatment of Locoregionally Advanced Nasopharyngeal Carcinoma

PURPOSE Survival in advanced nasopharyngeal carcinoma (NPC) is compromised by distant metastasis. Because mitomycin is active against hypoxic and G0 cells, which may help to eradicate micrometastasis, we investigated the effect of mitomycin-containing cisplatin-based induction chemotherapy. PATIENTS AND METHODS Recruited for this study were American Joint Committee on Cancer (AJCC) 1992 staging system stage IV NPC patients with the following adverse features: obvious intracranial invasion, supraclavicular or bilateral neck lymph node metastasis, large neck node (> 6 cm), or elevated serum lactate dehydrogenase (LDH) level. Patients were given three cycles of chemotherapy before radiotherapy. The chemotherapy comprised a 3-week cycle of mitomycin, epirubicin, and cisplatin on day 1 and fluorouracil and leucovorin on day 8 (MEPFL). RESULTS From January 1994 to December 1997, 111 patients were recruited. The median follow-up period was 43 months. The actuarial 5-year overall survival rate was 70% (95% confidence interval [CI], 60% to 80%; n = 111). For patients having completed radiotherapy (n = 100), the 5-year locoregional control rate was 70% (95% CI, 55% to 84%) and the distant metastasis-free rate was 81% (95% CI, 73% to 89%). The 5-year distant metastasis-free rate of N3a and N3b disease of AJCC 1997 staging system were 79% (95% CI, 62% to 95%) and 74% (95% CI, 60% to 89%), respectively. By Cox multivariate analysis, high pretreatment serum LDH level (P = .04) and neck nodal enlargement before radiotherapy (P = .001) were adverse prognostic factors of survival. CONCLUSION The good 5-year survival of N3 disease supports the effectiveness of induction MEPFL in the primary treatment of advanced NPC. Further investigation to incorporate concurrent chemoradiotherapy is warranted.

Dysphagia in Patients with Nasopharyngeal Cancer After Radiation Therapy: A Videofluoroscopic Swallowing Study

This study evaluated swallowing status and the factors influencing swallowing in patients with nasopharyngeal carcinoma (NPC) after radiation therapy. During the period from July 1995 to June 1999, this cross-sectional study used videofluoroscopic swallowing study (VFSS) to evaluate 184 NPC patients who had completed radiation therapy [113 cases had completed radiation therapy ≤12 months prior to evaluation (acute group) and 71 cases had completed radiation therapy >12 months prior to evaluation (chronic group)]. The numbers of patients with tumors in each of the four stages were as follows: 24 in stage I, 45 in stage II, 41 in stage III, and 74 in stage IV. Swallowing abnormalities of the acute and chronic groups were correlated with multiple variables, including gender, age, the stage of the tumor, use of either neoadjuvant chemotherapy or radiosensitizer, and radiation modality. The analytical results indicated that the chronic group had a significantly higher proportion of swallowing abnormalities. Radiation modality, chemotherapy, and tumor staging were not significantly associated with swallowing dysfunction. Trend analysis revealed a progressive deterioration of most parameters of swallowing function in this group of patients. These findings indicate that swallowing function continues to deteriorate over time, even many years after radiation therapy in patients with NPC. Our results indicate that the time elapsed since radiation therapy correlates with the severity of dysphagia in NPC patients.

Experience of radiotherapy in lethal midline granuloma with special emphasis on centrofacial T-cell lymphoma: a retrospective analysis covering a 34-year period

Lethal midline granuloma (LMG) is characterized by progressive ulceration and destruction of the midfacial tissue. It occurs more frequently in Oriental than in Western populations. Because of the progress in clinical pathology and immunohistochemistry, most cases have been proven to be malignant lymphomas, especially of T-cell lineage. We describe 92 cases of lethal midline granuloma or centrofacial malignant lymphoma in the period 1959-1993. All received complete courses of radiotherapy. Twenty of them also received combination chemotherapy. Thirty-six cases had specimens available for immunohistochemical study; 25 (69%) of these had a T-cell phenotype, and 6 (17%) were of B-cell lineage. The dose to the nasal region was in the range of 3000-7500 cGy in 11-58 days, and to the neck 3000-6400 cGy in 11-48 days. The overall survival rate for the LMGs was 59.5% at 5 years and 56.2% at 10 years (Kaplan-Meier). Combined chemotherapy seemed not to improve the overall survival in this study (p = 0.63), but the patient number was too small to make a firm conclusion. Based on the results of this study, we recommend a dose of 4500-5000 cGy to the midfacial region, since a higher dosage did not improve the treatment results (p = 0.88). Irradiation has a definite role in good locoregional control of this disease. The recent clarification of the disease nature and the recognition of the background clinicopathological features should provide valuable information for future patient management and prospective studies.

Gemcitabine and cisplatin in a multimodality treatment for locally advanced non-small cell lung cancer.

The role of new cytotoxic agents like gemcitabine has not yet been proven in the neoadjuvant settings. We designed a phase II study to test the feasibility of using gemcitabine and cisplatin before local treatment for stage III non-small cell lung cancer patients. Patients received three cycles of induction chemotherapy of gemcitabine (1000 mg m−2, days 1, 8, 15) and cisplatin (90 mg m−2, day 15) every 4 weeks before evaluation for operability. Operable patients underwent radical resection. Inoperable patients and patients who had incomplete resection received concurrent chemoradiotherapy with daily low dose cisplatin. All patients who did not progress after local treatment received three more cycles of adjuvant chemotherapy of gemcitabine and cisplatin. Fifty-two patients received induction treatment. Two patients had complete response and 31 patients had partial response (response rate 63.5%) after induction chemotherapy. Thirty-six patients (69%) were operable. Eighteen patients (35%) had their tumours completely resected. Two patients had pathological complete response. Median overall survival was 19.1 months, projected 1-year survival was 66% and 2-year survival was 34%. Three cycles of gemcitabine and cisplatin is effective and can be used as induction treatment before surgery for locally advanced non-small cell lung cancer patients.

Preliminary Results of Fractionated Stereotactic Radiotherapy in Patients with Advanced Hepatocellular Carcinoma

Purpose: The treatment result of advanced hepatocellular carcinoma failed from previous TACE is often unsatisfactory. To minimize the acute and late adverse effects of liver irradiation and preserve maximal normal liver tissue, fractionated stereotactic radiotherapy (R/T) is used in our institute. Materials & Methods: Twenty-three patients with advanced hepatocellular carcinoma received fractionated stereotactic radiotherapy with 55Gy in 22 fractions. All patients were assessable for side effects and response. Results: The mean regression of turner volume was 29% at 1 month after completion of R?T, 41% at 2 months and 55% at 3 months. In 17 patients with elevated serum alpha-fetoptein (AFP), 15 (88%) were found to have response in the first month after R/T, 10 (59%) had regression of more than 50% of the original level at the first month after R/T. Conclusion: For patients with advanced hepatocellular carcinoma, the fractionated stereotactic radiotherapy is a feasible modality and deserves further follow-up for outcome and toxicity.

High-dose therapy with peripheral blood stem cell (PBSC) support using an innovative mobilization regimen in patients with high-risk primary or chemoresponsive metastatic breast cancers

High-dose therapy followed by peripheral blood stem cell (PBSC) support was performed in 29 patients with primary high-risk (Group I) or chemoresponsive metastatic (Group II) breast cancer patients. Group I patients had received PBSC mobilization within 4 weeks of modified radical mastectomy. Group II patients had to achieve minimal residual disease (MRD) by induction chemotherapy before being considered eligible for PBSC mobilization and high-dose therapy. An innovative FE120C regimen (5-FU 600 mg/m2, i.v., day 1; epirubicin 120 mg/m2, i.v., day 1; cyclophosphamide 600 mg/m2, i.v., day 1) plus G-CSF (300 μg/day, subcutaneous injection for 9 days, from day 4 post-FE120 C) was used to mobilize PBSCs. After high-dose CTCb (cyclophosphamide 6,000 mg/m2, thiothepa 500 mg/m2, carboplatin 800 mg/m2, in 4 days), patients received PBSC infusion and daily C-CSF 300 μg sub cutaneous injection.There were 19 and 16 patients enrolled into Group I and Group II, respectively. Ten of the Group II patients had achieved minimal residual disease (MRD) after induction chemotherapy. The median numbers of mobilized total CD34 + cells for Group I and Group II patients were 27.3 (9.2 to 114.1) × 106/kg and 17.1 (5.9 to 69.1) × 106/kg respectively. The median time to neutrophil recovery (ANC ≥ 500/μL) was 8 and 9 days in Group I and II, respectively. The median time to platelet recovery (≥ 50,000/μL) was 10 and 15 days in Group I and II, respectively. No major treatment-related toxicities were noted. In Group I, 13 out of 19 patients (68.4%; 43–87%, 95% C.I.) remained recurrence-free with a median follow-up of 31 months (6 + to 55 + months). In Group II, 3 out of 10 patients (30%; 7–65%, 95% C.I.) remained progression-free at 33 +, 35 +, 39 + months from induction therapy.We suggest that the FE120C plus G-CSF is an effective and innovative regimen for PBSC mobilization in breast cancer patients, and high-dose CTCb therapy with PBSC support is a safe and well-tolerated treatment modality.

Cell kinetics and radiosensitivity of cervical squamous cell carcinoma

Flow cytometry analyses of tumors from 12 patients with cervical squamous cell carcinoma under radiotherapy were performed in this preliminary study. Six patients with a high (> 10%) G2/M fraction before treatment showed greater than 50% tumor reduction after initial 2000 cGy radiotherapy. Only two out of six patients with a low (< 10%) G2/M fraction before treatment responded favorably and three of them already had recurrence during the follow-up period of 33-40 months. Hyperploidy (DNA index > 1.1) was observed in 5 patients; all of them responded well to radiotherapy in contrast to three out of seven diploid tumors.

Allogeneic bone marrow transplantation for children with acute lymphoblastic leukemia in second remission or relapse.

Most children with acute lymphoblastic leukemia (ALL) are successfully treated by chemotherapy. For those patients, who relapse on therapy, bone marrow transplantation (BMT) is considered most appropriate after a subsequent remission is achieved. Three boys with ALL aged from 9 to 13 years met these criteria and received BMT from their HLA-compatible sisters after marrow ablation with total body irradiation 12 Gy plus high dose cytosine arabinoside 3 gm/m2/12h x 12 doses and graft-versus-host disease (GVHD) prophylaxis with cyclosporine plus short course methotrexate from March 10, 1989 to May 23, 1992. Filgrastim (rhG-CSF) was used to hasten the recovery of granulocyte in one patient. All three patients got full engraftment and two had grade 1 acute GVHD. None of them developed chronic GVHD. Two patients have disease-free survival over 51 and 12 months respectively post BMT without further chemotherapy. One patient died of recurrent refractory leukemia 5 months after BMT. The toxicity of this conditioning regimen included photophobia, conjunctivitis and erythematous skin rashes. One patient who received filgrastim from day 1 to 21 developed severe bone pain. However, this patient had faster recovery of granulocyte count than the other two patients. The preliminary results of this work favors BMT for children with recurrent ALL whose ultimate survival is usually poor when treated with chemotherapy. Further efforts are necessary to investigate new methods for reducing leukemic relapse in ALL patients undergoing BMT.