Phase II study: concurrent chemo-radiotherapy in advanced nasopharyngeal carcinoma

Oesophageal carcinoma is a major cause of cancer death in certain parts of the world. Early detection provides the only chance of cure. In this study, one female and nine male patients with superficial oesophageal carcinoma were investigated to determine the pertinent clinical and pathological features. All male patients were smokers and six patients drank various amounts of alcohol on a daily basis. Histologically, five cases were confined within the mucosal layer and five within the submucosal layer. All five mucosal cancer cases and two of the five submucosal cancer cases were asymptomatic. Endoscopically, all five mucosal cancer patients had flat lesions, whereas the five submucosal cancer tumours appeared either protruding or depressed. Barium oesophagography failed to demonstrate the lesions in four of five mucosal cancer and one of five submucosal cancer cases. Endoscopic ultrasonography correctly detected the depth of cancer invasion in six out of eight superficial oesophageal carcinoma cases. All patients received a one-stage operation that included oesophagectomy and lymph node dissection. All five mucosal cancer patients had no lymph node involvement and have experienced no tumour recurrence. Among them, one who had concomitant hepatocellular carcinoma died early. Of the five submucosal cancer cases, four died 1-5 years after the operation. It is concluded that oesophageal carcinoma is curable in its early stage. Physicians should be alert while performing endoscopic examination. We believe that the dyeing technique is a useful adjunct to endoscopic examination.     

Management of carcinoma anal canal with combination chemotherapy and concurrent radiotherapy

Results of 21 cases of squamous cell carcinoma of anal canal treated by continuous infusion of 5-fluorouracil 1000 mg/sqm for 4 days and mitomycin-C 15 mg/sqm on 1st day by i.v. route with concurrent external beam radiotherapy of 42 Gy from 1st day of chemotherapy were analysed. Out of 21 patients, 16(76.19%) achieved complete remission, 3 (14.28%) partial remission and 2 (9.52%) cases did not respond at all. On follow-up, 7 (33.33%) histopathological positive cases needed abdominoperineal resection with good recovery. After 2 years of follow-up 14 (66.67%) cases were free from the disease and 3 (14.28%) were alive with the disease. The median duration of follow-up was 36 months.     

Radiotherapy and concurrent chemotherapy for the treatment of locally advanced head and neck squamous cell carcinoma

PURPOSE: To determine whether combination 5-fluorouracil, cisplatin, and interferon alfa, an active regimen in advanced esophageal cancer, is efficacious as induction therapy before esophagectomy. MATERIALS AND METHODS: Forty-four patients with potentially resectable esophageal/gastroesophageal junction adenocarcinoma or squamous cell carcinoma were entered into a phase I/II study of this chemotherapeutic regimen and concurrent external-beam radiotherapy before resection. The initial 16 patients were treated with prolonged-infusion 5-fluorouracil (300 mg/m2 on days 1 to 28), cisplatin (20 mg/m2 on days 1 to 5 and 24 to 28), interferon alfa (3 x 10(6) U/m2 intravenously on days 1 to 5 and 24 to 28; subcutaneous injection every other day on days 6 to 23), and radiation (4000 cGy). The subsequent 28 patients were treated over 21 days with two modifications: dose escalation of 5-fluorouracil (250 to 350 mg/m2) and double-fractionated radiotherapy to a total dose of 4500 cGy. RESULTS: Forty-one patients completed chemoradiotherapy and were evaluable for toxicity. Adverse events were substantial but tolerable, and most toxic episodes were hematologic and gastrointestinal. Three patients died, and one patient had progressive disease before resection. Of the 37 patients eligible for curative resection, 36 had all gross tumor removed. Thirty-three (80%) patients had a major pathologic response: 10 (24%) with no residual tumor and 23 with only microscopic residual tumor. Median survival for all patients was 27 months and for responders was 36 months. CONCLUSIONS: This combination regimen is active but yields results similar to those of other chemoradiotherapy phase II trials; therefore, the contribution of interferon alfa to treatment efficacy remains uncertain. The true worth of preoperative chemoradiotherapy is unknown pending results of phase III trials.     

A pilot evaluation of alternating preoperative chemotherapy in the management of patients with locoregionally advanced breast carcinoma

BACKGROUND: This prospective trial was conducted to evaluate the outcome of patients treated with preoperative and post operative chemotherapy, mastectomy, and irradiation for locoregionally advanced breast carcinoma. METHODS: Between June 1986 and September 1990, 71 patients received 2 cycles of doxorubicin that alternated with 2 cycles of cyclophosphamide, methotrexate, and 5-fluorouracil prior to mastectomy; irradiation was administered when the tumor was not amenable to surgical resection. Additional chemotherapy and tamoxifen, in hormone receptor-positive tumors, was used after mastectomy. Post-operative irradiation was given on a selective basis for patients at high risk for locoregional disease recurrence. RESULTS: Although 5 patients (7%) had disease progression, clinical partial or complete tumor response to preoperative chemotherapy was noted in 46 patients (65%). Sixty-eight patients (96%) underwent mastectomy. With a median follow-up of 52 months, the relapse-free and overall survival rates at 5 years were 42% and 57% respectively. Locoregional tumor recurrence occurred in 14 patients (20%), and 28 patients (39%) developed metastatic disease. Menopausal status, clinical presentation (noninflammatory vs. inflammatory), and American Joint Committee on Cancer clinical stage were independent covariates associated with patient outcome. CONCLUSIONS: Preoperative alternating chemotherapy, with the selective use of irradiation, resulted in significant locoregional disease regression and the successful integration of mastectomy into the therapeutic strategy. Locoregional tumor control and relapse-free and overall survival estimates for the approach described herein compared favorably with other comtemporary reports for this condition.     

Advanced nasopharyngeal carcinoma treated with chemotherapy and radiotherapy: distant metastasis and local recurrence

BACKGROUND: Resuscitation guidelines caution against extreme extension or flexion of an infant's head because tracheal obstruction may occur. No data support this recommendation. The authors therefore examined the dimensions of the tracheal lumen in neutral, extended, and flexed head positions in infants undergoing general endotracheal anesthesia for elective surgery. METHODS: Eighteen healthy full-term infants were studied. A flexible fiberoptic bronchoscope was passed through a previously inserted endotracheal tube and positioned above the cricoid cartilage. Video recordings were taken in each of three head positions. Recordings were analyzed by an investigator blinded to head position. A computer-digitized technique was used to measure anterior-posterior and lateral dimensions and cross-sectional area. Data were analyzed using paired t tests and sign tests. RESULTS: No significant differences in mean tracheal dimensions with changes in head position were found. No infant had complete tracheal obstruction. Infants were equally as likely to have a small increase as they were to have a small decrease in tracheal dimension with changes in head position. CONCLUSIONS: Despite the belief that infants and neonates have obstruction at the level of the trachea with extreme positions of the head, the authors were unable to demonstrate this phenomenon.     

调强放疗结合腔内放疗同步化疗治疗中晚期宫颈癌的临床观察

目的 研究调强放疗、腔内治疗并同步化疗治疗中晚期(IIB-ⅢB)宫颈癌的疗效及毒副反应.方法 选择宫颈癌患者60例,随机分为调强组(调强放疗,腔内放疗结合同步化疗,30例),常规组(常规四野箱式外照射,腔内放疗结合同步化疗,30例).治疗方法:调强组给予56～60 Gy剂量,常规组予50～54 Gy盆腔照射.腔内放疗:A点给予5 Gy/次,2次/周,共6～8次.所有病人接受多西他赛和顺铂同步化疗,每3周一次,共3个疗程.比较临床疗效和急性、晚期毒副反应.结果 两组病人资料类似.中位随访时间是47个月.调强组与常规组的1,2,3年生存率分别为90.0%,86.7%,80.0%以及86.7%,70.0%,60.0%;两组比较差异没有显著性(P>0.05).调强组中有7例(23.33%)患者复发,常规组有17例(56.67%)复发,两组比较差异有统计学意义(P＜0.05).常规组中3,4级急性和晚期消化道反应和泌尿道反应的发生率比调强组高,差异有统计学意义(P＜0.05).血液骨髓毒副反应的比较,两组结果相似.结论 调强放疗结合腔内放疗并同步多西他赛、顺铂化疗,是治疗局部晚期宫颈癌有效的方法.     

Preliminary report of the Asian-Oceanian Clinical Oncology Association randomized trial comparing cisplatin and epirubicin followed by radiotherapy versus radiotherapy alone in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma. Asian-Oceanian Clinical Oncology Association Nasopharynx Cancer Study Group

BACKGROUND: The aim of this trial was to compare the outcome achieved with neoadjuvant chemotherapy followed by radiotherapy to that achieved with radiotherapy alone for patients with locoregionally advanced undifferentiated or poorly differentiated nasopharyngeal carcinoma (NPC) meeting one of the following criteria: Ho's T3 disease, Ho's N2-N3 disease, or lymph node size > or =3 cm. METHODS: Between September 1989 and August 1993, 334 patients were enrolled in the study, with equal numbers of patients randomized to the neoadjuvant chemotherapy arm (CT arm) and the radiotherapy arm (RT arm). Neoadjuvant chemotherapy consisting of 2-3 cycles of cisplatin (60 mg/m2 on Day 1) and epirubicin (110 mg/m2 on Day 1) followed by radiotherapy was given to the CT arm. For radiotherapy, a dose of 66-74 gray (Gy) (median, 71 Gy) was delivered to the primary tumor and 60-76 Gy (median, 66 Gy) to the neck. Two hundred eighty-six eligible patients completed the treatment and were evaluable for treatment response (134 in the CT arm, 152 in the RT arm). All patients were included in the survival analysis based on the intention to treat. The median follow-up was 30 months for the whole cohort and 41 months for the surviving patients. RESULTS: Analysis of the 334 patients based on the intention to treat showed no significant difference in relapse free survival (RFS) or overall survival (OS) between the 2 treatment arms (3-year RFS rate: 48% in the CT arm vs. 42% in the RT arm, P = 0.45; 3-year OS rate: 78% vs. 71%, P = 0.57). In an efficacy analysis based on only the 286 evaluable patients, a trend of improved RFS favoring the CT arm was observed (3-year RFS rate: 58% vs. 46%, P = 0.053), with again no significant difference in OS (3-year OS rate: 80% vs. 72%, P = 0.21). In the subgroup of 49 patients with bulky neck lymph nodes >6 cm, improved RFS (3-year RFS rate: 63% vs. 28%, P = 0.026) and OS (3-year OS rate: 73% vs. 37%, P = 0.057) were observed, favoring the CT arm. CONCLUSIONS: This multicenter randomized study did not demonstrate any benefit with the addition of cisplatin-epirubicin neoadjuvant chemotherapy for patients with locoregionally advanced nasopharyngeal carcinoma; therefore routine administration of neoadjuvant chemotherapy to this target group cannot be recommended. Although the overall incidence of recurrence was reduced with the addition of chemotherapy in the efficacy analysis, the overall survival was not affected. A more effective chemotherapy regimen, the selection of an appropriate target group, and the use of an alternative strategy for combining chemoradiotherapy should be explored in future trials.     

Volumetric analysis of tumor extent in nasopharyngeal carcinoma and correlation with treatment outcome

PURPOSE: To investigate the variability of tumor volume in nasopharyngeal carcinoma using quantitative measurements of tumor bulk derived from computed tomography, and to study the prognostic value of tumor volume in comparison with other variables. METHODS AND MATERIALS: Two hundred ninety patients with newly diagnosed nasopharyngeal carcinoma were included in the study. The primary tumor volume (PTV) and nodal tumor volume (NTV) were obtained by outlining the tumor contour followed by summation of areas in sequential pretreatment computed tomography axial scans. Total tumor volume (TTV) was obtained by adding the PTV and NTV. All patients had radiotherapy as the primary treatment, 67 patients also received cisplatin-based neoadjuvant chemotheraphy. RESULTS: A large variation in tumor volume was observed, especially in advanced stage disease. The median PTV (cc) in Ho's T1, T2, and T3 disease were: 6.9 (range: 0.9-42.7), 18.8 (1.6-127.9), and 52.4 (3.3-166.8). The median TTV (cc) in Ho's stage I to IV disease were: 7.6 (range: 1.3-42.7), 19.8 (3.2-55.7), 40.7 (4.1-222.7), and 51.1 (3.1-274.7). Patients with a large PTV (>60 cc) were associated with significantly poorer local control (5-year local control rate: 56%) and disease-specific survival (5-year survival rate: 53%). In patients with a small PTV (< or =20 cc), there were no significant differences in local control among different T stages. Large NTV (>30 cc) was associated with significantly higher distant failure rate (5-year distant relapse-free survival rate: 54%) and lower disease-specific survival (5-year survival rate: 40%). In multivariate analysis, only PTV was found to be an independent factor in predicting local control. CONCLUSION: A large variation of tumor volume was present in different T stage disease of nasopharyngeal carcinoma, and PTV represents an independent prognostic factor of local control that appears to be more predictive than Ho's T stage classification.     

Prognostic expectations and treatment outcome.

Studied the relationship between recovery (symptom reduction) from serious psychiatric disorder and patient-held and therapist-held expectations for recovery. Objective measures of prognostic expectations were taken from 150 patients (mean age, 32.6 yrs) upon hospital admission and from 14 staff therapists shortly thereafter. Expectations stated by both groups were factor analyzed, and 2 sets of 6 weighted factor scores were calculated for each patient. Multiple regression analyses were employed to test for association between sets of factor scores and symptom reduction through hospitalization. Changes in MMPI and Brief Psychiatric Rating Scale scores (admission to discharge) were used as measures of symptom reduction. It was found that therapists', but not patients', expectations were reliably associated with symptom reduction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The long-term outcome after radical radiotherapy for advanced localized non-small cell carcinoma of the lung

Forty six patients that underwent below knee amputation for diabetes, trauma/osteomyelitis or peripheral vascular disease were studied. Healing was estimated by the rate of progression through temporary prostheses as determined weekly by the amputee rehabilitation team (physiatrist, orthopedist, physical therapist, nurse, and prosthetist). For all groups combined, mean days +/- standard error from amputation to above knee cast with pylon and foot (AKPy) were 22.9 +/- 1.9, to below knee cast with pylon and foot (BKPy) 41.6 +/- 2.8 and to laminated temporary prostheses 66.5 +/- 4.5. A regression analysis of these variables on age (range: 29 to 84 yr) showed significant positive correlations for AKPy (r = 0.34, P = 0.0214) and BKPy (r = 0.40, P = 0.0056). An analysis of variance with contrasts (Tukey's protected t) showed significant lower values (P < 0.05) for amputation to BKPy in the trauma/osteomyelitis group when compared to diabetes or peripheral vascular disease and no difference among the last two groups. However, when variables were adjusted for age (analysis of covariance with age as a covariate), the differences among groups disappeared (covariance F(2,44) = 0.9, P > 0.4). In conclusion, age, not the cause of the amputation, correlated with healing after below knee amputation as estimated by the rate of progression through temporary prostheses.     

Prognostic factors in endometrial carcinoma: risk groups and adjuvant radiotherapy

Prognostic factors for disease-free survival in patients with endometrial carcinoma have been retrospectively assessed in 611 cases diagnosed, treated and followed at our institution between 1971 and 1990. Age, symptoms, comorbidity, FIGO clinical stage, and hysterectomy, as well as size and location of the tumor, histologic type, FIGO grade, myometrial invasion, lympho-vascular invasion, and final surgical stage have all been evaluated by univariate and multivariate methods. A mathematical predictive model has been applied to define risk groups, and the applied adjuvant treatments have been evaluated according to these groups. One hundred and thirty-one patients were not treated primarily with surgery, and the actuarial 5 and 10-year disease-free survival was 51.6% and 34.7% respectively. Only clinical stage (FIGO 1971) and modality of radiotherapy were significant prognostic factors. For the 480 patients treated primarily by surgery, independent prognostic factors for 5 and 10-year disease-free survival in multivariate analysis were extrauterine spread, absence of diagnostic comorbidity, FIGO grades 2-3, lympho-vascular invasion, age > 65 years and cervical extension. Five and 10-year disease-free survival was 81.5% and 73.4% respectively. Three risk groups were obtained, whose survival was not affected by the adjuvant treatments applied.     

Carboplatin-based versus cisplatin-based chemotherapy in the treatment of surgically incurable advanced bladder carcinoma

BACKGROUND: The carboplatin-based chemotherapeutic regimen M-CAVI (methotrexate, carboplatin, and vinblastine) is active against bladder carcinoma and can be administered to patients who are ineligible to receive cisplatin or doxorubicin. The authors designed a randomized study to evaluate whether M-CAVI offers a therapeutic advantage over the cisplatin-based regimen M-VAC (methotrexate, vinblastine, doxorubicin, and cisplatin) in the treatment of patients with surgically incurable advanced bladder carcinoma. METHODS: Patients with surgically incurable advanced bladder carcinoma were enrolled on a randomized trial comparing M-CAVI, which consists of carboplatin (300 mg/m2 on Day 2, adjusted using Calvert's formula for an area under the curve of 5), methotrexate (30 mg/m2 on Days 1, 15, and 22), and vinblastine (3 mg/m2 on Days 2, 15, and 22) administered every 28 days, versus standard M-VAC. The eligibility criteria included histologically proven bladder carcinoma, surgically incurable disease, and no prior chemotherapy. Patients were treated until disease progression or unacceptable toxicity occurred. RESULTS: From January 1989 to January 1994, 47 assessable patients were included. Seventeen patients had lymph node disease and 30 had distant metastatic disease. Twenty-three patients were randomized to receive M-CAVI and 24 to receive M-VAC. Patient characteristics in the two groups were similar. Overall response rates were 39% (95% confidence interval [CI], 20-62%) for M-CAVI and 52% (95% CI, 30-73%) for M-VAC (P = 0.3), with 3 complete responses observed among patients treated with M-VAC and none among those in the M-CAVI group. M-VAC was associated with more gastrointestinal toxicity, stomatitis, alopecia, and Grade 4 neutropenia than M-CAVI. One toxicity-related death occurred in the M-VAC group. There was a statistically significant difference in median disease-related survival time favoring M-VAC (16 months; range, 6 to 22+) versus M-CAVI (9 months; range, 6 to 14+) (P = 0.03). CONCLUSIONS: M-CAVI is less toxic but less active than M-VAC in the treatment of patients with advanced bladder carcinoma. Carboplatin-based regimens in which carboplatin is administered at the dose range used in the current study should be reserved for patients who cannot tolerate cisplatin treatment. Further research is required to assess the impact of high dose carboplatin in the treatment of this disease.     

The role of chemotherapy in the management of nasopharyngeal carcinoma

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a radiosensitive tumor for which there is a high local control rate after radical radiotherapy (RT). However, for patients with locoregionally advanced disease, the rate of distant metastasis is high and the 5-year overall survival rate is poor. METHODS: A review of retrospective and prospective clinical studies was performed to assess the role of chemotherapy in three settings: metastatic disease; neoadjuvant and/or adjuvant; and concurrent chemotherapy with radiotherapy. RESULTS: Cisplatin-based combination chemotherapy results in a high response rate in patients with metastatic NPC, and a subgroup may achieve long term disease free survival. The use of neoadjuvant and adjuvant chemotherapy to treat locoregionally advanced disease has resulted in consistently high response rates, but no randomized trial to date has demonstrated an improvement in overall survival. A recent Head and Neck Intergroup study randomized patients in the United States to receive concurrent chemotherapy (cisplatin) and radiotherapy or radiotherapy only. Although this approach demonstrated significant benefit in overall survival favoring the use of concurrent chemotherapy and radiotherapy, its applicability in geographic areas of high NPC incidence remains to be proven. CONCLUSIONS: NPC is a chemosensitive tumor, and patients with metastatic disease have a high response rate. Further prospective studies will define the standard approach to treating locoregionally advanced NPC, which is likely to incorporate into the primary treatment some form of systemic chemotherapy.     

Vinorelbine as neoadjuvant chemotherapy in advanced cervical carcinoma

PURPOSE: To evaluate the efficacy and toxicity of vinorelbine (VNB) as single-agent neoadjuvant chemotherapy in advanced cervical carcinoma (ACC). PATIENTS AND METHODS: Between December 1993 and October 1995, 43 untreated patients with stages IIB to IVA squamous cell cervical cancer were entered onto this study. Forty-two patients are assessable for response and 43 for toxicity. The median age was 46 years (range, 28 to 65). Distribution by stages (International Federation of Gynecology and Obstetrics [FIGO]) was as follows: IIB, 18 patients; IIIA, one; IIIB, 19; and IVA, five. Therapy consisted of VNB 30 mg/m2 by 20-minute intravenous (IV) infusion repeated weekly for 12 injections and followed by radical surgery if feasible or definitive radiotherapy. Both staging and response assessment were performed by a multidisciplinary team. RESULTS: One patient was considered not assessable for response. A total of 493 cycles of therapy were administered and objective remissions were observed in 19 of 42 patients (45%; 95% confidence interval, 30% to 60%). Two patients (5%) had a complete response (CR) and 17 (40%) a partial response (PR); no change (NC) was observed in 16 (38%) and progressive disease (PD) in seven (17%). Six of 19 patients (32%) who achieved objective responses (ORs) underwent surgery. The median time to failure and median survival time have not been reached yet. There were no therapy-related deaths. The dose-limiting toxicity was myelosuppression. Leukopenia occurred in 35 patients (81%) and was grade 3 or 4 in seven (17%). Twelve patients (28%) developed peripheral neuropathy, while myalgias occurred in 10 (23%). Constipation was observed in nine patients (21%), one with a prolonged ileum. Phlebitis was recorded in 18 patients (41%). In contrast, emesis and mucositis were rarely observed. No patient developed alopecia grade 3. By the end of the twelfth course of treatment, the average received dose-intensity was 85.4% of that projected. CONCLUSION: VNB is an active drug against ACC with moderate toxicity. Its activity is among the highest reported for single agents. Further evaluation in association with other agents is clearly justified.     

Prognostic factors and treatment of advanced Hodgkin's disease

Treatment strategy is based on prognosis groups although there is no consensus on their definition. In stages IIIA with unfavorable factors and stages IIIB or IV without high risk factors, chemotherapy alone or followed by irradiation is used. To reduce toxicity, radiation therapy on bulky disease and residual masses is preferred to extended fields. Indications for intensive chemotherapy with autograft of hematopoietic stem cells as initial treatment for high-risk patients must be determined with therapeutic trials.     

Prognostic significance of DNA flow cytometric analysis in patients with nasopharyngeal carcinoma

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a prevalent malignant tumor among Southern Chinese. Previously, the authors described the prognostic significance of a serum antibody assay to a recombinant Epstein-Barr virus Bam HI-Z replication activator protein (ZEBRA) in NPC patients with long term follow-up. In this study, the authors further reported the use of DNA flow cytometry (DNA-FCM) as an additional technique for determining the prognosis of NPC patients in the same series. METHODS: One hundred and forty-three archival biopsies from 110 NPC patients were deparaffinized and subjected to DNA-FCM analysis. DNA ploidy state and various proliferative indices (PI) of the tumors were correlated with patient survival and frequency of recurrence. RESULTS: Among the biopsies analyzed, 119 were histologically positive NPC and 24 were negative. Fifty-one tumor biopsies that fulfilled the guideline criteria of the DNA Cytometry Consensus Conference were correlated with the clinical manifestations of the patients. Among them, 43 tumors (84%) were DNA diploid and 8 (16%) were aneuploid. Two PI, S-phase fraction (SPF) and proliferation fraction (PF), appear to be potentially useful prognostic indicators. For example, PF in patients who developed locoregional recurrence (15.1%) and distant recurrence (16.4%) after radiation therapy both were significantly higher than PF in patients who were in complete remission (8.2%) (P = 0.0005 and P = 0.004, respectively). Significant differences in SPF between patients with distant recurrence (10.6%) and those in remission (5.7%) also was found (P = 0.005). Using Kaplan-Meier analysis, patients with high PF, high SPF, and aneuploid tumors had significantly poorer 12-year survival rates (35%, 26%, and 28%, respectively) than those patients with low PF, low SPF, and diploid tumors (77%, 67%, and 59%, respectively) (P < 0.0009, P < 0.004, and P < 0.01, respectively). CONCLUSIONS: Determination of tumor PI and DNA ploidy state by DNA-FCM at diagnosis of NPC can be potentially useful in selecting a poor prognostic subgroup of NPC patients. These parameters may enable oncologists to plan for more stringent treatment strategies such as hyperfractionated and accelerated radiation therapy or concomitant chemoradiotherapy for these patients.