Outpatient weekly neoadjuvant chemotherapy followed by radiotherapy for advanced nasopharyngeal carcinoma: high complete response and low toxicity rates.

Nasopharyngeal carcinoma (NPC) is a radiosensitive and chemosensitive tumour. The aim of this prospective study is to evaluate the toxicity and efficacy of an outpatient weekly neoadjuvant chemotherapy (NeoCT) plus radiotherapy for advanced NPC. From November 1998 to August 2001, 90 NPC patients meeting the following criteria were treated: (1) neck node >6 cm; (2) supraclavicular node metastasis; (3) skull base destruction/intracranial invasion plus multiple nodes metastasis; (4) multiple neck nodes metastasis with one of nodal size >4 cm; or (5) elevated serum LDH level. The NeoCT consists of cisplatin 60 mg m(-2), alternating with 5-fluorouracil 2500 mg m(-2) plus leucovorin 250 mg m(-2) (P-FL) by an outpatient weekly schedule for a total of 10 weeks. Local radiotherapy > or =70 Gy by conventional fractionation was delivered within 1 week after NeoCT. Patient compliance was rather good. Grade 3-4 toxicity of NeoCT included leucopaenia (7.8%), anaemia (18.9%), thrombocytopaenia (3.3%), nausea/vomiting (4.4%), and weight loss (1.1%). Response evaluated after NeoCT showed 73.3% complete response (CR) rate of primary tumour, 71.1% CR rate of neck nodes, and an overall CR rate of 57.8%. In all, 88 out of 90 patients received rebiopsy of primary tumour and 55 patients (62.5%) revealed pathological CR. After a median follow-up time of 24 months, one persistent disease and 18 relapses were noted. The 2-year nasopharynx disease-free, neck disease-free, distant disease-free, overall, and progression-free survival rates are 98.9, 95.9, 80.0, 92.1, and 77.5%, respectively. Preliminary data of the current study show that P-FL NeoCT plus radiotherapy is a low-toxic regimen with promising results on very advanced NPC patients and merits to be investigated in phase III trials.

Detection of Epstein-Barr virus DNA in the peripheral-blood cells of patients with nasopharyngeal carcinoma: relationship to distant metastasis and survival.

PURPOSE: Nasopharyngeal carcinoma (NPC) has been proved to be an Epstein-Barr virus (EBV)-associated cancer. By use of nested polymerase chain reactions (PCRs), we examined whether the presence of EBV DNA in the peripheral-blood cells (PBC) can serve as a prognostic indicator for NPC. PATIENTS AND METHODS: Peripheral blood from 124 patients with NPC who had no evidence of distant metastasis and 114 healthy volunteers with serologically positive findings for EBV infection was collected prospectively. Plasma and erythrocytes were separated. DNA was extracted from PBCs and analyzed by a nested PCR using primers specific to Epstein-Barr virus nuclear antigen 1 (EBNA-1). All patients were treated by radiotherapy with or without chemotherapy. Clinical parameters and status of EBNA-1 in PBCs were used for survival analysis using the Kaplan-Meier method and the Cox proportional hazards model. RESULTS: Positive rates of EBNA-1 DNA in PBCs of NPC patients and healthy volunteers are 71% and 14%, respectively (P =.001). No significant difference was observed with regard to the clinical characteristics of patients who were EBNA-1-positive (n = 88) and those who were EBNA-1-negative (n = 36). After a median follow-up period of 38 months (range, 24 to 56 months), 29 of 88 EBNA-1-positive patients and only one of 36 EBNA-1-negative patients developed distant metastases (P =.00015). Kaplan-Meier estimates of overall survival (P =.0010), metastasis-free survival (P =.0004), and progression-free survival (P =.0004) were significantly lower for the patients in the EBNA-1-positive group than for those in the EBNA-1-negative group. Multivariate Cox analysis confirmed the same results. CONCLUSION: The presence of EBNA-1 DNA in PBCs is a novel, important risk factor for patients with NPC that indicates a significantly higher risk of developing distant metastasis as well as a lower survival rate.

Detection of circulating tumor cells in venous blood of nasopharyngeal carcinoma patients by nested reverse transcriptase-polymerase chain reaction.

Nasopharyngeal carcinoma (NPC) is a radiosensitive tumor. Because of recent advances in radiation oncology, distant metastasis has become the predominant failure site after adequate radiotherapy. The purpose of this study is to establish a nested reverse transcriptase-polymerase chain reaction (RT-PCR) system and to evaluate the potential of cytokeratin 19 (CK-19) mRNA as a target for detecting micrometastasis in the blood of NPC patients. Venous blood samples from 40 patients with biopsy-proven NPC (25 previously untreated and 15 after radiotherapy) and 20 healthy volunteers were tested. We divided the 40 patients into 4 groups: cured, early stage, advanced stage, and metastasized, according to results of clinical staging work-up. Under our nested RT-PCR experimental conditions, 2 of 8 early stage patients (25.0%), 6 of 15 advanced stage patients (40%), and 6 of 8 patients with distant metastasis (75%) had CK-19 positive cells in peripheral blood (P = 0.11). No CK-19 positive cells were detected in 9 "cured" patients and 20 healthy volunteers. Our data indicated that the positive detection rate for CK-19 mRNA in peripheral blood increased as the clinical stage of disease increased, but the difference did not reach statistical significance. Longer follow-up is needed to assess the significance of CK-19 mRNA in blood, as well as its relation to subsequent metastasis and prognosis of NPC.

Locally advanced nasopharyngeal cancer: long-term outcomes of radiation therapy.

PURPOSE: To investigate the clinical manifestations and treatment outcomes in patients with stage T4M0 nasopharyngeal carcinoma. MATERIALS AND METHODS: Findings in 179 patients (age range, 13-78 years) with American Joint Committee on Cancer stage T4M0 nasopharyngeal carcinoma treated from January 1983 to February 1992 with a minimum follow-up of at least 5 years were reviewed. Of the 179 patients, 166 (92.7%) had World Health Organization type II or III disease. Forty-one patients (22.9%) had no lymph nodal involvement; 138 patients (77.1%) had metastatic nodal involvement in the neck. All patients underwent radiation therapy; 39 patients also received different forms of chemotherapy. The radiation therapy doses were usually 70-74 Gy administered to the primary tumor over 7 or 8 weeks, 70-74 Gy to the neck region in patients with nodal involvement, or 50-60 Gy administered to the neck region over 5 or 6 weeks in patients without neck nodal involvement. RESULTS: In 100 patients, radiation therapy failed in the primary tumor alone (n = 28), neck nodes alone (n = 5), and distant metastases alone (n = 43) or at a combination of sites (n = 24). The cumulative failure rates for the primary tumor, neck metastases, and distant metastases were 25.1% (n = 45), 14.0% (n = 25), and 33.0% (n = 59), respectively. The 5-year primary disease-free, distant disease-free, and overall survival rates were 68.7%, 56.5%, and 28.6%, respectively. Results of salvage treatment for relapse were unsatisfactory. CONCLUSION: In about three-tenths of patients, T4M0 nasopharyngeal carcinoma can be cured with conventional high-dose radiation therapy.

High rate of clinical complete response to weekly outpatient neoadjuvant chemotherapy in oral carcinoma patients using a new regimen of cisplatin, 5-fluorouracil, and bleomycin alternating with methotrexate and epirubicin.

BACKGROUND: A Phase II trial was initiated to evaluate the response to and toxicity of a new regimen of weekly outpatient neoadjuvant chemotherapy in patients with oral carcinoma. METHODS: Patients with previously untreated squamous cell carcinoma of the oral cavity were eligible for this trial. The neoadjuvant chemotherapy was comprised of cisplatin, 25 mg/m2, 5-fluorouracil, 1000 mg/m2, and bleomycin, 10 mg/m2, mixed in normal saline as a 24-hour intravenous (i.v.) infusion, alternating with methotrexate, 30 mg/m2, and epirubicin, 30 mg/m2, as an i.v. bolus (PFB/ME) on a weekly schedule for 8-12 weeks. In patients with American Joint Committee on Cancer Stage IV disease who completed neoadjuvant chemotherapy, surgery was preferred to radiotherapy, unless patients refused surgery. RESULTS: A total of 40 patients (82.5% with Stage IV disease) with previously untreated oral carcinoma were enrolled. The median size of the primary tumor was 7 cm (range, 3-13 cm). Fifty percent of patients had tumor penetrating through the oral mucosa to the cheek skin and 62.5% had bony destruction. Detectable cervical lymph nodes were noted in 77.5% of patients. After neoadjuvant weekly chemotherapy, 22 patients (55%) showed complete response (CR) and 15 patients (37.5%) showed partial response, for an overall response rate of 92.5%. World Health Organization Grade 3/4 toxicity included mucositis (7.5%), leukopenia (25%), anemia (10%), and thrombocytopenia (2.5%). Eleven of 33 patients with Stage IV disease underwent surgery, and pathologic CR (2 patients) or microscopic residual tumor (4 patients) was noted (54.5%). CONCLUSIONS: The results of the current study indicate that a weekly PFB/ME neoadjuvant chemotherapy regimen is highly effective for the treatment of patients with oral carcinoma. In addition, this regimen has low toxicity. The authors believe that implementation of this regimen into a multimodality therapy protocol deserves further study.

Outpatient weekly chemotherapy in patients with nasopharyngeal carcinoma and distant metastasis.

BACKGROUND: Distant metastasis is a more common pattern of failure than locoregional recurrence after adequate radiotherapy in patients with nasopharyngeal carcinoma (NPC). The objective of this Phase II study was to assess the efficacy and toxicity of weekly chemotherapy in NPC patients with distant metastasis. METHODS: Patients with a histologic diagnosis of NPC and documented distant metastasis were eligible, including those who 1) had metastatic disease at presentation; 2) had developed metastatic disease during or at any time after local radiotherapy; or 3) had developed progressive disease or recurrence of metastasis after prior chemotherapy. The weekly chemotherapy regimen was comprised of 5-fluorouracil (5-FU), 1250 mg/m2, plus cisplatin, 25 mg/m2, as a 24-hour continuous intravenous infusion via a subcutaneous implanted port, using an ambulatory pump in an outpatient setting for the first 19 patients. Because of the low incidence and reduced severity of toxicity, the dosage of chemotherapy was escalated to 5-FU, 1667 mg/m2, plus cisplatin, 33.3 mg/m2, for the subsequent 25 patients. RESULTS: Between October 1992 and June 1996, a total of 44 patients with metastatic NPC were studied. They were 36 males and 8 females with a median age of 48 years (range, 30-72 years). Poorly differentiated epidermoid carcinoma or undifferentiated carcinoma were the major pathologic types. Twenty-six patients had single organ metastasis, whereas 18 patients had multiple organ involvement. Locoregional disease existed simultaneously in 16 patients. The majority of patients had received previous radiotherapy (33 patients) and chemotherapy (23 patients: 16 as concurrent therapy for localized disease, 6 as salvage therapy for metastatic disease, and 1 for a postradiation adjuvant purpose). Among 38 patients with measurable disease, 8 obtained a complete response (CR) (21.1%), 12 obtained a partial response (PR) (31.6%), 17 had stable disease (SD) (44.7%), and 1 had progressive disease (2.6%). The median duration of CR, PR, and SD were 6.5 months, (range, 2-12 months), 5.5 months (range, 2-9 months), and 2.5 months (range, 1-6 months), respectively. Toxicity was found to be very mild. Only one patient developed a World Health Organization (WHO) Grade 1 mucositis. No visible alopecia and no treatment-related deaths occurred. WHO Grade 3-4 hematologic toxicities occurred in 1.0% of patients for leukopenia, 4.1% for anemia, and 2.9% for thrombocytopenia. CONCLUSIONS: Data from the current study indicate that 24-hour weekly infusion of 5-FU plus cisplatin has moderate activity but very low toxicity for NPC patients with distant metastasis. Further study is necessary to find more effective therapy.

Polyethylene failure in New Jersey low-contact stress total knee arthroplasty.

From January 1985 to December 1990, 598 consecutive New Jersey low-contact stress (LCS) total knee arthroplasties (TKAs) were performed for gonarthrosis. Among these 598 operations, 322 were with rotating platform elements and 276 were with meniscal bearing elements. During 5 to 8 years of follow-up, eight knees had severe symptomatic polyethylene failure that required revision surgery; all eight cases were meniscal bearing types. The failed polyethylene inserts were retrieved and studied. It was observed that there were four probable failure mechanisms associated with the catastrophic polyethylene wear. First, insufficient thickness of the meniscal bearing was the major reason for wear. Second, the malpositioning of the metal tibial tray in the transverse plane resulted in the breaking of the meniscal bearing. Third, the inability of the patellar to rotate due to tissue ingrowth made the polyethylene break. Last, yellowing of the subsurface of the meniscal bearing was a sign of polyethylene failure. These four possible failure mechanisms are all associated with the design of the meniscal bearing type of LCS knee prostheses. Therefore, it is suggested that the design of the LCS knee prosthesis should be modified.

Measurement of the radiation doses absorbed by jaw bones during irradiation of nasopharyngeal cancers.

BACKGROUND: Nasopharyngeal carcinoma (NPC) occurs more frequently for Chinese than for other ethnic groups. The most common treatment for NPC is radiotherapy, but there is no report of the doses of radiation absorbed by the mandibular and maxillary bones, although exposure to radiation is one of the most important references for those patients who need to have oral surgical treatments. METHODS: Thermoluminescent dosimeter (TLD) was used to measure radiation absorbed by a rando phantom and cancer patients. RESULTS: The results showed that the doses absorbed by the mandible and maxilla depend on the dose applied, field size, and field shape. In the rando phantom, the range of absorption in the mandible was, for the central incisor 1.89-3.36 Gy, canine 1.96-3.78 Gy, bicuspid 2.24-14.14 Gy, second molar 4.34-31.92 Gy, internal pterygoid muscle region 70 Gy. In the maxilla the range was, for the central incisor 2.17-2.94 Gy, canine 2.24-3.36 Gy, bicuspid 3.15-4.41 Gy, second molar 7.00-7.42 Gy. In nasopharyngeal carcinoma patients, the mean radiation absorbed by the bicuspid vestibular region of the mandible was 3.09 Gy, by the bicuspid vestibule of the maxilla 3.35 Gy and by the midline vestibule 2.31 Gy. The radiation doses absorbed by maxilla and mandible from the incisor to the second premolars were less than 20% of the dose to the primary tumor. CONCLUSIONS: The doses absorbed by the mandible and maxilla are relatively low in NPC patients receiving radiation therapy.

Pilot study of concurrent chemotherapy and radiotherapy for stage IV nasopharyngeal cancer.

Nasopharyngeal carcinoma (NPC) is a more radio- and chemosensitive tumor than all other head and neck cancers. Between September 1991 and December 1992, a total of 19 patients (13 men and six women; median age, 44 years) with AJCC stage IV NPC were entered into a pilot study of concurrent chemoradiotherapy. Pathology showed either poorly differentiated epidermoid carcinoma or undifferentiated carcinoma. Radiotherapy was delivered using a telecobalt unit and 10-MV x-rays and by conventional fractionation (1.8-2.0 Gy/fraction, 5 fractions/week). The total doses delivered were 70-75 Gy to the primary tumor and neck positive region, and 50-55 Gy to the neck negative area. Chemotherapy with cisplatin (10 mg/m2/day, days 1-5) and 5-fluorouracil (500 mg/m2/day, continuously infused for 5 days) was administered concurrently during weeks 1 and 5 of radiotherapy. The major toxicities were mucositis (42% had grade III and 58% grade II) and leukopenia (nadir white blood cells <3,000/mm3 in eight of 19). Although four patients required a delay in their second cycle of concurrent chemotherapy or had their radiotherapy interrupted for 1 week, all 19 patients completed the planned treatment and achieved a 100% complete response rate. After a median follow-up period of 42 months, one patient suffered from neck recurrence plus distant metastasis, and three patients developed distant metastases alone. The 3-year overall and disease-free survival rates are 89.5% and 83.3%, respectively. Our data indicated that concurrent chemoradiotherapy for advanced NPC is both feasible and effective, with acceptable toxicities. A phase III randomized trial to compare the efficacy of concurrent chemoradiotherapy and radiotherapy alone deserves to be studied further.

Partially hyperfractionated accelerated radiotherapy and concurrent chemotherapy for advanced nasopharyngeal carcinoma.

PURPOSE: A newly designed concomitant chemoradiotherapy was undertaken to assess the feasibility and efficacy for advanced nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: Sixty-three patients with biopsy-proven NPC were entered in this Phase II trial from March 1992 to November 1993. Most patients present with Stage IV disease (93.4%) and poorly differentiated epidermoid carcinoma or undifferentiated carcinoma were the major pathologic type. Radiotherapy was delivered using a telecobalt unit and 10 MV x-rays and by altered fractionation (72-74 Gy/45 fractions/6 weeks). Chemotherapy with cisplatin 75 mg/m2, 2 h infusion at day 1, followed by 5-FU 400 mg/m2/day, continously infused for 4 days was given concurrently during the first and fifth weeks of radiotherapy. RESULTS: The major toxicity was mucositis (61% belong to Grade 3, 31% to Grade 2). Weight loss, leucopenia, and skin reaction were frequently encountered. Three patients withdrew from treatment at 15, 25, and 55.5 Gy, three patients interrupted the radiotherapy for 1-4.5 weeks, and two patients refused the second cycle of concomitant chemotherapy due to toxicities. The initial tumor response showed 100% overall response rate, with 90.5% complete response. After a median follow-up time of 38 months, five patients failed at the primary and/or neck (four recurrent and one persistent), and 14 patients developed distant metastases alone. The 3-year primary disease-free, regional disease-free, distant disease-free, and overall survival rates are 89.1, 92.8, 74.3, and 73.6%, respectively. The late complication rate is acceptable so far. CONCLUSIONS: Our data indicates that concurrent chemoradiotherapy for advanced NPC is both feasible and effective, with acceptable toxicities. Distant metastases are the major site of treatment failure. Postradiation adjuvant chemotherapy to eradicate subclinical distant metastasis should be further studied.

Preliminary report of outpatient weekly adjuvant chemotherapy for high-risk nasopharyngeal carcinoma.

Distant metastasis has become the most frequent failure site-more so than locoregional relapse-after adequate radiotherapy in nasopharyngeal carcinoma (NPC). A prospective study was initiated to test the role of postradiation adjuvant chemotherapy using a weekly schedule for selected patients with high-risk NPC (N3, T4N2b-2c, and N2b-2c, with one of nodal size > 4 cm, or residual disease after radiotherapy). Through July 1993 to August 1994, a total of 20 patients were entered into the study: 16 men and four women, with a median age of 49 years and age range of 27-75 years. Pathology showed WHO type I:II:III = 2:13:5. Previous treatment consisted of concurrent chemoradiotherapy (16 patients), radiotherapy alone (two), and neoadjuvant chemotherapy followed by radiotherapy (two). Postradiation adjuvant chemotherapy was usually started 2 months after radiotherapy, using a weekly FP schedule (5-fluorouracil 1,250 mg/m2 + cisplatin 25 mg/m2, mixed in 100 ml saline, 24 h continuous i.v. infusion) for 18 weeks. The treatment of five patients was at 5, 6, 10, 14, and 15 weeks because of leukopenia-induced mortality, sudden death unrelated to adjuvant chemotherapy, a patient's refusal, and distant metastasis (the last two cases) during adjuvant chemotherapy. The major toxicity was leukopenia (grade I, 20%; grade II, 45%; grade III, 15%; and grade IV, 10%). Ten patients (50%) developed distant metastasis after a median follow-up time of 20 months. Our preliminary data indicate that postradiation adjuvant chemotherapy with a weekly FP regimen at our dosage is not recommended for high-risk NPC.

Malignant soft tissue sarcoma of the hypopharynx successfully treated by radiotherapy alone.

Sarcoma of the hypopharynx has been reported very rarely in the literature, only six cases having been found among all head and neck malignancies reported to SEER (Surveillance, Epidemiology, and End Results) during 1973-1987. We report a 14-year-old boy with a huge malignant soft tissue sarcoma arising from the hypopharynx. Tracheostomy and feeding gastrostomy were performed as emergency life-saving procedures. Surgical resection had been attempted, but abandoned. Because of the rapidity of tumor growth, we gave the patient a course of accelerated radiotherapy (170 cGy/fraction, two fractions per day) with a total dose of 7140 cGy within one month. A series of endoscopy and imaging studies demonstrated complete regression of the tumor, and the patient is currently alive without evidence of disease 3.5 years after treatment. We conclude that for an unresectable tumor without distant metastasis, radiation therapy may be tried. The time, dose, and fractionation of radiotherapy should be carefully designed and individualized.

High complete response rate of concomitant chemoradiotherapy for locally advanced squamous cell carcinoma of the uterine cervix.

A prospective study with a newly designed schedule of concomitant chemoradiotherapy was initiated for 42 patients with previously untreated squamous cell carcinoma of the uterine cervix. Their ages ranged from 34 to 77 years, median 57 years. There were 13 FIGO stage IIB, 1 IIIA, 27 IIIB, and 1 IVA. Radiotherapy was administered using 1.8 Gy/day, 5 days a week, to the whole pelvis (50.4 Gy/28 fractions) with local boost if indicated. Intracavitary brachytherapy of 5 Gy for five times was delivered after 1-2 weeks of rest. The first 21 patients received concomitant chemotherapy of biweekly PEB regimen (100 mg/m2 etoposide + 50 mg/m2 cisplatin + 50 mg/m2 bleomycin) for two to three cycles during external irradiation. The chemotherapy for the latter 21 patients was modified to weekly PEBF (50 mg/m2 etoposide + 20 mg/m2 cisplatin + 10 mg/m2 bleomycin + 800 mg/m2 5-FU, mixed in normal saline, 24-hr continuous iv infusion) for five to six cycles. All except 1 patient achieved complete response (97.6%) and sustain so after a median follow-up time of 30 months. There were three relapses--one with persistent pelvic disease and two with distant metastasis. Two-year overall survival and disease-free survival rates were 97.6 and 92.9%, respectively. Myelosuppression was moderate but fully recovered. Other acute toxicities were tolerated except for 1 patient who encountered grade IV radiation colitis with cecum perforation and required surgery. As to late morbidity, the incidence of radiation proctitis was high (21.4%) but of a mild degree, with 1 patient needing repeated transfusion. One patient developed chronic cystitis with an acontractile bladder. Our preliminary results show that concomitant chemoradiotherapy for advanced cervical carcinoma is both feasible and effective with acceptable toxicities. Further follow-up is mandatory to ensure whether this high complete response protocol will translate into long-term local control and survival.

Comparison of TI-201 and Tc-99m MIBI SPECT imaging in nasopharyngeal carcinoma.

Both TI-201 and Tc-99m MIBI uptake in nasopharyngeal carcinoma (NPC) have been reported, yet no comparative study of these two agents using SPECT images has been undertaken for NPC. This study compares the relative effectiveness of TI-201 and Tc-99m MIBI SPECT for detecting NPC. In the patients with NPC, 26 of 32 (81%) showed TI-201 tumor uptake, whereas 24 of 32 (75%) showed Tc-99m MIBI tumor uptake. This preliminary study suggests that both Tc-99m MIBI and TI-201 SPECT imaging can be helpful in detecting NPC, and that sensitivity is slightly higher in TI-201 SPECT imaging.

Somatosensory evoked potential study in cervical radiation myelopathy.

BACKGROUND: To correlate the findings of median nerves somatosensory evoked potentials (SEPs) with clinical manifestations and magnetic resonance (MR) findings in cervical radiation myelopathy after therapeutic irradiation for nasopharyngeal carcinoma. METHODS: Median nerve somatosensory evoked potentials (SEPs) were recorded in 10 patients with cervical radiation myelopathy. Seven patients were studied by SEP once, two patients received SEP twice, and one patient, three times. RESULTS: On the basis of the median nerve SEP findings, three groups were identified: Group I, normal SEP responses (N9, N13 and N20); Group II, normal N13 with abnormal N20; Group III, Normal or abnormal N9 with both abnormal N13 and N20. CONCLUSIONS: The size, eccentricity and extension to the dorsal columns of the lesions correlated well with SEP findings. When the lesions were confined mainly to the lateral column without much involvement of the dorsal columns, SEP findings were normal; with more extensive lesions involving the dorsal columns, SEPs became abnormal.

Serial MRI changes in radiation myelopathy.

Using MRI we assessed the changes in signal, size, and contrast enhancement characteristics of the cervical spinal cord in radiation myelopathy developing after radiotherapy for nasopharyngeal carcinoma. We studied two men and five women, aged 40-77 years. The first MRI study was performed 1-4 months after the initial clinical manifestations of myelopathy, and follow-up MRI 2-22 months after the onset of symptoms. On the first study, all patients showed low signal intensity in a long segment of the cervical spinal cord on T1-weighted images, high signal on T2*-weighted images, and focal contrast enhancement at C1-2. In five patients there was also swelling of the spinal cord. The site of eccentric focal contrast enhancement correlated with the clinical manifestations. Follow-up imaging less than 10 months after the onset of symptoms showed no significant changes in signal intensity. Focal contrast enhancement at C1-2 remained the same in three patients, was more dense and larger in one, and less dense in another. Subsidence of swelling was seen in two patients. Atrophy of the spinal cord at C1-2, without abnormal signal and with faint contrast enhancement at C1-2 was revealed as early as 10 months after the onset of symptoms, but the contrast enhancement disappeared by 22 months. There was no correlation between clinical manifestations and spinal cord atrophy on MRI.

Neoadjuvant chemotherapy for advanced nasopharyngeal carcinoma.

Between October 1990 and November 1991, a total of 16 male patients with advanced nasopharyngeal carcinoma were treated by neoadjuvant chemotherapy before conventional radiotherapy. They belonged to the AJCC stage IV with multiple bulky neck nodes metastases. The chemotherapy consisted of bleomycin, epirubicin, and cisplatin. Six patients completed 3 cycles, 9 patients finished 2 cycles, and 1 patient received 1 cycle of chemotherapy. Seven of the 16 patients (44%) were in complete response, and 50% (8/16) achieved partial response. The overall response rate was 94%. The major toxicities consisted of leucopenia (12/37 cycles had grade III-IV), nausea/vomiting, alopecia. Aplastic marrow developed in 1 patient, and one died of bleomycin-induced pneumonitis. Subsequent radiation therapy was well tolerated. After a minimal follow-up time of 24 months, the 2-year actuarial survival rate was 56%. Although we confirmed the impressively high response rate of this regimen, the toxicities were high and most patients failed at distant site(s). The efficacy of neoadjuvant chemotherapy for advanced nasopharyngeal carcinoma is doubtful and should be further studied in prospective randomized trials.

Concomitant chemoradiotherapy for advanced epidermoid carcinoma of the uterine cervix: a preliminary report.

BACKGROUND: Because the prognosis of advanced carcinoma of the uterine cervix is poor, and has improved very little in the last 20 years, a prospective study was initiated to evaluate the feasibility, response and toxicities of concomitant chemoradiotherapy for such cervical cancer. METHODS: From May 1992 to December 1992, 22 patients entered the study, 21 of them completed the entire treatment. Their ages ranged from 47 to 72 years, median 57. There were 16 FIGO stage IIIB, and 5 stage IIB. Radiotherapy was administered using 1.8 Gy/day, five days a week, to the whole pelvis (50.4 Gy/28 fractions) with or without parametrial boost according to the tumor response. Intracavitary brachytherapy 5 Gy x five to six times was given after one or two weeks of rest. Chemotherapy consisted of etoposide 100 mg/m2 day 1 + cisplatin 50 mg/m2 day 1 + bleomycin 25 mg/m2/day day 2-3, repeated every two weeks during external irradiation. RESULTS: All 21 eligible patients achieved complete response, sustaining during a median follow-up time of 12 months. All the initially elevated tumor markers (SCC, CEA, CA-125) returned to normal range after treatment. The toxicity was well tolerated. CONCLUSIONS: Concomitant chemoradiotherapy for advanced cervical carcinoma is both feasible and effective, with acceptable toxicities. Long-term follow-up is mandatory, and a randomized trial to confirm the superiority of this protocol will be started soon.

Concomitant chemoradiotherapy for advanced head and neck cancer.

Head and neck cancer is mostly curable in the early stages by either surgery or radiotherapy alone, but the control rate for advanced stages is low, even with combined surgery and postoperative radiotherapy. From September, 1990, to January, 1992, 35 patients with locoregionally advanced head and neck cancers were entered in a prospective study of concomitant chemoradiotherapy. Thirty-three completed the treatment. There were 29 males and four females with a median age of 53 years. All except one patient were in stage IV. Radiotherapy was delivered using a telecobalt unit and by conventional fractionation (1.8 Gy/fraction, 5 fractions/wk). Chemotherapy with cisplatin (10 mg/m2/day, daily, days 1-5) and 5-FU (500 mg/m2/day continuously infused for five days) was given concurrently during the first and fifth weeks of radiation. Twenty-four among 31 eligible patients achieved complete response (77.4%) and the other seven (22.6%) partial response, resulting in a 100% response rate. The toxicities experienced were increased compared with those caused by radiotherapy alone. The most common side effects were gastrointestinal and hematologic toxicities but the whole treatment was well tolerated. The two-year actuarial survival rate is 45%. We found the primary origin and overall treatment time to affect survival significantly. The survival rate for tumors arising from the nasopharynx or paranasal sinus is better than for those arising from other regions of the head and neck. The shorter treatment times (within eight weeks) had a better survival rate. Our preliminary experience suggests that concomitant chemoradiotherapy is both feasible and effective for head and neck cancer. The optimal scheduling and dosage of concomitant chemoradiotherapy should be further researched.