Chemotherapy for cervical carcinoma: factors determining response and implications for clinical trial design

PURPOSE: To identify characteristics that predict response to chemotherapy in patients with advanced or recurrent squamous cell carcinoma of the cervix. PATIENTS AND METHODS: Between January 1986 and May 1996, 190 chemotherapy-naive patients with advanced or recurrent squamous cell carcinoma of the cervix not amenable to curative radiation therapy or surgery were treated on 14 different chemotherapy protocols at M.D. Anderson Cancer Center. Patient's charts were retrospectively reviewed for patient demographics, tumor and treatment characteristics, and patterns of response and survival. RESULTS: Of 190 patients, 22 had advanced or persistent disease and 168 had recurrent disease. Patients were treated with platinum-based (n=95) and non-platinum-based (n=95) regimens. The overall response rate was 20.0% (4.2% complete response; 15.8% partial response), with a median response duration of 4.8 months. Race, socioeconomic class, tumor stage and grade, mode of primary treatment, time from primary diagnosis to disease recurrence, initial performance status, and use of platinum-based therapy were not significant predictors of response. Age at time of chemotherapy (P=.001) and site of recurrence (P=.044) were significant determinants by multivariate analysis. Patients who were older were more likely to respond to therapy, and the response rate for patients in whom disease recurred outside the irradiated field was 25.2%, compared with a 5.3% response rate for patients with recurrent disease limited to a previously irradiated field. CONCLUSION: The site of disease recurrence and patient age should be taken into account when designing chemotherapy trials and also when considering chemotherapy in the patient with recurrent cervix cancer.     

Salvage therapy for ovarian cancer

Patients with epithelial ovarian cancer must receive optimal surgical care and state-of-the-art chemotherapy in the primary treatment setting. The salvage treatment of women with recurrent or persistent ovarian cancer remains a difficult task. A very small percentage of patients with platinum-sensitive, small-volume disease appear to achieve prolonged disease-free survival. The treatment of patients with larger-volume disease (> 0.5 cm) or platinum-resistant disease remains largely palliative. The plethora of available new agents has provided the physician with multiple options for salvage chemotherapy. Although cure in the salvage setting is not often achieved currently, palliative treatment allows many patients to live painfree, productive lives. Candidates for salvage therapy may be grouped into one of several categories, which reflect different prognoses for response. These categories include refractory disease (defined as progressive tumor during primary treatment), persistent disease (a partial response to primary therapy followed by elevated tumor markers or clinically evident persistent disease), and recurrent disease (initial complete response to primary therapy with subsequent relapse). Categorizing patients into these categories provides a systematic method for organizing the administration of salvage chemotherapy.     

Results of salvage abdominoperineal resection for anal cancer after radiotherapy

PURPOSE: Nonsurgical treatment of anal cancer by radiotherapy alone or combined with chemotherapy is the standard therapy for epidermoid carcinoma of the anal canal. Surgery is only recommended for treatment failures. Very few studies have been devoted to the outcome of this salvage surgery. The aim of this study is to evaluate these results. METHODS: A retrospective review from 1986 to 1995 revealed 21 patients with residual or recurrent anal canal carcinoma after initial radiotherapy, operated on by abdominoperineal resection. Patients were reviewed as to age, gender, initial treatment, any symptoms of recurrence, duration until recurrence, any diagnosis imaging, treatment, and outcome. RESULTS: None of these 21 patients had known lymph node involvement or metastases at radiotherapy or at salvage abdominoperineal resection. Eleven patients had residual disease (positive biopsy less than 6 months after the end of radiotherapy) and 10 had tumor recurrence (more than 6 months after cessation of treatment). Recurrence occurred at a mean of 15 (range, 9-41) months after radiotherapy. All 21 patients underwent an abdominoperineal resection. Pathologic examination of the 21 specimens showed complete excision in all cases except one and lymph node metastases in two cases. There was no perioperative mortality. The mean follow-up after surgery was 40 months; no patients were lost to follow-up. Of the 21 patients, 10 died and 11 lived, of whom 9 are disease free. The overall survival rate at three years after salvage abdominoperineal resection was 58 percent. The overall survival rate for patients with residual disease (vs. recurrence) at three years was 72 percent (vs. 29 percent) and at five years was 60 percent (vs. 0 percent; P = 0.06). CONCLUSIONS: Salvage abdominoperineal resection for anal cancer can be expected to yield a number of survivors from residual disease, but the low rate of survival after abdominoperineal resection for recurrent disease suggests the need for additional postoperative treatment if salvage abdominoperineal resection is performed.     

Induction cisplatin/vinblastine and irradiation vs. irradiation in unresectable squamous cell lung cancer: failure patterns by cell type in RTOG 88-08/ECOG 4588. Radiation Therapy Oncology Group. Eastern Cooperative Oncology Group

PURPOSE: To analyze disease failure patterns by pretreatment characteristics and treatment groups in a prospective randomized trial. METHODS AND MATERIALS: Patients with medically inoperable Stage II, unresectable IIIA and IIIB nonsmall cell lung cancer with KPS > or =70 and weight loss < or =5% were randomized to one of three treatment groups: standard radiation therapy with 60 Gy at 2.0 Gy per day (STD RT), induction chemotherapy with cisplatin 100 mg/m2 days 1 and 29 with vinblastine 5 mg/m2 weekly for 5 weeks followed by 60 Gy at 2.0 Gy per day (CT + RT), or hyperfractionated radiation therapy with 69.6 Gy at 1.2 Gy b.i.d. (HFX RT). Of 490 patients enrolled, 458 were evaluable. Minimum and median periods of observation for this analysis were 4 years and 6 years, respectively. RESULTS: Pretreatment characteristics were equally distributed. Toxicities were previously reported. Median survival rates were 11.4, 13.6, and 12.3 months for STD RT, CT + RT, and HFX RT, respectively (log rank p = 0.05, Wilcoxon p = 0.04). Survivals were 20, 31, and 24% at 2 years, and 4, 11, and 9% at 4 years in the STD RT, CT + RT, and HFX RT groups, respectively. There were no differences in local tumor control rates among the treatments. Patterns of first failure showed less distant metastasis (DM) (other than brain) for CT + RT compared to the RT alone arms (p = 0.04). Within squamous cell carcinoma (SCC), DM (other than brain) rates were 43%, 16%, and 38% in SCC for STD RT, CT + RT, and HFX RT, respectively (p = 0.0015). Patients with peripheral/chest wall lesions were significantly more likely to fail first in the thorax when treated on STD RT compared to CT + RT and HFX RT (p = 0.009). Survival rates were similar among the treatment arms for patients with squamous cell carcinoma. Among patients with nonsquamous cell carcinoma, failure patterns did not differ by treatment group, but survival was significantly better in those who were treated by induction chemotherapy (p = 0.04). CONCLUSION: Patients with squamous cell carcinoma treated on the CT + RT arm had a significant reduction of first DM other than brain, but there was difference in survival. Survival favored CT + RT in nonsquamous carcinoma despite similar failure patterns. Reasons for improved survival with CT + RT in NSCLC are not yet available.     

The fate of patients with locally advanced bladder cancer treated conservatively with neoadjuvant chemotherapy, extensive transurethral resection and radiotherapy: 10-year experience

PURPOSE: We assess the results of bladder preservation for infiltrating bladder cancer. The potential for neoadjuvant chemotherapy followed by extensive transurethral resection and radiotherapy was evaluated in 40 patients with T2-T4a G2-G3 bladder carcinoma. MATERIALS AND METHODS: From 1983 to 1995, 40 patients with bladder cancer underwent bladder sparing treatment, consisting of neoadjuvant chemotherapy, extensive transurethral resection and radiotherapy. Most patients had T3G3 cancer. A deep transurethral resection biopsy was performed before and after chemotherapy, and an extensive transurethral resection was repeated at the end of radiotherapy. Of the patients 30 received cisplatin and methotrexate and 10 also received vinblastine. Total dose of radiotherapy was 60 to 65 Gy. Recurrent superficial tumors were treated transurethrally. Radical cystectomy was considered for persistent or recurrent invasive disease. RESULTS: Complete response occurred in 19 patients (47.5%) after chemotherapy, and in 8 patients after transurethral resection and radiotherapy (67.5%). Within 10 years 8 responding patients (30%) had local recurrences and 3 underwent cystectomy. Of the patients 14 (35%) are alive, including 13 with no evidence of disease (mean survival 65 months), 5 died of unrelated disease and 21 (52.5%) died of distant metastases (mean survival 28 months). Of the 21 patients 14 had residual tumor after radiotherapy, 3 presented with distant metastases after vesical infiltrating recurrence and 4 had distant metastases in the absence of locoregional recurrence. In 22 patients (55%) the bladder was salvaged. Patients with complete response to chemotherapy had a low risk for recurrent infiltrating tumors and metastases. CONCLUSIONS: Complete tumor control was maintained at 5 years in more than 50% of the patients treated conservatively. Bladder salvage is feasible in select patients.     

The risk of acute leukemia in patients treated for Hodgkin's disease is significantly higher aft [see bined modality programs than after chemotherapy alone and is correlated with the extent of radiotherapy and type and duration of chemotherapy: a case-control study

BACKGROUND AND OBJECTIVE: Patients treated for Hodgkin's disease have an increased risk of developing subsequent acute leukemia. This co-operative study was conducted to assess the relative risk associated with several candidate factors including age, splenectomy, combined modality therapy and cumulative drug dose including alkylating agents and nitrosurea derivatives. DESIGN AND METHODS: This study evaluated the risk of acute leukemia according to pretreatment variables and therapy modalities among 1659 patients treated for Hodgkin's disease and followed for a median time of 10 years. Both case-control and actuarial risk studies were performed. Median age was 34 years (range: 12-83); 53% of patients were splenectomized. As to the overall therapy, 348 patients (21%) were given radiotherapy (RT) alone, 375 (23%) chemotherapy (CT) alone (including MOPP, MOPP + ABVD or MOPP + ABVD + lomustine); 936 (56%) received both CT and RT, either as primary or salvage treatment. RESULTS: The overall 15-year actuarial risk of leukemia was 4.2%; the hazard function curve showed two peaks of risk at the 3th and the 8th year from the initiation of therapy and no leukemia beyond the 12th year of follow-up. Risk of leukemia was 0.3% after RT alone, 2.8% after CT alone (2.2% after MOPP; 4.4% after MOPP + ABVD + lomustine), and 5.4% in patients given combined modality therapy (10.2% for RT + MOPP; 15.6% for RT + MOPP + lomustine). No leukemia occurred after ABVD alone and the risk was low (0.6%) when neither mechlorethamine nor lomustine were utilized. Patients who had received extended radiotherapy including abdomen and pelvis in addition to MOPP showed a significantly higher risk of leukemia compared to those given limited RT + MOPP (P = 0.01). Case-control analysis indicated advanced stage, type and duration (> 8 months) of CT and extension of RT as significant risk factors for leukemia. Compared to RT alone, the odds ratio was 5.9 after MOPP + extended RT, and 8 when a lomustine-containing regimen was used, as well. Neither age nor splenectomy were independent risk factors for leukemia; splenectomy was influential only when patients had been given MOPP chemotherapy, as well. INTERPRETATIONS AND CONCLUSIONS: Both case-control and actuarial analyses indicated that: a) combined modality therapy with MOPP and extensive RT (including abdomen and pelvis), and the use of lomustine added to the leukemogenic risk of MOPP alone; b) programs without mechlorethamine, procarbazine and lomustine were almost devoid of leukemogenic risk.     

Effect of EDTA on reduction of copper toxicity in Oreochromis mossambicus (Peters)

OBJECTIVES: To determine the best therapeutic approach for treatment of patients with urethral cancer according to tumor location and clinical-pathologic stage. METHODS: A retrospective review of 21 consecutive patients diagnosed with primary urethral carcinoma was performed. Clinical-pathologic staging, treatment modality, and outcome were analyzed. RESULTS: The overall survival rate was 62%. In patients with clinical Stage Ta-2N0M0 tumors, 8 of 9 patients (89%) are free of disease compared to 5 of 12 patients (42%) with Stage T3-4N0-2M0 tumors (P = 0.03). Best treatment outcome for patients with Stage T3 disease or higher was obtained when multimodality therapy (neoadjuvant chemotherapy and radiation therapy with or without surgery) was administered, with a disease-free survival rate of 60%. CONCLUSIONS: Clinical-pathologic stage was a strong predictor of disease-free survival rate. For patients with Ta-2N0M0 tumors, multimodality therapy may not be required. Conversely, best treatment outcomes in patients with T3-4N0-2M0 tumors are obtained by administering a multimodal therapy combining chemotherapy and radiation therapy with surgical resection.     

Combined surgery and postoperative radiotherapy for carcinoma of the base of radiotherapy for carcinoma of the base of tongue: analysis of treatment outcome and prognostic value of margin status

BACKGROUND: Choice of treatment for base of tongue carcinoma is controversial, with options including surgery alone, radiotherapy alone, or multimodality treatment. Given the highly aggressive nature of these tumors, it has been our institutional policy to manage this disease with combined partial glossectomy (with attempt to avoid laryngectomy if possible) with planned postoperative radiotherapy (RT). We reported on our institutional experience with this approach. METHODS: A retrospective review of the charts of 17 patients with primary base of tongue squamous cell carcinoma treated with surgery and postoperative RT was performed. Patients treated with chemotherapy as part of their management were excluded. All patients underwent partial, hemi-, or subtotal glossectomy; 15/17 patients underwent ipsilateral radical or modified radical neck dissection. All patients received comprehensive postoperative RT (median dose 6000 cGy; range 5040-6920 cGy). Stage distribution was as follows: stage I, 2; stage II, 3; stage III, 2; stage IV, 10. Positive margins for invasive carcinoma were found in 9/17 patients. Median follow-up of surviving patients is 46 months; median follow-up for all patients is 31 months. RESULTS: For the entire group of patients, the actuarial 3-year local-regional control rate was 68%. The actuarial 3-year overall survival rate was 46%. The local-regional control rate was 83% for patients with stage I-III disease versus 50% for stage IV disease. There were no local failures among eight patients with negative margins (local control 100%) compared with an actuarial local control rate of 36% among patients with positive margins (p = .03). Survival, disease-specific survival, and locoregional control were also highly correlated with margin status (p = .003). Late major complications included 5/17 patients requiring permanent G-tubes and/or tracheostomy to prevent aspiration. CONCLUSIONS: Surgery plus postoperative RT is an intensive treatment for carcinoma of the base of tongue which offers high locoregional control in patients in whom negative margins are achieved. Positive margins indicate a high risk of locoregional and systemic failure, and these patients should be considered for innovative clinical trials after surgery.     

Tissue preparation for immunocytochemistry

The results in 9 patients with unresectable recurrent squamous cell cancer of the head and neck who were treated with aggressive concurrent chemoradiotherapy are reported. Treatment consisted of one or two courses of chemotherapy with 5-fluorouracil 1000 mg/m2/day and cisplatin 20 mg/m2/day, both given as 4-day continuous intravenous infusions, concurrent with radiation therapy. Salvage radiation doses between 30 and 70 Gy were administered. Seven patients had previously undergone an attempt at curative surgery, and 7 had been treated with radiation doses between 52 and 72 Gy. The recurrent disease was locally confined in 3, locoregional in 5, and locoregional with metastases in 1 of the 9 patients. Treatment toxicity was significant and included mucositis, nausea/vomiting, and granulocytopenia, but there were no toxic deaths. Complete tumor clearance was possible in 6 of these 9 patients, and 5 patients remain disease-free at 41+, 43+, 45+, 47+, and 50+ months. Of these 5 patients, 4 had previously been treated with both surgery and radiation, while 1 had only undergone surgery. We conclude that aggressive chemotherapy and concurrent (re)irradiation can be given to patients with unresectable, recurrent, squamous cell cancer of the head and neck. Treatment is tolerable, and disease-free long-term survival is possible. Careful patient selection, however, is required.     

Limb salvage and outcome of osteosarcoma. The University of Muenster experience

One hundred thirty-six patients with non-metastatic high grade osteosarcoma treated from 1978 to 1994 in one institution with a multidisciplinary approach that included intravenous neoadjuvant chemotherapy were studied to evaluate which factors influence the outcome of modern orthopaedic therapy. Anatomic location, tumor volume, surgical margins, complications, and functional outcome were analyzed. Seventy-nine patients had a limb salvage procedure, 21 had a rotationplasty, and 33 had an amputation. Limb salvage consisted of 32 endoprostheses, 39 allograft replacements, six autograft replacements, and two shortening procedures. Three patients died during preoperative chemotherapy treatment. At a mean followup of 43 months, 81 patients continue to be disease free, three are alive after local recurrence, 17 are alive after having metastatic lesions, five are alive with metastatic lesions present, and 30 patients died of their disease. Forty-seven patients had pulmonary metastatic lesions, 14 had osseous metastatic lesions, three had abdominal metastatic lesions, two had lymphatic metastatic lesions, and eight patients had skip metastatic lesions. Prognosis correlated with chemotherapy response, surgical margins, and tumor volume. The minor complication rate for limb salvage was 4% and the major complication rate was 52%. Amputations had a 6% minor complication rate and 34% major complication rate. Rotationplasties had 10% minor and 48% major complication rates. The Musculoskeletal Tumor Society functional evaluation after limb salvage showed that 23 (38%) patients had more than 75% of the maximum functional score, 34 (56%) were from 50% to 75%, and three (5%) less than 50%. Of the rotationplasties, six (67%) were functionally better than 75% and three (33%) were functionally better than from 50% to 75%. In the group of amputations, 13 (56%) were from 50% to 75%, and 10 (44%) less than 50%. The extent of preoperative necrosis, surgical margins, and tumor volume are the most important prognostic factors. The increase in limb salvage procedures and the better long term survival of patients results in a higher rate of immediate and delayed complications. Functional outcome after rotationplasty is superior to limb salvage reconstruction and amputation.     

The management of stage I testis cancer

For clinical stage I seminoma, conventional management consists of adjuvant RT after orchiectomy. Only 5% of patients relapse. The majority can be salvaged by chemotherapy. The overall survival of 98% is excellent. Seminoma is radiosensitive. A lower dose of RT is required than for NSGCT. Standard therapy presently is 30 Gy in 3 weeks, as suggested by the MRC study. RT is generally well tolerated. There have been recent concerns about second malignancies after 10 to 15 years. Surveillance studies have shown that 18% of patients relapse, the majority in para-aortic lymph nodes. About 15% require salvage RT and 5% salvage chemotherapy. Second relapses are seen in patients treated with RT at first relapse, and occur outside of the radiation field. The main advantage of surveillance is that 80% of patients can be spared slightly toxic overtreatment. The main disadvantage is the need for long-term follow-up, which is expensive and stressful to the patient. Good patient compliance, mandatory to an observation policy, is often difficult on a long-term basis. Seminoma is clearly responsive to chemotherapy. Adjuvant carboplatin in clinical stage I has only been evaluated in two studies. Because reliable prognostic factors have not been established, a high-risk group cannot be identified, and chemotherapy must be given to all patients. Whether or not one cycle of chemotherapy is sufficient requires further confirmation, particularly in view of the results with carboplatin as compared with cisplatin in patients with advanced NSGCT. Results of the randomized MRC trial comparing RT with carboplatin are of interest.     

Combined-modality therapy for squamous carcinoma of the buccal mucosa: treatment results and prognostic factors

BACKGROUND: Reports on locoregional control and survival of squamous cell carcinoma of buccal mucosa are scarce in literature. In this study, a single institutions's experience of combined surgery and postoperative radiotherapy (RT) for buccal mucosal malignancy with favorable results was analyzed and presented. The prognostic factors on locoregional control were also discussed. METHODS: From January 1988 to July 1994, 57 patients with squamous cell carcinoma of buccal mucosa treated by surgery and RT were reviewed. The distributions according to American Joint Committee on Cancer (AJCC) staging were: stage II, 6; stage III, 21; and stage IV, 30 patients. Total dose of RT at the buccal area ranged from 45 Gy to 68.4 Gy, median 61.2 Gy. Tumor-related factors (AJCC stage, T stage, histologic grading, pathologic tumor invasion to skin of cheek, adjacent bony structures, and regional lymph nodes) and treatment-related factors (surgical margin, radiation dose, and the time interval between operation and RT) were analyzed to determine their influence on locoregional control. RESULTS: Three-year actuarial locoregional control rate, overall survival rate, and disease-specific survival rates were 64%, 55%, and 62%, respectively. Ten of these 22 patients (45%) with recurrent tumors were reoperated, but only 2 patients were successfully salvaged. Positive surgical margin and tumor invasion to skin of cheek were significantly poor prognostic factors on locoregional control by univariate analysis. In multivariate analysis, tumor invasion to skin of cheek was the only prognostic factor (p = .0014). CONCLUSIONS: Locoregional failure was the major cause of death for squamous buccal mucosa cancers managed with surgery and RT. Few recurrences could be detected early and successfully salvaged. Skin of cheek involvement is an important prognostic factor for buccal mucosa cancers.     

Locally recurrent soft tissue sarcoma of the extremities

BACKGROUND: The management of locally recurrent extremity soft tissue sarcoma remains challenging. This study was undertaken to evaluate the long-term outcome after therapy for isolated locally recurrent soft tissue sarcoma (STS) of the extremity. METHODS: Between January 1, 1980, and December 31, 1990, 52 patients were treated at The University of Texas M. D. Anderson Cancer Center for locally recurrent extremity STS. The records of the subset of these patients (n = 36) with isolated local recurrence were examined to document clinicopathologic and treatment factors and to evaluate outcome using the end points of local recurrence-free, recurrence-free, and overall survival. RESULTS: Limb-sparing conservative surgery was possible in 24 patients (75%). Twelve (33%) of 36 patients were treated by surgery alone, 23 patients (64%) were treated with combined modality therapy (surgery plus radiation and/or chemotherapy), and 1 patient had radiotherapy only. Sixteen (44%) of 36 patients had no further recurrence of any type at a median follow-up of 58 months (range, 4 to 173 months). The 5-year actuarial local recurrence-free, recurrence-free, and overall survival rates were 72%, 45%, and 77%, respectively. CONCLUSIONS: Limb-sparing conservative surgery is possible in the majority of patients with isolated locally recurrent STS. Durable local control can be established with individualized local treatment strategies. These results support aggressive multimodality limb-sparing treatment approaches for these patients.     

Head and neck cancer: guidelines for chemotherapy

Head and neck cancer is estimated to be one of the most prevalent cancers in the world. This tumour type accounts for 5% of all new cancer cases in the US and Europe each year. Patients with locally recurrent or metastatic squamous cell carcinoma of the head and neck have a poor prognosis, with a median duration of survival between 4 and 6 months. During the past few years, screening for potentially active new compounds, new associations and new modalities of chemotherapy administration have had some degree of success. Clinical investigations have also focused on the addition of chemotherapy to locoregional treatment for patients with locally advanced disease. Induction chemotherapy or concomitant chemo- and radiation therapy can result in high response rates, and reduced incidence of distant metastases. However, there is no clear demonstration of any benefit from the addition of chemotherapy to locoregional therapy on overall survival in patients with resectable disease. In patients with resectable laryngeal or hypopharyngeal cancer, chemotherapy combined with radiotherapy can be considered as a standard treatment option for larynx preservation, keeping total laryngectomy reserved for salvage therapy. In patients with unresectable head and neck cancer, simultaneous chemoradiotherapy has been shown to improve locoregional control and survival, at the cost of greater toxicity. Outside clinical trials, this approach can also be considered as a standard therapy for unresectable disease.     

A fearsome enemy (1); A history of sanitation in the British Army 1899-1914

This study presents the results of a prospective study of methyl-gag, ifosfamide, methotrexate and etoposide (MIME) as salvage regimen for Hodgkin's disease (HD) in Sweden. Sixty-four patients with recurrent or refractory HD were treated with MIME between July 1988 and December 1993. All patients except one had, earlier, been treated with and failed consecutive or alternating MOPP and ABVD. Median age was 37 yr (range 14-73). Twenty patients (31%) achieved a complete remission (CR) and 17 (27%) a partial remission (PR), giving an overall response rate of 58%. The 5-yr survival for all patients was 43%. In a multivariate analysis, the most important factors predicting a poor survival were the presence of extranodal disease at relapse, male gender and high age. Twenty-nine patients were treated with high-dose chemotherapy with stem-cell rescue after MIME. Those patients had a similar survival compared to the patients responding to MIME but not treated with high-dose chemotherapy. We conclude that MIME induces remissions in a high proportion of patients with recurrent and refractory HD with acceptable toxicity. The remissions probably need consolidation, but the nature of this consolidation is still controversial.     

Multimodality therapy of late stage lung cancer

A prospective randomized study of 80 cases of stage III lung cancer treated with different multimodality therapy was carried out. Life table and Kaplan-Meir curve were employed to calculate survival rate. Log rank-multivariate analysis and time t test were used to evaluate statistical values of the 80 cases, 40 SCLC were randomly treated with either chemotherapy (CT)-surgery-CT or CT-radiotherapy (RT)-CT. The year survival rates were better in the group treated with CT-surgery-CT, a statistical difference was observed in 2yr survival rate (P < 0.05). Thus, surgical resection for SCLC was better than RT after CT. The remaining 40 cases of NSCLC were randomly treated with either CT-RT-CT or RT-CT. Multivariate analysis showed a better statistical meaning in the 20 cases treated with CT-RT-CT than the other group, their 1, 2 year survival rates were 27%, 40% and 22%, 15%, respectively. Thus preradiative CT was beneficial for survival.     

Clinical stage IE primary lymphoma of the nasal cavity: radiation therapy and chemotherapy

PURPOSE: To determine the appropriate radiation therapy and chemotherapy for primary lymphoma of the nasal cavity to improve the local control and survival rates. MATERIALS AND METHODS: Of the 25 adult patients with stage IE nasal lymphoma, nine underwent local radiation therapy alone and 16 underwent radiation therapy and chemotherapy (intravenous infusion). Radiation doses to the involved area were 22-54 Gy (median dose, 49 Gy). RESULTS: The 5- and 10-year cause-specific survival rates were 91% and 73%, respectively. The 5- and 10-year disease-free survival rates were 83% and 59%, respectively. Eight patients developed recurrent disease: six at the local site, one in the cervical nodes, and one in the small intestine. Five of the six patients with local recurrence received less than 50 Gy. Four of the six patients developed recurrent disease in the treated area; the other two patients developed marginal recurrences. Prognostic factors such as age, sex, maximum tumor size, and lactate dehydrogenase level were of limited value. CONCLUSION: The most common recurrence site was the local site. To improve the local control rate, the involved area should be treated with high-dose radiation therapy. The clinical results did not demonstrate the usefulness of combination chemotherapy for stage IE nasal lymphoma.     

Pharmacokinetics of CDDP by the route of administration in patients with ovarian cancer

Seventy patients with local squamous cell carcinoma of the esophagus were treated between 1981 and 1990 with preoperative chemotherapy, surgical resection, and possible postoperative radiation therapy and/or chemotherapy. Chemotherapy included two cycles of 5-fluorouracil (1000 mg/m2) by continuous intravenous infusion on days 1-4 and cisplatin (100 mg/m2) on day 4. Complete clinical response (CCR) was achieved in 28 (41%) patients, partial clinical response (PCR) in 17 (25%), and no response in 23 (34%). Fifty-five (81%) patients were resected, 6 (9%) were explored, and 7 (10%) were unable to have surgery. Microscopic analysis of 55 resected patients showed 50 (91%) with active tumor, 1 (2%) with necrotic tumor, and 4 (7%) with a pathological complete response to chemotherapy. Twenty-six of the 55 resected patients (47%) had no gross evidence of disease at the time of surgical inspection. Median overall survival was 21.86 months (range 2-107 months) for all patients and 26.71 months (range 2-107 months) for resected patients. Actuarial 5-year survival rate was 31% for all patients and 39% for resected patients. Prolonged survival correlates with complete clinical response to chemotherapy, low pathological stage of disease, and successful resection of the lesion.     

Topical nitroglycerin in the management of anal fissure: an explosive outcome!

Anal sphincter spasm is a common finding in patients with anal fissure disease. It is postulated that spasm impedes mucosal blood flow and impairs healing. Topical nitroglycerin (NTG), a nitric oxide donor compound, has been shown to cause relaxation of the anal sphincter and may have treatment efficacy in the management of anal fissure. The purpose of this study was to assess the usefulness of NTG for anal fissure. We performed a retrospective review of patients with anal fissure treated with various concentrations of topical NTG ointments over an 18-month period ending July 1997. Of the 81 patients studied, 44 (54%) were male. There were 42 acute and 39 chronic fissures. NTG preparations included 1 per cent isosorbide (n = 37), 0.2 per cent NTG (n = 38), and 0.5 per cent NTG (n = 6). Healing with NTG therapy occurred in 29 acute (69%) and 21 chronic fissure (54%) patients. There was no difference in the incidence of healing of acute or chronic fissure between the various NTG treatment preparation groups. When acute and chronic fissure therapy was subdivided by time of NTG treatment (immediate versus post-conservative therapy failure (PCF)), 14 (74%) of acute PCF and 5 (42%) of chronic PCF patients healed. We conclude that no single formula was superior. When patients were subdivided into a PCF group, NTG therapy demonstrated a significant salvage rate, thus avoiding surgery.     

Loss of heterozygosity at 11q23 in squamous cell carcinoma of the head and neck is associated with recurrent disease

Loss of heterozygosity (LOH) at chromosome 11q23 has been found in a variety of epithelial human neoplasms, suggesting that this region contains a tumor suppressor gene(s) important to tumorigenesis. We investigated whether LOH at 11q23 could be detected in squamous cell carcinoma of the head and neck (SCCHN), and whether loss at this site was associated with specific clinical parameters. Fifty-six matched blood and SCCHN tumor samples taken at the time of diagnosis were evaluated for LOH at three microsatellite markers at 11q23. Multiplex PCRs with [alpha-32P]dCTP labeling of the amplified DNA strands were performed. Clinical data were obtained from medical record review. LOH at 11q23 was found in 13 of 52 (25%) evaluable tumors. There was no association between LOH at 11q23 and amplification of the CCND1 (cyclin D1) oncogene or inactivation of the p53 gene, which had been determined previously. With a mean follow-up of 24 months, an association independent of tumor size or stage was found between LOH at 11q23 and recurrent disease (P = 0.04). Among subjects who received radiotherapy (RT) as a component of their treatment, LOH at 11q23 was associated with persistent or recurrent locoregional disease (P = 0.05). LOH at 11q23 occurs in a subset of SCCHN. It is associated with a higher likelihood of recurrent disease, perhaps related to resistance to RT. The specific gene(s) and mechanism(s) responsible remain to be identified. Until then, LOH at 11q23 might become a marker identifying patients likely to do poorly with conventional therapy.