Results of radical surgical procedures after radiation for treatment of invasive carcinoma of the uterine cervix in a private practice

An analysis is made of the results of treatment of 96 women with carcinoma of the cervix, Stages IB and II, in a private practice. All 96 women were treated preoperatively with uterine intracavitary radium, followed 6 weeks later by Wertheim hysterectomy with pelvic lymphadenectomy. If malignant tumor was present in the lateral pelvic lymph nodes, external radiation was given postoperatively. The over-all survival rates were: Stage IB, 88% and 84% at 5 and 10 years; Stage II, 72% and 62% at 5 and 10 years. Regardless of the clinical stage, the highest survival rates were found in those patients who had no malignancy in the lateral pelvic lymph nodes and no residual cervical carcinoma. The lowest survival rates were found in those patients who had both residual cervical carcinoma and lymph node metastases.     

Calcium antagonists--pharmacologic considerations

BACKGROUND: The authors evaluated the impact of body mass on survival and morbidity of patients with new International Federation of Gynecology and Obstetrics (FIGO) Stage IB1 and IB2 cervical carcinoma managed with radical hysterectomy. METHODS: Two hundred twenty-nine patients with Stage IB1 or IB2 cervical carcinoma treated with radical hysterectomy were studied in a multivariate logistic regression analysis. The body mass index (BMI) and the ponderal index (PI) were used as measures of body mass and were analyzed as predictors of recurrence, survival, and complications in light of the new staging system. RESULTS: Twenty-seven of 229 patients died of recurrent disease. A low BMI or a high PI were predictive of poor survival. Tumor greatest dimension, lymph node involvement, BMI, and PI were all independent predictors of survival (P=0.0006). The only independent predictor of complications was para-aortic lymph node dissection (P=0.0026). CONCLUSIONS: Cervical carcinoma patients with a low body mass, as indicated by a low BMI or a high PI, were found to have poor survival after undergoing radical hysterectomy. Additional predictors of poor survival included lymph node metastases and increased tumor size. BMI and PI are more important predictors of survival than the new FIGO Stages IB1 and IB2. Body mass is not predictive of complications.     

Radiotherapy and chemotherapy for invasive thymomas: a multicentric retrospective review of 90 cases. The FNCLCC trialists. Fédération Nationale des Centres de Lutte Contre le Cancer

PURPOSE: Thymoma is a rare disease. The treatment of patients with invasive thymoma remains controversial. The prognosis of such patients is poor, even with the use of postoperative radiation therapy and chemotherapy. We retrospectively reviewed the outcome and prognostic factors in a series of 90 patients presenting with an invasive thymoma treated by partial resection or biopsy and radiation therapy. METHODS AND MATERIALS: From 1979-1990, 163 patients with the diagnosis of lymphoepithelial thymoma were treated in 10 French cancer centers. Patients were staged using the postoperative "GETT" classification derived from that of Masaoka. Ninety patients who presented with an invasive thymoma, 58 Stage III (21 IIIA: partial resection and 37 IIIB: biopsy) and 32 Stage IVA (intrathoracic thymoma spread), are the subject of this report. Treatment combined surgery and radiation therapy (+/- chemotherapy), with curative intent. Surgery consisted of partial resection in 31 patients (21 Stage III), and biopsy in 55 patients (37 Stage III). The median radiation dose to the tumor was 50 Gy (30-70 Gy). Supraclavicular radiation was performed in 59 patients (median dose 40 Gy). Chemotherapy, combined with radiation in 59 patients, consisted of multidrug regimens, mainly platinum based. RESULTS: The median follow-up is 105 months (20-165 months). The 5- and 10-year overall survival rates are 51 and 39%, respectively. There is a great impact of the extent of surgery on survival: the 5- and 10-year survival rates were 64% and 43%, respectively, after partial resection, compared to 39% and 31% after biopsy (p < 0.02). Local control at 8.5 years was obtained in 59 of 90 patients (66%): 40 Stage III, 19 Stage IVA. There is a significant relationship between the extent of surgery and the local control (16% of relapse after partial resection vs. 45% after biopsy, p < 0.05). Seven patients developed significant (grades 3-4 WHO grading system) treatment-induced side effects. Stage, histologic type, and chemotherapy were not prognostic factors. CONCLUSION: In this large multicentric retrospective study of invasive thymomas (Stage III-IVA) treated by surgery and radiation, results show the importance of loco-regional treatments, such as surgery and radiation therapy. There is also a great impact of radiation on local control. However, the rate of local recurrence (34%) justifies recommending a higher dose of radiation (> 50 Gy) than doses used in this study, for incompletely resected patients. The role of chemotherapy needs to be further assessed.     

Sequencing of the alpha-synuclein gene in a large series of cases of familial Parkinson''s disease fails to reveal any further mutations. The European Consortium on Genetic Susceptibility in Parkinson''s Disease (GSPD)

PURPOSE: Tumor hypoxia may be an important factor predicting relapse following radiation therapy. This study was designed to determine the relationship between the oxygenation parameters measured using a polarographic oxygen electrode, prior to and during treatment in patients with cervix cancer, and to assess these results with regard to patient survival. MATERIALS AND METHODS: Forty-three patients had pretreatment oxygen assays performed and measurements repeated following external beam radiation to a median dose of 50 Gy (range 26-52 Gy). Stage distribution showed 15 patients in Stage IB, 17 in Stage II, and 11 in Stage III. The median tumor size was 5 cm (range 3-10 cm). RESULTS: The median proportion of pO2 values <5 mm Hg (the HP5) was 41% following radiation, and the median pO2 was 12 mm Hg. These results were not significantly different from the pretreatment HP5 or pO2 of 37% and 12 mm Hg, respectively. Disease-free survival at 2 years was 50% in patients with posttreatment HP5 < or =50%, compared to 60% when posttreatment HP5 was >50% (p = 0.35). CONCLUSIONS: Unlike pretreatment results, tumour oxygenation measured following external radiation does not appear to be a useful predictive assay in patients with cervical cancer.     

Results of postoperative radiotherapy of cervix carcinoma after radical versus non radical hysterectomy

We studied the outcome of our 68 cervix carcinoma patients treated either with: 1) radical surgery and postoperative 192Ir high-dose rate afterloading brachytherapy or postoperative radiotherapy to the whole pelvis or with 2) standard hysterectomy and postoperative radiotherapy to the whole pelvis. Forty-eight women were treated by radical hysterectomy from 1988 to 1992 and--due to risk factors--by postoperative radiotherapy (Group 1), 20 other patients (Group 2) pretreated with standard hysterectomy were admitted to the university hospital for postoperative radiotherapy of the whole pelvis. Postoperative radiotherapy consisted of 39.6 Gy total dose using the box technique, plus two afterloading applications with a single dose of 7.5 Gy and 6 Gy external beam therapy to the pelvic lymph nodes sparing the midline. Comparing the Kaplan-Meier plots of both groups, the tumor related survival curve, the locoregional control and the rates of metastatic disease were nearly identical. But in the analysis of special subgroups, patients with positive lymph nodes after standard hysterectomy and postoperative radiotherapy had a worse prognosis (75% three years' survival rate) than patients after radical surgery (86% three years' survival rate). Lymphangiosis was a negative prognostic factor for the patients pretreated with standard hysterectomy (60% versus 80% three years' survival rate), but not for patients after radical surgery (80% three years' survival rate), despite the same radiotherapy in both groups. CONCLUSION: Standard hysterectomy fails to be an adequate treatment for early cervix carcinoma because moderately dosed postoperative radiotherapy cannot achieve complete locoregional control in all cases of positive lymph nodes or invasion of lymph vessels. However, based on the empirical results of many authors and our own results, postoperative radiotherapy is further indicated in high risk cases of cervix carcinoma after radical surgery.     

Radiation therapy results for patients undergoing inappropriate surgery in the presence of invasive cervical carcinoma

Total vaginal or abdominal hysterectomy was considered an inadequate treatment method for invasive uterine cervix cancer. Usually the procedure was inadvertently performed on patients who were thought preoperatively to have benign or premalignant conditions. Between 1985 and 1993, 64 patients undergoing hysterectomy in the presence of invasive cervical cancer were treated with external radiation therapy and/or intracavitary radiotherapy. Preoperative diagnoses were carcinoma in situ (36), severe dysplasia (2), and early invasive cancer (14), and others were benign disease. Overall 5-year survival and relapse-free survival rates were 75.8 and 77.5%, respectively. For patients in retrospective stage IA, IB, and IIB (gross residual after surgery), overall 5-year survival rates were 90.9, 88.8, and 27.9%, respectively. Thirteen patients developed treatment failure; most of them (10/13) were patients with gross residual disease. Patients with early invasive cervical cancer (stage IA) had no treatment-related failure. Prognostic factors affecting survival by univariate analysis were retrospective stage (P = 0.0000) and preoperative diagnosis (P = 0.0021). Tumor histology was marginally significant factor (P = 0.0938). By multivariate analysis, only retrospective stage was significant prognostic factor (P = 0.0001). Adjuvant radiotherapy appears to be an effective treatment method for patients with presumed stage IA and IB after inadvertent hysterectomy. Survival for patients with gross disease remaining after inappropriate hysterectomy is poor. So, early cancer detection and proper management with precise pretreatment staging is necessary to avoid inadherent hysterectomy, especially in cases of gross residual disease.     

Carcinoma of the nasopharynx in young patients

PURPOSE: To provide an analysis of eighteen cases of adolescent nasopharyngeal carcinoma treated between 1971 and 1989. METHODS AND MATERIALS: Between 1971 and 1989, 48 cases of nasopharyngeal carcinoma were evaluated at the Medical College of Georgia Hospital and Clinics. Eighteen patients between the ages of 9 and 29 years were treated at the Georgia Radiation Therapy Center. All patients presented for treatment with (AJCC) Stage IV disease. Fifteen patients with lymphoepithelioma and three with squamous cell carcinoma histologies received definitive radiation therapy to a median dose of 64.8 Gy. Males outnumbered females by more than 2:1 and the majority of patients (67%) were black. Nine patients received multiagent adjuvant chemotherapy. RESULTS: Thirteen patients are alive from 7 to 166 months (median 32 months) including three with disease at 17, 24, and 132 months. Overall and disease-free survival at 5 and 10 years were 63% and 54%, respectively. Five patients died from disease; four patients had pulmonary metastases while one had CNS metastasis. Eighty percent of relapses occurred within the first 2 years following treatment. Acute and chronic toxicities were limited, consisting primarily of mucositis and xerostomia. Radiation doses of 65 Gy or more (p = 0.049) and age greater than 20 years (p = 0.005) were positive prognosticators for survival. Adjuvant chemotherapy, race, and sex were not found to be of prognostic value. Disparities in the distribution of patients with lymphoepithelioma and squamous cell histologies and the presentation of advanced regional disease precluded analysis for prognostic significance of histology and nodal status in this series. CONCLUSION: The results of the present series compare favorably with those published from other institutions. High doses of radiation and a high systemic failure rate continue to be the fundamental obstacles to effective management and enhanced survival for patients with nasopharyngeal carcinoma.     

Cervical carcinoma metastatic to para-aortic nodes: extended field radiation therapy with concomitant 5-fluorouracil and cisplatin chemotherapy: a Gynecologic Oncology Group study

PURPOSE: A multicenter trial of chemoradiation therapy to evaluate the feasibility of extended field radiation therapy (ERT) with 5-fluorouracil (5-FU) and cisplatin, and to determine the progression-free interval (PFI), overall survival (OS), and recurrence sites in patients with biopsy-confirmed para-aortic node metastases (PAN) from cervical carcinoma. METHODS AND MATERIALS: Ninety-five patients with cervical carcinoma and PAN metastases were entered and 86 were evaluable: Stage I--14, Stage II--40, Stage III--27, Stage IVA--5. Seventy-nine percent of the patients were followed for 5 or more years or died. ERT doses were 4500 cGy (PAN), 3960 cGy to the pelvis (Stages IB/IIB), and 4860 cGy to the pelvis (Stages IIIB/IVA). Point A intracavitary (IC) doses were 4000 cGy (Stages IB/IIB), and 3000 cGy (Stages IIIB/IVA). Point B doses were raised to 6000 cGy (ERT + IC) with parametrial boost. Concomitant chemotherapy consisted of 5-FU 1000 mg/m2/day for 96 hours and cisplatin 50 mg/m2 in weeks 1 and 5. RESULTS: Eighty-five of 86 patients completed radiation therapy and 90% of patients completed both courses of chemotherapy. Gynecologic Oncology Group (GOG) grade 3-4 acute toxicity were gastrointestinal (18.6%) and hematologic (15.1%). Late morbidity actuarial risk of 14% at 4 years primarily involved the rectum. Initial sites of recurrence were pelvis alone, 20.9%; distant metastases only, 31.4%; and pelvic plus distant metastases, 10.5%. The 3-year OS and PFI rate were 39% and 34%, respectively, for the entire group. OS was Stage I--50%, Stage II--39%, and Stage III/IVA--38%. CONCLUSIONS: Extended field radiation therapy with 5-FU and cisplatin chemotherapy was feasible in a multicenter clinical trial. PFI of 33% at 3 years suggests that a proportion of patients achieve control of advanced pelvic disease and that not all patients with PAN metastases have systemic disease. This points to the importance of assessment and treatment of PAN metastases.     

Combined radiation therapy and cisplatin for locally advanced carcinoma of the urinary bladder

BACKGROUND: This study evaluates feasibility and results of combined treatment of cisplatin and radiation therapy for patients with inoperable invasive bladder carcinoma. METHODS: From January 1988 to October 1991, 69 patients received radiation therapy and concomitant cisplatin. Median age was 71 years. Most tumors were locally advanced and high grade. A macroscopically complete transurethral resection was performed initially in 18 patients. Dose of pelvic radiation ranged from 40 Gy to 45 Gy, and total dose to the bladder ranged from 55 Gy to 60 Gy. Concomitant continuous cisplatin infusion at a dose of 20-25 mg/m2/day for 5 days was delivered during the 2nd and 5th weeks of radiation. RESULTS: As of April 1993, the median follow-up time was 36.4 months (range, 18-70 months). Ninety-one percent of the patients completed radiation therapy as planned, and 78.3% completed two courses of chemotherapy. Despite one treatment-related death due to renal failure, toxicity was generally mild and acceptable. Sixty-three patients were evaluable for response. Forty-eight patients (76.2%) achieved a complete response. Actuarial overall 3-year survival rate was 37.1% for all patients. Among the patients who experienced complete response, the 3-year actuarial local control and disease-free survival rates were 65.4% and 56.3%, respectively. Twenty-six patients (37.7%) are alive and disease-free with bladder preservation. One patient is alive and disease-free after salvage cystectomy. CONCLUSIONS: Concomitant cisplatin and radiation therapy offers high probability of complete response and local control in patients with invasive bladder cancer unsuitable for surgery. These results provide a basis for randomized studies comparing this approach with conventional therapy for patients with operable carcinoma.     

Pregnancy in a Jehovah's witness with cervical cancer and anemia

A 34-year-old Jehovah's Witness presented with vaginal bleeding and anemia at 23 weeks gestation. She was diagnosed with a FIGO Stage IB2 squamous cell carcinoma of the cervix. The patient refused transfusion of blood products and strongly desired to continue the pregnancy. She was hospitalized and at 33 weeks gestation underwent a Cesarean-radical hysterectomy with measures that minimized blood loss.     

Analysis of the results of combined therapy for maxillary carcinoma

BACKGROUND: Maxillary sinus carcinomas usually are locally advanced. A wide variety of modalities, including surgery, radiation therapy, and intraarterial chemotherapy, alone or in combination, have been used. However, there is still much controversy with regard to the optimum treatment. METHODS: From 1972 to 1986, 108 patients with squamous cell carcinoma of the maxillary sinus were treated at the Department of Radiology, University of Tokyo Hospital. From 1972 to 1974 (the first period), the treatment consisted of operation for reduction of tumor volume, daily cleaning of the maxillary antrum, 20 Gy of postoperative radiation therapy, and intraarterial infusion of 1500 mg of 5-fluorouracil (5-FU) and 3000 mg of 5-bromodeoxyuridine (BUdR). From 1975 to 1979 (the second period), the radiation dose was reduced to 10 Gy, and intraarterial infusion of 5-FU and BUdR was not performed. Surgery for reduction of tumor volume and daily cleaning of the antrum played a major role in this period. From 1980 to 1982 (the third period), daily cleaning of the antrum was not performed. Instead, the dose of radiation was increased to 50-60 Gy. From 1983 to 1986 (the fourth period), more extensive surgery to resect the tumor en bloc was introduced. The radiation dose was increased to 70 Gy. Intraarterial infusion of 3750 mg of 5-FU and 120 mg of cisplatin also was administered. RESULTS: The 5-year survival rate was 46% in the first period, 24% in the second period, 7.2% in the third period, and 53% in the fourth period. In the third period, there were more cases in which death resulted from a cause other than local failure, such as distant metastasis, pneumonia, or secondary primary cancer. Since 1984, we planned treatment with computed tomography (CT) and used the linear accelerator with a multileaf collimator to treat patients with an irregular field of irradiation. These have made it possible to administer radiation therapy in doses as high as 70 Gy without severe complications and improve the survival rate, especially for T4 disease. CONCLUSIONS: Radiation plays an important role in sterilizing malignant cells that cannot be removed by operation. The dose of radiation should be determined according to the volume of residual tumor. Careful treatment planning is required to irradiate the tumor adequately and reduce complications.     

Nasopharyngeal carcinoma in childhood and adolescence

BACKGROUND: This study reviews the authors' experience from 1979 through 1996 in the management and outcome of 56 patients with nasopharyngeal carcinoma who were under 20 years of age. PROCEDURE: There were 33 males and 23 females, their ages ranging from 7 to 19 years (median: 16 years). Forty patients had World Health Organization type III carcinomas, 16 had T4 tumors, 41 had metastatic cervical lymph nodes, and 50 were at stage III or stage IV. Thirty-two patients were treated with radiation therapy alone and 24 with the addition of chemotherapy. Cumulative radiation dose to the primary tumor ranged from 18 to 70 Gy (median: 66 Gy) and radiation dose to metastatic cervical lymph nodes ranged from 18 to 70 Gy (median: 66 Gy). RESULTS: Follow-up ranged from 0.1 to 16.8 years (mean: 9 years). Locoregional tumoral complete response was achieved in 49 patients. Locoregional tumoral failure was observed in 12 patients and systemic failure in 11. Overall, locoregional failure-free, metastases-free, and disease-free survival rates at 5 years were 49%, 62%, 79%, and 47%, respectively, for the entire group of patients, 42%, 61%, 72%, and 42%, respectively, for patients treated with radiation therapy alone, and 58%, 63%, 87%, and 54%, respectively, for patients treated with the addition of chemotherapy. Advanced T-stage and lower radiation doses worsened locoregional failure-free survival, whereas advanced N-stage and exclusion of chemotherapy worsened metastases-free survival. CONCLUSIONS: In children and adolescents with nasopharyngeal carcinoma, radiation therapy alone results in an improved locoregional tumoral response rate and a reduced locoregional tumoral failure rate at higher radiation doses, while the addition of chemotherapy results in a reduced systemic failure rate.     

High-dose-rate intracavitary brachytherapy in the management of cervical and vaginal intraepithelial neoplasia

PURPOSE: To assess the effectiveness of high-dose rate intracavitary brachytherapy (HDR-ICR) in patients with grade 3 cervical intraepithelial neoplasia (CIN-3) and grade 3 vaginal intraepithelial neoplasia (VAIN-3). METHODS AND MATERIALS: This was a retrospective analysis in 20 patients with CIN-3 (n = 14) or VAIN-3 (n = 6), average age 61.9 years, managed with HDR-ICR at Kanagawa Cancer Center. Two patients with CIN-3 with microinvasive foci and 11 other patients with CIN-3 were treated with HDR-ICR for cervical lesions. Six patients with CIN-3 after hysterectomy received HDR-ICR for recurrent or residual VAIN-3 lesions. One patient received radiation therapy for both CIN-3 and VAIN-3 lesions. All these patients but one were postmenopausal. RESULTS: Seventeen patients were treated with HDR-ICR alone, and three with combined external radiation therapy. The dose was calculated at Point A located 2 cm superior to the external os and 2 cm lateral to the axis of the intrauterine tube for intact uterus. For lesions of the vaginal stump, the dose was calculated at a point 1 cm superior to the vaginal apex or 1 cm beyond vaginal mucosa. In the 14 patients treated for CIN-3 lesions, the mean total dose of HDR-ICR was 26.1 Gy (range 20-30). Six patients received HDR-ICR for VAIN-3 lesions with mean dose of 23.3 Gy (range 15-30). At follow-up (mean 90.5 months; range 13-153), 14 patients were alive and 6 had died owing to nonmalignant intercurrent disease. No patient developed recurrent disease. Rectal bleeding occurred in three patients, but this symptom subsided spontaneously. Moderate and severe vaginal reactions were noted in two patients, in whom the treatment had included the entire vagina. CONCLUSIONS: HDR-ICR can be employed as the primary management strategy for postmenopausal women with CIN-3. In intraepithelial neoplasia involving the vaginal wall after hysterectomy, HDR-ICR should be considered as an alternative to total vaginectomy.     

Molecular and pharmacological characterization of recombinant rat/mice N-methyl-D-aspartate receptor subtypes in the yeast Saccharomyces cerevisiae

PURPOSE: To assess the local control and survival in patients who received pelvic irradiation for locally recurrent rectal carcinoma. METHODS AND MATERIALS: The records of 519 patients with locally recurrent rectal carcinoma treated principally with external-beam radiation therapy between 1975 to 1985 at a single institute were retrospectively reviewed. These included 326 patients who relapsed locally following previous abdominoperineal resection, 151 after previous low anterior resection, and 42 after previous local excision or electrocoagulation for the primary. No patients had received adjuvant radiation therapy or chemotherapy for the primary disease. Concurrent extrapelvic distant metastases were found in 164 (32%) patients at local recurrence and, in the remaining 355, the relapse was confined to the pelvis. There were 290 men and 229 women whose age ranged from 23 to 91 years (median = 65). Median time from initial surgery to radiation therapy for local recurrence was 18 months (3-138 months). Radiation therapy was given with varying dose-fractionation schedules, total doses ranging from 4.4 to 65.0 Gy (median = 30 Gy) over 1 to 92 days (median = 22 days). For 214 patients who received a total dose > or = 35 Gy, radiation therapy was given in 1.8 to 2.5 Gy daily fractions. RESULTS: The median survival was 14 months and the median time to local disease progression was 5 months from date of pelvic irradiation. The 5-year survival was 5%, and the pelvic disease progression-free rate was 7%. Twelve patients remained alive and free of disease at 5 years after pelvic irradiation. Upon multivariate analysis, overall survival was positively correlated with ECOG performance status (p = 0.0001), absence of extrapelvic metastases (p = 0.0001), long intervals from initial surgery to radiation therapy for local recurrence (p = 0.0001), total radiation dose (p = 0.0001), and absence of obstructive uropathy (p = 0.0013). Pelvic disease progression-free rates were positively correlated with ECOG performance status (p = 0.0001), total radiation dose (p = 0.0001), and previous conservative surgery for the primary (p = 0.02). CONCLUSIONS: Survival is poor for patients who develop local recurrence following previous surgery for rectal carcinoma. Pelvic radiation therapy provides only short-term palliation, and future efforts should be directed to the use of effective adjuvant therapy for patients with rectal carcinoma who are at high risk of local recurrence.     

Continuous hyperfractionated accelerated radiotherapy with/without mitomycin C in head and neck cancer

PURPOSE: To evaluate the effect of mitomycin C to an accelerated hyperfractionated radiation therapy. The aim was to test a very short schedule with/without mitomycin C (MMC) with conventional fractionation in histologically verified squamous cell carcinoma of the head and neck region. METHODS AND MATERIALS: From October 1990 to December 1996, 188 patients entered the trial. Tumors originated in the oral cavity in 54, oropharynx in 82, larynx in 20, and hypopharynx in 32 cases, respectively. Patients' stages were predominantly T3 and T4 (158/188, 84%) and most patients had lymph node metastases (144/188, 77%) at diagnosis. Only 22 patients were female, 166 were male, the median age of patients was 57 years (range 34 to 76 years). Patients were randomized to one of the following three treatment options: conventional fractionation (CF) consisting of 70 Gy in 35 fractions over 7 weeks (65 patients) or continuous hyperfractionated accelerated radiation therapy (V-CHART; 62 patients) or continuous hyperfractionated accelerated radiation therapy with 20 mg/sqm MMC on day 5 (V-CHART + MMC; 61 patients). By the accelerated regimens, the total dose of 55.3 Gy was delivered within 17 consecutive days, by 33 fractions. On day 1, a single dose of 2.5 Gy was given, from day 2 to 17 a dose of 1.65 Gy was delivered twice: the interfraction interval was 6 hours or more. RESULTS: Mucositis was very intense after accelerated therapy, most patients experiencing a grade III/IV reaction. The mucosal reaction did not differ whether MMC was administered or not. Patients treated by accelerated fractionation experienced a confluent mucosal reaction 12-14 days following start of therapy and recovered (no reaction) within 6 weeks. The skin reaction was not considered different in the three treatment groups. Those patients treated with additional chemotherapy experienced a grade III/IV hematologic toxicity in 12/61 patients. Initial complete response (CR) was recorded in 43% following CF, 58% after V-CHART, and 67% after V-CHART + MMC, respectively (p < 0.05). Actuarial survival (Kaplan-Meier) was significantly improved in the combined treated patients. Local tumor control was 28%, 32%, and 56% following CF, V-CHART, and V-CHART + MMC, respectively (p < 0.05). CONCLUSION: We conclude that our continuous hyperfractionated accelerated radiation therapy regimen is equal to conventional fractionation, suggesting that by shortening the overall treatment time from 7 weeks to 17 days a reduction in dose from 70 Gy to 55.3 Gy is possible, with maintenance of local tumor control rates. The administration of MMC to the accelerated regimen is tolerable and improves the outcome for patients significantly.     

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.     

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.     

Genetics of male infertility

This study was undertaken to analyze the influence of total skin dose and dose-fractionation schedules on the response rate, survival and skin toxicity of patients with mycosis fungoides [MF] treated with total skin electron irradiation [TSEI]. From 1979 to 1992, 40 patients with MF were treated with TSEI using a modified Christie Hospital technique. Mean follow-up time was 48 months [median 20 months]. 37/40 patients completed TSEI; three died due to non-treatment-related conditions during therapy. 34/37 [92%] treated patients achieved complete remission [CR] and 16/40 [40%] are alive with no evidence of disease. Over the years, changes in dose-fractionation schedules were made and correlated with the pattern of CR and skin toxicity. The 5-year actuarial survival [Stanford staging] was 84% in Stages IA-IB [all Stage IA patients are alive] and 59% in Stage II. The probability of survival of Stage III-IV patients was 30% at 30 months. Late skin toxicity was mild to moderate in 60% and severe in 25% of patients. A reduction of the total dose and dose-per-fraction resulted in an acceptable CR rate and a significantly lower toxicity. TSEI is effective in early stage MF. Skin control and late skin toxicity seem to be dose-fractionation-schedule related. For the early stages, the optimal treatment schedule seems to be 24-30 Gy to the whole skin surface in 2.4-3.0 Gy fractions, given twice weekly over a period of four to six weeks. Total doses of 24-30 Gy at 2.4-3.0 Gy per fraction yielded comparable skin control rates with lower skin toxicity.     

Results of high-dose thoracic irradiation incorporating beam's eye view display in non-small cell lung cancer: a retrospective multivariate analysis

PURPOSE: To review the University of Michigan clinical experience in nonsmall cell lung cancer using high-dose thoracic irradiation (> or = 60 Gy) so that a starting dose for our prospective dose-escalation study could be determined. METHODS AND MATERIALS: Eighty-eight consecutive patients diagnosed with medically inoperable or locally advanced, unresectable nonsmall cell lung cancer were identified who were treated with thoracic irradiation alone to a minimum total dose of 60 Gy (uncorrected for lung density). All patients except four (95%) underwent computed tomography scanning for treatment planning that included beam's eye view display for tumor and critical structure localization. All patients were treated with standard fractionation in a continuous course to uncorrected total doses ranging from 60 to 74 Gy (median, 67.6 Gy). RESULTS: The median follow-up exceeds 24 months for all surviving patients (range, 12 to 78 months). The median survival time was 15 months, and the 2- and 3-year overall actuarial survival rates were 37% and 15%, respectively. Survival was significantly different between stage of disease (p = .004) and N-stage (p = .002) by univariate analysis. In a multivariate analysis, stage becomes the only characteristic significantly associated with outcome. The median time to local progression for 86 evaluable patients was 29 months. Stage (p = .0003), T-stage (p = .0095) and N-stage (p = .027) were significantly different with respect to local progression-free survival by univariate analysis. However, only stage was prognostic for local progression-free survival by multivariate analysis. There was no difference between large volume treatment (inclusion of the contralateral hilar and supraclavicular lymph nodes) and small volume treatment (exclusion of these elective nodal sites) with respect to local progression-free survival (p = .507) or survival (p = .520). With regard to dose, there was no significant difference between patients who received > 67.6 Gy and patients who received < or = 67.6 Gy with respect to local progression-free survival (p = .094) or survival (p = .142). Within the Stage III subgroup, local progression-free survival (p = .018) and survival (p = .061) were longer favoring the high-dose group of patients. Despite these doses, disease progression within the irradiated field was the predominant first site of treatment failure. CONCLUSION: This retrospective study has shown that it is feasible to deliver uncorrected tumor doses as high as 70 Gy using standard fractionation in NSCLC with acceptable morbidity. Local control remains a significant problem. These data indicate justification for a starting dose in a prospective radiation dose-escalation study.