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.     

Molecular analysis of Plasmodium vivax relapses using the MSP1 molecule as a genetic marker

PURPOSE: To evaluate radiation therapy regimens for improvement in local control in patients with limited-stage small cell lung cancer. MATERIALS AND METHODS: Radical radiation therapy results in 117 patients with limited-stage small cell lung cancer were retrospectively reviewed. The protocols in 90 patients were 40 Gy in 20 fractions (n = 28), 50 Gy in 25 fractions (n = 32), and 45 Gy in 30 fractions (accelerated hyperfractionation, n = 30). The other 27 patients received thoracic irradiation (dose range, 20-60 Gy; median dose, 54 Gy). All patients underwent systemic chemotherapy. RESULTS: The 5-year Kaplan-Meier survival rates in the patients with N0, N1, N2, and N3 disease were 26%, 34%, 18%, and 0%, respectively; the rates of in-field relapse were 25%, 36%, 26%, and 25%, respectively; and the rates of marginal relapse were 0%, 9%, 15%, and 29%, respectively. In 56% of patients with marginal relapse, the relapse site was at the upper margin. The 4-year in-field control rates for the patients who underwent 40, 50, and 45 Gy were 51%, 70%, and 56%, respectively. CONCLUSION: Patients with N3 limited-stage small cell lung cancer should undergo a separate protocol, and the upper margin should be extended in patients with N2 or N3 disease.     

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.     

Soft tissue sarcomas

Soft tissue sarcomas are relatively rare tumors with an annual incidence of 5000 to 6000 in the United States. The primary therapy is surgical resection with an adequate margin of normal tissue. For patients at high risk local control is improved with postoperative adjuvant radiation. Local recurrence rates vary depending on the anatomic site. In extremity lesions one third of patients will have locally recurrent disease with a median disease-free interval of 18 months. Treatment results for extremity local recurrence may approach those for primary disease. Isolated pulmonary metastases may be resected with 20% to 30% 3-year survival rates. Patients with sarcomas in other sites present similar but more difficult problems in terms of local control and management of disseminated disease. Patients with unresectable pulmonary metastases or extrapulmonary metastatic sarcoma have a uniformly poor prognosis and are best treated with systemic chemotherapy.     

Arnold-Chiari malformation in a captive African lion cub

PURPOSE: Surgery and systemic chemotherapy offer modest benefit to patients with recurrent glioblastoma multiforme. These tumors are associated with rapid growth and progressive neurological deterioration. Radiosurgery offers a rational alternative treatment, delivering intensive local therapy. A pilot protocol to treat recurrent glioblastoma was developed using fractionated stereotactic radiosurgery with concurrent intravenous (i.v.) Taxol as a radiation sensitizer. METHODS AND MATERIALS: The treatment outcome was analyzed in 14 patients with recurrent glioblastoma treated with fractionated stereotactic radiosurgery and concurrent Taxol. Median tumor volume was 15.7 cc and patients received a mean radiation dose of 6.2 Gy at 90% isodose line, 4 times weekly. The median dose of Taxol was 120 mg/m2. RESULTS: The median survival was 14.2 months, 1-year survival was 50%. CONCLUSIONS: Survival for this small group of patients was similar to or better than historical controls or patients treated with single-fraction radiosurgery alone. This data should stimulate the investigation of both fractionated radiosurgery and the development of radiation sensitizers to further enhance treatment.     

Diagnostic imaging 100 years ago

The aim of the present study was the evaluation of the role of adjuvant radiation therapy in the prevention of recurrence after excision. Between July 1, 1985, and April 1, 1993, 64 patients (43 men, 21 women) were referred for radiation therapy after excision of a nasal pterygium. All patients were followed for 1-9 years (median 5.5 years). Radiation therapy was done with a strontium 90 eye applicator at a total dose of 30 Gy fractionated into six fractions of 5 Gy each. In all, 49 patients were treated after their first excision and 15 patients had undergone multiple prior excisions. In 8 of 64 irradiated patients, recurrent pterygium was detected (12.5%); 4 recurrences developed after first excision and adjuvant radiation therapy (8.16%) and the other 4, following multiple former reexcisions and radiotherapy (26.7%). Pterygium did not recur in any of the primarily treated patients who were irradiated within 3 days of surgery. In contrast, 3 of 7 accordingly treated patients (42.9%) who started radiation therapy at between 7 and 10 days after surgery developed recurrent pterygium. Adjuvant radiation therapy after excision of pterygium lowers the overall rate of recurrence to 12.5%. In an adjuvant situation after first excision, radiation therapy should be initiated within 3 days of surgery, the result being freedom from recurrence.     

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.     

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.     

Supratentorial malignant gliomas in childhood: a single institution perspective

BACKGROUND: A retrospective study evaluated the clinical characteristics, prognostic factors, and outcome of patients with newly diagnosed supratentorial malignant gliomas treated with preirradiation chemotherapy. METHODS: Of 41 patients with supratentorial malignant gliomas accrued between 1984-1994, all had neuroimaging documentation of the extent of resection and 37 had complete neuraxis staging prior to treatment; 80% were treated with one of a variety of neoadjuvant chemotherapy regimens. RESULTS: Thirteen patients had anaplastic astrocytoma (AA), 25 had glioblastoma multiforme (GBM), and 3 had anaplastic oligodendroglioma. Gross total resection (GTR) was performed in 10 patients, subtotal resection (STR) in 22 patients, and biopsy (Bx) alone in 9 patients. For the entire group the 3-year overall and progression free survivals were 35 +/- 8% and 18 +/- 6%, respectively. Tumor recurrence was dominantly local. However, 9 patients with initially local disease failed at a distant neuraxis site, giving a 26 +/- 7% actuarial risk of dissemination at 3 years. The only significant prognostic factor was extent of tumor resection: patients who underwent GTR survived longer than those who underwent STR or Bx (P = 0.004). Histology (GBM vs. AA), age, and the use of enhanced local dose radiation therapy (brachytherapy or stereotactic irradiation) did not affect survival. CONCLUSIONS: Neoadjuvant chemotherapy was not associated with a survival rate significantly different from that observed in adjuvant chemotherapy studies. Systematic neuraxis staging at diagnosis and recurrence revealed a rate of neuraxis dissemination as a component of recurrence that was higher than previously reported; the utility of craniospinal irradiation in preventing isolated dissemination remains uncertain.     

Use of concurrent chemotherapy, accelerated fractionation radiation, and surgery for patients with esophageal carcinoma

BACKGROUND: The results of a Phase II study of concurrent chemotherapy and accelerated fractionation radiation therapy followed by surgical resection for patients with both adenocarcinoma and squamous cell carcinoma of the esophagus are presented. Pretreatment and postinduction staging were correlated with pathologic findings at surgery to assess the role of surgical resection and the predictive value of noninvasive staging techniques. METHODS: Patients received 2 induction courses with 4-day continuous intravenous infusions of cisplatin (20 mg/m2/day) and 5-fluorouracil (1000 mg/m2/day) beginning on Day 1 and Day 21, concurrent with a split course of accelerated fractionation radiation (1.5 grays [Gy] twice daily, to a total dose of 45 Gy). All patients were subsequently referred for surgical resection. A single, identical postoperative course of chemotherapy and 24 Gy accelerated fractionation radiation was planned for patients with residual tumor at surgery. RESULTS: Seventy-four patients were entered on this study; 72 patients were considered eligible and evaluable. Induction toxicity included nausea (85%), increased dysphagia (90%), neutropenia (<1000/mm3) (43%), thrombocytopenia (<20,000/mm3) (10%), and reversible nephrotoxicity (8%). Sixty-seven patients (93%) underwent surgery, and 65 (90%) were found to have resectable tumors. Twelve of these patients (18%) died perioperatively, and 18 (27%) had no residual pathologic evidence of disease. Resolution of symptoms and normalization of radiographic studies, endoscopy, or esophageal ultrasound did not identify pathologic complete responders accurately. No patient completing induction therapy and surgery experienced a locoregional recurrence. The Kaplan-Meier 4-year projected recurrence free and overall survival rates were 49% and 44%, respectively. CONCLUSIONS: Although this regimen is feasible, there was significant preoperative toxicity and perioperative mortality. Nonetheless, the recurrence free and overall survival rates were encouraging. However, no staging tool can predict a pathologic complete response after induction therapy accurately, suggesting a continued need for surgical resection.     

Analysis of prognostic factors in localized gastric lymphoma: the importance of bulk of disease

PURPOSE: To identify prognostic factors in localized gastric lymphoma patients for optimal therapy selection. METHODS AND MATERIALS: From 1974 to 1990, 77 patients with localized gastric lymphoma (38 Stage IE and 39 Stage IIE) were treated with radiation therapy, chemotherapy, surgery, or a combination. Univariate and multivariate local control and survival analyses were performed on possible prognostic factors, such as patient age, gender, histologic subtype, stage, tumor size, depth of penetration, multicentricity, and treatment modality. RESULTS: At 5 years, the relapse-free survival was 52%; 74% of the relapses occurred at local sites. Smaller tumor size was most strongly associated with local control (p = .001) and relapse-free survival (p < .001). Patients with tumor sizes < or = 5 cm had relapse-free survival of 87%, compared with 41% and 15% for those with tumor sizes of 5.1 cm to 10 cm and > 10 cm, respectively. The 47 patients who received combined-modality therapy had a relapse-free survival of 65%, compared with 24% for the 30 who received single-modality therapy (p < .01). Although patient age, stage, depth of penetration, and resective surgery affected the above endpoints, these factors were not independent predictors of outcome. Analysis of treatment subgroups showed that surgical resection combined with postoperative irradiation was associated with highest local control (p = .002) and the best relapse-free survival (p = .004), when compared with other treatment modalities. In 27 patients with tumor sizes < or = 5 cm, comparison of the 15 patients who had surgery with the 12 who did not failed to reveal a local control benefit from the addition of surgery. CONCLUSION: These data demonstrate that tumor bulk is an important prognostic determinant of local control and relapse-free survival in localized gastric lymphoma patients. Stage IE and IIE lymphoma of the stomach can be selectively treated with primary radiation, but surgical resection may be necessary for large tumors (> 5 cm), followed by adjuvant radiation.     

Effect of rodents on reforestation in the moumtain regions near Beijing

A long survival is rarely observed in patients demonstrating recurrent malignant lymphoma with bulky disease because of the appearance of chemoresistant tumor cells after extensive chemotherapy, and moreover the presence of bulky disease has also been consistently associated with a poorer response rate and a shortened survival, due to the fact that tumor size is the most significant factor for the treatment of non-Hodgkin's lymphoma. We herein describe a case of a 53-year-old woman presenting with the chief complaint of abdominal fullness, who underwent intraoperative radiation therapy (IORT) for recurrent bulky non-Hodgkin's lymphoma in the mesenterium. The patient has had no evidence of tumor recurrence, based on the findings of regular abdominal computed tomographic scans, 60 months after initial chemotherapy and 28 months after IORT.     

Results of conservative surgery and radiation for mammographically detected ductal carcinoma in situ (DCIS)

PURPOSE: The role of conservative surgery and radiation for mammographically detected ductal carcinoma in situ (DCIS) is controversial. In particular, there is little data for outcome with radiation in a group of patients comparable to those treated with local excision and surveillance (mammographic calcifications < or = 2.5 cm, negative resection margins, negative postbiopsy mammogram). This study reports outcome of conservative surgery and radiation for mammographically detected DCIS with an emphasis on results in patients considered candidates for excision alone. METHODS AND MATERIALS: From 1983 to 1992, 110 women with mammographically detected DCIS (77% calcifications +/- mass) and no prior history of breast cancer underwent needle localization and biopsy with (55%) or without a reexcision and radiation. Final margins of resection were negative in 62%, positive 7%, close 11%, and unknown 20%. The median patient age was 56 years. The most common histologic subtype was comedo (54%), followed by cribriform (22%). The median pathologic tumor size was 8 mm (range 2 mm to 5 cm). Forty-seven percent of patients with calcifications only had a negative postbiopsy mammogram prior to radiation. Radiation consisted of treatment to the entire breast (median 50.00 Gy) and a boost to the primary site (97%) for a median total dose of 60.40 Gy. RESULTS: With a median follow-up of 5.3 years, three patients developed a recurrence in the treated breast. The median interval to recurrence was 8.8 years and all were invasive cancers. Two (67%) occurred outside the initial quadrant. The 5- and 10-year actuarial rates of recurrence were 1 and 15%. Cause-specific survival was 100% at 5 and 10 years. Contralateral breast cancer developed in two patients. There were too few failures for statistical significance to be achieved with any of the following factors: patient age, family history, race, mammographic findings, location primary, pathologic size, histologic subtype, reexcision, or final margin status. However, young age, positive or close margins, and the presence of a mass without calcifications had a trend for an increased risk of recurrence. There were no recurrences in the subset of 16 patients who would be candidates for surveillance by Lagios' criteria. CONCLUSION: For selected patients, conservative surgery and radiation for mammographically detected DCIS results in a low risk of recurrence in the treated breast and 100% 5- and 10-year cause-specific survival. Improved mammographic and pathologic evaluation results in better patient selection and reduces the risk of the subsequent appearance of DCIS in the biopsy site. The identification of risk factors for an ipsilateral invasive breast recurrence is evolving.     

The long-term results of pre-operative hyperthermo-chemo-radiotherapy for oesophageal carcinoma--a comparison with preoperative radiation therapy alone

The long-term results of patients with oesophageal carcinoma treated with pre-operative hyperthermo-chemo-radiotherapy (HCR) and pre-operative radiation therapy alone were compared. Twenty-six patients treated with pre-operative hyperthermo-chemo-radiotherapy (HCR Group) and 25 treated with radiation therapy alone (R Group), which demonstrated histopathologically marked effective results (Grade 3), were entered into the study. The 3-year survival rates after oesophagectomy in the HCR Group and the R Group were 67.4% and 41.8%, respectively, while the 5-year survival rates were 50.5% and 34.9%, respectively. Thus post-operative prognosis in the HCR Group was significantly more favourable than that in the R Group (P < 0.05). The local recurrence and distant metastasis rate in the HCR Group was significantly less than in the R Group (P < 0.01). This significant difference in prognosis was thought to be due to the reinforced effects of local regulation by hyperthermia and the systemic control of micrometastasis by chemotherapy in addition to radiation. Our data suggest that for carcinoma of oesophagus, pre-operative hyperthermo-chemo-radiotherapy contributes to prolonged post-operative survival while reducing both local recurrence and micrometastasis.     

Accelerated-interrupted radiation therapy given concurrently with chemotherapy for locally advanced non-small cell lung cancer

PURPOSE: To evaluate the efficacy of multidrug chemotherapy combined with accelerated radiation therapy in the treatment of localized but unresectable non-small cell lung cancer. PATIENTS AND METHODS: Between September 1990 and February 1993, 35 patients with Stage III (15 IIIA & 20 IIIB) non-small cell lung cancer were entered on a protocol using combined accelerated radiation therapy and chemotherapy. Radiation therapy consisted of 55.6 Gy in 30 fractions (1.8 Gy bid for 5 consecutive days given in 3 weeks [total of 15 days], every other week). Chemotherapy consisted of cisplatin (10 mg/m2), vinblastine (4 mg/m2), 6-thioguanine (40 mg bid), and 5-fluorouracil (400 mg/m2 as continuous infusion) given concomitantly with radiation therapy. Approximately 3 weeks following completion of radiation therapy, two cycles of consolidation chemotherapy were given, consisting of two doses of cisplatin (120 mg/m2) 4 weeks apart and six doses of vinblastine (4 mg/m2) given on two consecutive days every other week for 3 weeks. RESULTS: Six patients were still alive at last follow-up; for them the median follow-up time is 47 months (range, 39-55.8). The median survival time is 17.5 months. The 1-, 2-, 3- and 4.5-year survival rates are 69%, 37%, 20% and 17%, respectively. Overall response rate is 63%, with 51.5% partial response and 11.5% complete response rates. Esophagitis occurred as follows: Grade 4 = 0, Grade 3 = 1, Grade 2 = 6, and Grade 1 = 13. No patient developed Grade 3 or 4 acute respiratory toxicity. Significant hematologic toxicity occurred as follows: 37% Grade 3 and 31% Grade 4 leukopenia. Radiation pneumonitis occurred in two patients. DISCUSSION: The regimen tested in this protocol appears to be very well tolerated with minimal pulmonary or esophageal toxicity. This, coupled with the shortened course of radiation therapy and the ability to deliver the combined radiation and chemotherapy portion of the treatment on an outpatient basis most of the time, has made multi-modality treatment for this malignancy much easier and more convenient for patients. In addition, the favorable survival in this group of patients with locally advanced disease is very encouraging and warrants further study.     

Long-term results of preoperative radiation therapy alone for stage T3 and T4 rectal cancer

BACKGROUND: There has been a resurgence of interest in the use of preoperative radiation therapy, with or without chemotherapy, for locally advanced rectal cancer. The purpose of this study was to analyse the time course and pattern of failure for 74 patients with clinical stage T3 or T4 (cT3-4) rectal cancer treated with preoperative radiation therapy for whom long-term follow-up was available. METHODS: Seventy-four patients with cT3-4 rectal cancer received a median of 45.0 Gy radiation alone followed by surgery 4-8 weeks later. Median follow-up was 90 months; two-thirds of patients were followed for at least 60 months. RESULTS: Following radiation therapy the pathological stage was 4 per cent pT0, 26 per cent pT1-2 and 70 per cent pT3-4. Thirty-two per cent had involved lymph nodes. The actuarial 5-year rates of local control, freedom from distant metastasis and disease-specific survival were 80, 64 and 73 per cent respectively. The corresponding 10-year rates were 73, 51 and 50 per cent. Median times to detection of local and distant recurrence were 34 and 24 months respectively. Eighty per cent of local recurrences were detected within 54 months; 80 per cent of distant recurrences were detected within 57 months. CONCLUSION: In this analysis, the time to detection of both local and distant recurrences following preoperative radiation therapy for advanced rectal cancer was surprisingly long. Almost 5 years (57 months) of follow-up were required to detect 80 per cent of all failures. The 5-year local control rate of 80 per cent compares favourably with that achieved by more aggressive chemoradiation regimens for fixed cancers; however, the high distant failure rate with radiation therapy alone suggests that adjuvant systemic therapy should be investigated.     

Value of postoperative radiotherapy in malignant tumors of the upper urinary tract. Apropos of a series of 26 patients

To evaluate the role of adjuvant radiation therapy in invasive transitional cell carcinoma of the upper urinary tract, we retrospectively reviewed a series of 26 patients who underwent radical surgery plus post-operative prophylactic irradiation for such a tumor. Between 1980 and October 1993, 18 men and eight women (mean age: 65 +/- 9 years) were treated for an invasive transitional cell carcinoma of the upper urinary tract. Tumor location was the renal pelvis in 15 patients (58%). The tumor was pathological stage B in 11 patients (42%) and stage C in 15 patients (58%). Tumor grade was 2 in ten patients, 3 in 15 and unknown in one. Nine patients had node involvement. All patients underwent surgery followed by radiation therapy to a total dose of 45 Gy to the tumor bed (23 patients) and/or regional nodes (18 patients). After a mean follow-up of 45 months, 13 patients (50%) were alive and 11 were disease-free. Local tumor relapse, nodal recurrence, metastasis and second urothelial location were noted in one, four (15%), 14 (54%) and eight patients (30%) respectively. Overall 5-year survival and 5-year disease-free survival were 49% and 30% respectively. Overall 5-year survival rates were 60% for stage B and 19% for stage C disease (P = 0.07), 43% for node-negative versus 15% for node-positive cancer (P = 0.04) and 90% for grade 2 and 0% for grade 3 tumors (P < 0.01). In this study using a radio-surgical approach, local control of disease and survival were similar to those reported previously in surgical series. Prophylactic post-operative radiation therapy is not recommended.     

Treatment of stage IE primary lymphoma of bone

PURPOSE: A retrospective analysis was performed to assess the efficacy of various treatments of Stage IE primary non-Hodgkins lymphoma of bone. METHODS AND MATERIALS: Sixty-three patients with Stage IE primary non-Hodgkins lymphoma of bone (single osseous focus) were seen at our institution between the years 1970 and 1989. Information was obtained regarding each patients' presentation and clinical course. The histology was reviewed in all patients. Modern immunohistochemical stains were performed on each case with available paraffin-embedded tissue. RESULTS: The histologic classification of the tumors was as follows: 43 diffuse large cell, 13 diffuse mixed cell, 3 small noncleaved, and 4 unclassified. The most common presenting symptom was pain (97%) and the following bony sites were involved: 36 long bone, 9 flat bone, 13 spine, and 5 pelvis. Of the 63 cases, 50 were treated with radiation alone, 10 with chemotherapy and radiation, 2 with chemotherapy alone, and 1 with surgery alone. Univariate analysis revealed a suggestion of an improved 5-year disease-free survival for patients treated with chemotherapy and radiation vs. radiation alone (90% vs. 57% respectively, p = .08). Multivariate analysis (controlling for extent of initial evaluation, extent of pathological evaluation and other potential prognostic factors) showed that neither treatment resulted in superior outcome with respect to disease-free survival, disease specific survival, or overall survival, however, doses of radiation greater than 4000 cGy resulted in improved overall survival compared to lower doses (p = 0.01). CONCLUSION: This study supports the use of primary RT (> 4000 cGy) for Stage IE PLB, however, the addition of chemotherapy to the radiotherapeutic management may decrease the initial relapse rate of some patients. Future studies should address this question.     

Resection of metastatic renal cell carcinoma

PURPOSE: Resection of solitary metastases from renal cell carcinoma (RCC) is associated with a 5-year survival rate of 35% to 50%. Selection criteria are not well defined. PATIENTS AND METHODS: We retrospectively analyzed our experience with 278 patients with recurrent RCC from 1980 to 1993. RESULTS: One hundred forty-one of 278 patients underwent a curative metastectomy for their first recurrence (44% 5-year overall survival [OS] rate), 70 patients underwent noncurative surgery (14% 5-year OS rate), and 67 patients were treated nonsurgically (11% 5-year OS rate). Favorable features for survival were a disease-free interval (DFI) greater than 12 months versus 12 months or less (55% v 9% 5-year OS rate; P < .0001), solitary versus multiple sites of metastases (54% v 29% 5-year OS rate; P < .001), and age younger than 60 years (49% v 35% 5-year OS rate; P < .05). Among 94 patients with a solitary metastasis, lung (n = 50; 54% 5-year OS rate) was more favorable than brain (n = 11; 18% 5-year OS rate; P < .05). Survival rates after curative resection of second and third metastases were not different compared with initial metastectomy (46% and 44%, respectively, v 43% 5-year OS rates; P = nonsignificant). Favorable predictors of survival by multivariate analysis included a single site of first recurrence, curative resection of first metastasis, a long DFI, a solitary site of first metastasis, and a metachronous presentation with recurrence. CONCLUSION: Selected patients with recurrent RCC who can undergo a curative resection of their disease have a good opportunity for long-term survival, particularly those with a single site of recurrence and/or a long DFI.     

Radiotherapy and local control in rectal cancer

Recurrence is a stage in the natural history of rectal cancer. Preoperative radiotherapy or postoperative radiochemotherapy lower the rate of recurrence, improving local control. From 1980 to 1997, at the "Divisione di Radioterapia" of the "Università Cattolica del S. Cuore" of Rome 380 patients with rectal cancer of early clinical stage T2-3, candidates for surgery for cure, underwent radiation therapy. 119 patients underwent postoperative radiotherapy (45-50 Gy); 45 patients underwent "sandwich" radiotherapy (45 Gy:27 Gy before and 28 Gy after surgery), of whom 7 were treated with preoperative radiotherapy alone; 145 patients underwent preoperative concomitant radiochemotherapy according to 3 different protocols, radiotherapy (38 Gy) combined with mitomycin C and 5-FU; radiotherapy (50.4 Gy) combined with cisplatin and 5-FU; radiotherapy (45 Gy) combined with 5-FU and folinic acid. 71 patients were treated with preoperative radiotherapy (38 Gy) combined with IORT (10 Gy). Median follow-up was 6 years. Overall local control was 85% at 3 years, 83% at 5 years, 81% at 10 years. The rate of local control at 5 years was: 76% for postoperative radiotherapy, 83% for "sandwich" radiotherapy, 84% for preoperative radiochemotherapy and 93% for preoperative radiotherapy combined with IORT. Local control was shown to be significantly better with preoperative treatment as compared to postoperative treatment (p = 0.02). The incidence of metastases was 35% in the patients with local recurrence and 16% in those with local control. The difference in survival was highly significant in patients with local control as compared to those with local recurrence: at 5 years 87% and 32% respectively. Patients with local control showed a lower incidence of metastasis and a better survival.