Partial breast irradiation with interstitial high-dose-rate brachytherapy in early breast cancer: results of a phase II prospective study.

AIM: To investigate, in a phase II prospective study, the efficacy of partial breast irradiation administered with high-dose-rate brachytherapy. METHODS: After conservative surgery 80 patients with low-risk early-stage breast cancer received 4 Gy twice a day for 4 days (total dose 32 Gy). Catheter implantation was performed during surgery in 15 cases and postoperatively, at a median of 8 weeks from surgery, in 65 patients. Adjuvant therapy was chemotherapy (8) and/or hormone therapy (61). RESULTS: Cosmetic results were good/excellent in 79 patients. Perioperative toxicity was very low. Acute skin toxicity developed in seven cases (six G1; one G2); late G3 cutaneous toxicity in one patient and late subcutaneous toxicity in five (three G1; two G2). Grade 1 teleangiectasia occurred in eight patients and grade 2 in one. Fat necrosis was symptomatic in one patient and asymptomatic in five. Only one patient presented pain after brachytherapy. A significantly (p=0.001) higher frequency of late toxicity was observed in patients implanted during surgery, the group, which included the only patient with a fair cosmetic result. No local or regional relapses have occurred to date. The median follow-up was 30 months (range 3-52). CONCLUSION: This strategy is a viable option in selected patients with early-stage breast cancer as it is feasible, reproducible and associated with very low perioperative and acute toxicity. The low incidence of late side effects will probably change as follow-up lengthens.

Cataracts in patients receiving stem cell transplantation after conditioning with total body irradiation.

One hundred and ninety-three patients with hematological malignancies and a follow-up > or =1 year, treated with stem cell transplantation (45 autologous, 99 allogeneic T cell-depleted matched, 49 allogeneic T cell-depleted mismatched) from July 1985 to May 1998, were considered evaluable for the development of cataracts. Total body irradiation (TBI), administered either according to a hyperfractionated scheme (HTBI) or in a single dose (STBI), was employed in the conditioning regimens. HTBI was prescribed in 94% of patients undergoing allogeneic matched transplant, while STBI was used in 71% of patients receiving allogeneic mismatched and in all patients undergoing autologous transplant. The median follow-up was 7.56 years in the HTBI and 3.02 years in the STBI group. Among the different risk factors analyzed by univariate analysis only the TBI scheme and type of transplant reached statistical significance (P < 0.0001 and P < 0.001, respectively). By multivariate analysis only the TBI scheme was an independent factor for cataract development (STBI vs HTBI RR 7.2; P < 0.01). Our results showed that STBI is more cataractogenic than HTBI. The incidence of cataract we observed was among the lowest described in the literature. T cell depletion, because it prevents graft-versus-host disease and reduces the protracted use of post-transplant steroids, explains the results we obtained.

Adjuvant radiochemotherapy in high-risk rectal cancer results of a prospective non-randomized study.

AIMS AND BACKGROUND: In 1990 the National Institutes of Health Consensus Conference recommended adjuvant combined therapy for patients with radically resected rectal cancer at high risk for relapse (ie, stage II-III). The purpose of our prospective non-randomized study was to verify the feasibility and effectiveness of postoperative radiochemotherapy in terms of improvement in disease-free and overall survival in this patient subgroup. STUDY DESIGN: From January 1990 to October 1998, 191 consecutive patients with radically resected stage II-III rectal cancer were treated. A total of 159 patients with a 24-month follow-up were assessable for toxicity and survival. Anterior resection was performed in 129 (81%) and abdomino-perineal resection in 30 (19%) patients. Fifty-four (34%) stage II and 105 (66%) stage III patients entered the study. Within 45-60 days of surgery, all patients received 5-fluorouracil chemotherapy at the dose of 500 mg/m2 as an i.v. bolus on days 1-5, every 4 weeks, for 6 cycles. Chemotherapy cycles III and IV were administered at the same daily dose on radiotherapy days 1-3 and 29-31. Radiotherapy consisted of 45 Gy/25 fractions plus a boost dose of 5.4 Gy. RESULTS: After a median follow-up of 57 months (range, 25-123), overall recurrent disease was reported in 58 (36%) patients: local, systemic, and both local and systemic relapses in 12 (8%), 37 (23%) and 9 (6%) cases, respectively. According to local extension, recurrence rates were 15% and 48% in stage II and III, respectively. Five-year overall and disease-free survival were 71% and 66%, respectively. Overall survival was 87% in stage II and 62% in stage III patients, and disease-free survival was 84% and 56% in stage II and III disease, respectively. According to univariate and multivariate analyses, significant prognostic factors for better tumor control were: stage (II vs III, P <0.001), the number of involved nodes (< or = 3 vs > 3, P <0.0001), and no extracapsular node invasion (P <0.0001). The recommended dose of the combined radiochemotherapy regimen was generally well tolerated. The incidence of any > or = grade 3 acute toxicity (according to the WHO scale) was 13% diarrhea, 11% proctitis, 5% perineal dermatitis and 4% myelosuppression. Four (3%) patients had radiotherapy-related severe late toxicity which required surgery. CONCLUSIONS: The study provided recurrence rates and survival similar to other adjuvant radiochemotherapy regimens published in the literature. However, in view of the low 5-year survival rate recorded in stage III patients, a different approach should be investigated.

Results of a prospective study with high-dose etoposide, thiotepa and carboplatin and peripheral blood stem cell rescue for high-risk stage II-IIIA and selected stage IV breast cancer patients.

AIMS AND BACKGROUND: To investigate the safety and efficacy of a high-dose chemotherapy regimen with etoposide, carboplatin and thiotepa in high-risk stage II-IIIA breast cancer and in responsive metastatic patients. STUDY DESIGN: From April 1992 to December 1998, 24 patients with high-risk stage II-IIIA breast cancer (> or = 9 positive nodes) and 9 responsive metastatic patients were enrolled in the trial. After induction chemotherapy with an anthracycline-based regimen, peripheral blood stem cells were mobilized with cyclophosphamide (7 g/m2) and G-CSF (5-16 microg/kg/s.c./day). The high-dose chemotherapy regimen consisted of etoposide (1000 mg/m2), carboplatin (800 mg/m2) and thiotepa (500 mg/m2). At the end of the high-dose chemotherapy, all stage II-IIIA patients received radiotherapy to the breast or chest wall and draining nodes; stage IV patients were irradiated to sites of disease, if feasible. All ER+ and/or PgR+ patients were treated with hormone therapy. RESULTS: For stage II-IIIA high-risk patients, the median follow-up was 4.36 years (range, 1.93-6.94), and the Kaplan-Meier estimate at 5 years of disease-free survival and overall survival was 54.8 +/- 11% SE and 76.73 +/- 9.4% SE, respectively. For metastatic patients, the median follow-up was 4.93 years (range, 4.15-7.95), and the Kaplan-Meier estimate at 5 years of progression-free survival and overall survival was 22.2 +/- 13.9% SE and 76.2 +/- 14.8% SE, respectively. No treatment-related deaths were observed. CONCLUSIONS: Our results are comparable to those obtained in other high-dose chemotherapy trials but do not seem to be superior to conventional-dose therapy given to similar patients.

Evaluation of level I and II axillary nodes included in the standard breast tangential fields and calculation of the administered dose: results of a prospective study.

PURPOSE: To evaluate if Level I and II axillary nodes are included in the standard breast tangential fields, and to calculate the dose administered. METHODS AND MATERIALS: In 35 patients treated with conservative surgery and axillary dissection, three clips were surgically positioned: one at the beginning of Level I, one between Level I and II, and another at the end of Level II. The breast was irradiated with two tangential fields. On simulation films, the volume between the clips was scored as "entirely included" or "not entirely included" in the treatment fields. Computed tomography (CT) scans were performed; CT data were imported into a treatment planning system, and three-dimensional plans were devised. Axillary Levels I and II were delineated on CT slices on the basis of anatomic landmarks. Fields and isodose curves previously obtained were superimposed to calculate the dose administered to the first two axillary node levels and to 90% of both volumes. RESULTS: On X-rays, the volume between clips corresponding to Level I was completely included in the medial field in 66.7% of cases and in the lateral field in 63.7% of cases, whereas the volume of Level II was entirely included in the medial field in 54.5% of cases and in the lateral field in 45.4% of cases. The median dose administered to Level I and II was 38.58 Gy +/- 11.01 (range 3.46-47.14) and 20.65 Gy +/- 14.07 (range 0.95-38.94), respectively. The median dose to 90% of both volumes of Level I and II was 6.75 Gy +/- 14.01 (range 1.9-39) and 1.75 Gy +/- 9.72 (range 0.8-29), respectively. CONCLUSION: The standard tangential fields do not entirely include Levels I and II axillary nodes.

Radiation-induced myelopathy in long-term surviving metastatic spinal cord compression patients after hypofractionated radiotherapy: a clinical and magnetic resonance imaging analysis.

BACKGROUND AND PURPOSE: Hypofractionated radiotherapy is often administered in metastatic spinal cord compression (MSCC), but no studies have been published on the incidence of radiation-induced myelopathy (RIM) in long-term surviving patients. Our report addresses this topic. PATIENTS AND METHODS: Of 465 consecutive MSCC patients submitted to radiotherapy between 1988 and 1997, 13 live patients (seven females, six males, median age 69 years, median follow-up 69 months) surviving for 2 years or more were retrospectively reviewed to evaluate RIM. All patients underwent radiotherapy. Eight patients underwent a short-course regimen of 8 Gy, with 7 days rest, and then another 8 Gy. Five patients underwent a split-course regimen of 5 Gy x 3, 4 days rest, and then 3 Gy x 5. Only one patient also underwent laminectomy. Full neurological examination and magnetic resonance imaging (MRI) were performed. RESULTS: Of 12 patients submitted to radiotherapy alone, 11 were ambulant (eight without support and three with support) with good bladder function. In nine of these 11 patients, MRI was negative; in one case MRI evidenced an in-field relapse 30 months after the end of radiotherapy, and in the other, two new MSCC foci outside the irradiated spine. In the remaining patient RIM was suspected at 18 months after radiotherapy when the patient became paraplegic and cystoplegic, and magnetic resonance images evidenced an ischemic injury in the irradiated area. The only patient treated with surgery plus postoperative radiotherapy worsened and remained paraparetic. Magnetic resonance images showed cord atrophy at the surgical level, explained as an ischemic necrosis due to surgery injury. CONCLUSIONS: On the grounds of our data regarding RIM in long-term surviving MSCC patients, we believe that a hypofractionated radiotherapy regimen can be used for the majority of patients. For a minority of patients, more protracted radiation regimens could be considered.

Total body irradiation-based regimen in the conditioning of patients submitted to haploidentical stem cell transplantation.

BACKGROUND AND PURPOSE: To evaluate the efficacy and toxicity of a highly immuno- and myelo-suppressive conditioning regimen followed by the infusion of large numbers of T-cell-depleted mismatched haematopoietic stem cells in 43 high-risk acute leukaemia patients. RESULTS: A high rate of engraftment (95%) and no graft-versus-host disease (GvHD) were observed. The 4-year probability of event-free survival was 0.25+/-0.09 for acute myeloid leukaemia and 0.17+/-0.07 for acute lymphoid leukaemia patients. CONCLUSIONS: This study shows that the main obstacles limiting the use of mismatched transplants, i.e. GvHD and rejection, were overcome.

The role of total body irradiation in the conditioning of patients receiving haploidentical stem cell transplantation.

BACKGROUND: Nearly 40% of patients requiring a hematopoietic stem cell transplant lack a suitable donor. However, virtually all these patients have a potential family donor with whom they share one HLA haplotype. METHODS: We report the rationale for making hematopoietic stem cell transplantation from haploidentical related donors feasible, as well as the method followed to achieve this. Two studies are reported, designed to overcome the problem of rejection and graft-versus-host disease after haploidentical stem cell transplantation. We describe how our total body irradiation-based, highly immuno- and myelosuppressive conditioning regimens were developed and how they have been modified over the years in an attempt to improve the clinical outcome of high-risk acute leukemia patients receiving large numbers of extensively T-cell-depleted hematopoietic stem cell transplantations from full-haplotype mismatched family donors. RESULTS: A high engraftment rate and an extremely low incidence of graft-versus-host disease were obtained. Modifications of the pretransplant schedules allowed the reduction of transplant-related toxicity. CONCLUSIONS: The main obstacles that limited the use of haploidentical stem cell transplantation have been overcome. The procedure is now a reality that should be recommended in high-risk acute leukemia patients who do not have a suitable matched donor.

Short-course palliative radiotherapy in non-small-cell lung cancer: results of a prospective study.

From February 1993 to October 1997, 91 consecutive patients with inoperable (stage IIIB-IV) histologically confirmed non-small-cell lung cancer underwent palliative hypofractionated radiotherapy. Recently, the Medical Research Council studies on hypofractionated short-course radiotherapy (8.5 Gy x 2) have reported high control of symptoms caused by thoracic disease without toxicity. Based on these experiences and our previous positive trial on short-course radiotherapy (8 Gy x 2) in metastatic spinal cord compression, a prospective study of short-course palliative radiotherapy in non-small-cell lung cancer was carried out. The regimen was 16 Gy given in two 8-Gy fractions, 1 week apart. Eighty-one patients were evaluable for response to treatment. Forty-eight (59%) patients were 65 years or older. Forty (49%) patients were naive to radiotherapy, whereas 41 (51%) had previous cisplatin-based chemotherapy. All but four stage IV patients (95%) had poor Eastern Cooperative Oncology Group performance status (i.e., 2-3). Clinical palliation was achieved in 62 (77%) patients. Performance status improved in 59 (73%) patients. The median palliation time ranged from 28% to 57% of patient survival. The median survival from the beginning of treatment was 148 days (range, 5-681 days). No difference in overall survival according to stage and previous chemotherapy was observed. Only performance status conditioned survival (performance status 1-2 vs. performance status 3; p = 0.0289). Short-course radiotherapy gave good results in terms of clinical palliation for thoracic symptoms, even in patients with poor performance status and pretreated with chemotherapy. The median palliation time was approximately 50% of patient survival time. Treatment was generally well tolerated-only 4 (5%) patients experienced World Health Organization grade III dysphagia. No late toxicity was recorded. The two-fraction regimen had social and economic advantages compared with the conventional ones.

Improved outcome with T-cell-depleted bone marrow transplantation for acute leukemia.

PURPOSE: To eliminate the risk of rejection and lower the risk of relapse after T-cell-depleted bone marrow transplants in acute leukemia patients, we enhanced pretransplant immunosuppression and myeloablation. PATIENTS AND METHODS: Antithymocyte globulin and thiotepa were added to standard total-body irradiation/cyclophosphamide conditioning. Donor bone marrows were depleted ex vivo of T lymphocytes by soybean agglutination and E-rosetting. This approach was tested in 54 consecutive patients with acute leukemia who received transplants from HLA-identical sibling donors or, in two cases, from family donors mismatched at D-DR. No posttransplant immunosuppressive treatment was given as graft-versus-host disease (GVHD) prophylaxis. RESULTS: Neither graft rejection nor GVHD occurred. Transplant-related deaths occurred in six (16.6%) of 36 patients in remission and in seven (38.8%) of 18 patients in relapse at the time of transplantation. The probability of relapse was .12 (95% confidence interval [CI], 0 to .19) for patients with acute myeloid leukemia and .28 (95% CI, .05 to .51) for patients with acute lymphoblastic leukemia who received transplants at the first or second remission. At a median follow-up of 6.9 years (minimum follow-up, 4.9 years), event-free survival for patients who received transplants while in remission was .74 (95% CI, .54 to .93) for acute myeloid leukemia patients and .59 (95% CI, .35 to .82) for acute lymphoblastic leukemia patients. All surviving patients have 100% performance status. CONCLUSION: Adding antithymocyte globulin and thiotepa to the conditioning regimen prevents rejection of extensively T-cell-depleted bone marrow. Even in the complete absence of GVHD, the leukemia relapse rate is not higher than in unmanipulated transplants.

Comparison of two different radiotherapy schedules for spinal cord compression in prostate cancer.

AIMS AND BACKGROUND: To assess the clinical outcome and toxicity of two different radiotherapy (RT) schedules for the management of metastatic spinal cord compression from prostate cancer, we performed a prospective analysis of 44 patients with the complication. METHODS: Two different RT schedules were adopted, a split-course regimen of 5 Gy x 3, 4 days rest, and then 3 Gy x 5, and a short-course regimen of 8 Gy, 7 days rest, and then 8 Gy. The split-course RT was adopted for all prostate cancer patients referred to our center between 1986 and 1992. Starting in 1993, the short-course RT was added for patients with a poor prognosis (i.e., paresis or paraplegia, low performance status, and/or short life expectation), whereas others still underwent the split-course regimen. So, 27 (61%) patients were treated with the split-course and the other 17 (39%) with the short-course regimen. Medium follow-up was 48 months (range, 6 to 123). RESULTS: Back pain total response rate was 82%. Effectiveness of RT on motor and bladder capacity was conditioned by pretreatment status of patients. All 20 (100%) walking cases maintained the function, whereas 11 of 24 (46%) with motor impairment regained the ability. The difference in response rate was statistically significant (P < 0.001). All 36 (100%) patients, able to void at presentation preserved the capacity, whereas 3 of 8 (38%) with sphincter dysfunction no longer needed an indwelling catheter. Posttreatment neurologic status was the only factor found to affect survival. Median survival, 9 months for the whole group, was 10 and 2 months for posttreatment walking and nonwalking patients, respectively (10 vs 2 months, P < 0.001). Neither presence of other metastases nor RT regimen used (split vs short-course) conditioned response rate, duration of response or survival. Acute or late, severe toxicity was never recorded. No patient complained of spinal cord morbidity. CONCLUSIONS: Both split-course and short-course RT schedules were effective and without complications. Early diagnosis was the most important prognostic factor, but there was also recovery of function in about half of the patients unable to walk, and about one-third of patients with bladder dysfunction before treatment. Since length of the course of therapy is a factor with an important impact on the patient's quality of life, the short-course RT regimen adopted in the trial merits further investigation.

Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype.

BACKGROUND: In this study we tried to achieve successful transplantation in patients with acute leukemia with the use of hematopoietic stem cells from donors who shared only one HLA haplotype with the recipient (a "full-haplotype mismatch"). To prevent graft failure, large doses of T-cell-depleted hematopoietic stem cells were transplanted after a conditioning regimen of enhanced myeloablation and immunosuppression was administered to the recipient. METHODS: Forty-three patients with high-risk acute leukemia who were scheduled for transplantation received total-body irradiation, thiotepa, fludarabine, and antithymocyte globulin. The graft consisted of peripheral-blood progenitor cells that had been mobilized in the donor with recombinant granulocyte colony-stimulating factor and also, in 28 cases, bone marrow. Bone marrow from the donor was depleted of T lymphocytes by processing with soybean agglutinin and E-rosetting. T-cell depletion of peripheral-blood mononuclear cells was achieved by E-rosetting followed by positive selection of CD34+ cells. No post-transplantation prophylaxis against graft-versus-host disease (GVHD) was administered. RESULTS: In all the patients, full donor-type engraftment was achieved. In none of the patients who could be evaluated did acute or chronic GVHD develop. Regimen-related toxicity was minimal. Eleven of the 23 patients with acute lymphoblastic leukemia had a relapse, as did 2 of the 20 patients with acute myeloid leukemia. Transplantation-related mortality was 40 percent. After a median follow-up of 18 months (range, 8 to 30), 12 of the 43 patients were alive and free of disease. All surviving patients had a good quality of life. CONCLUSIONS: The main limitations of transplantation of bone marrow from donors who are matched with the recipient for only one HLA haplotype GVHD and graft failure - can be overcome. Since most patients have a relative with one haplotype mismatch, advances in this method will increase the availability of hematopoietic-cell transplantation as curative therapy for acute leukemia.

Interstitial pneumonitis in acute leukemia patients submitted to T-depleted matched and mismatched bone marrow transplantation.

PURPOSE: To identify factors that could contribute to interstitial pneumonitis (IP), which remains one of the major causes of morbidity and mortality after both matched and mismatched bone marrow transplantation (BMT). METHODS AND PATIENTS: Ninety acute leukemia patients received an allogeneic T-depleted matched (n = 54) or mismatched (n = 36) BMT. They were preconditioned with total body irradiation (TBI), thiotepa, rabbit anti-thymocyte globulin, and cyclophosphamide. The TBI scheme was hyperfractionated in matched, and a single dose in mismatched patients. The dose to the lungs was reduced in both groups. RESULTS: Five of the 54 matched patients developed IP. All cases were fatal. There were 16 cases of IP, 13 fatal, in the mismatched group. The probability of developing IP was 11.3 +/- 4.9% and 48.6 +/- 9.0%, respectively. The between-group difference was statistically significant (p < 0.0001). The type of transplant and the TBI scheme were the most important parameters for IP development in univariate analysis, whereas acute graft-versus-host disease, disease stage and sex were nonsignificant. Median follow-up was 342 days (range 17-2900). CONCLUSIONS: The low incidence of IP in matched patients and the lack of idiopathic cases are evidence for the validity of the TBI schedule. In contrast, the incidence in mismatched patients remains too high; therefore, new strategies should be studied in an attempt to lower it.

[Adjuvant radio-chemotherapy in cancer of the rectum treated with radical surgery and with high risk of recurrence. Preliminary results of a prospective study]. / Radio-chemioterapia adiuvante nel cancro del retto radicalmente operato e con alto rischio di ricaduta. Risultati preliminari di uno studio prospettico.

UNLABELLED: INTRODUCTION MATERIAL AND METHODS: From January, 1990, to December, 1995, 138 consecutive patients with radically resected stage II and III rectal and rectosigmoid cancers were treated with adjuvant radiochemotherapy. Eighty-one patients with 24 months' follow-up were assessable. Low anterior resection (LAR) was performed in 64 (79%) patients and abdominoperineal resection (APR) in 17 (21%). Twentynine (36%) stage II and 52 (64%) stage III patients entered the study. Within 45-60 days from surgery all patients received 5-Fluorouracil chemotherapy at the dose of 500 mg/m2/iv/d 1-5, every 4 weeks, for six cycles. Chemotherapy cycles 3 and 4 were administered at the same daily dose on radiotherapy days 1-3 and 29-31. Radiotherapy total dose consisted of 45 Gy/1.8 Gy/day administered in 5 weeks with 18 MV photon beam to the pelvis with the four field "box" technique. Perineal scar was encompassed only after APR. A boost dose of 5.4 Gy to the tumor bed was given in 3 fractions of 1.8 Gy. Median follow-up was 37 months (range: 24-74 months). RESULTS AND DISCUSSION: Overall recurrent disease was reported in 28 of 81 patients (34%): local, systemic and both local and systemic relapses in 9 (11%), 14 (17%) and 5 (6%) cases, respectively. According to local extension, recurrence rates were 10% and 48% in stages II and III, respectively. Five-year overall and disease-free actuarial survivals were 64% and 61%, respectively. Median time to relapse was 15 months (range: 7-43 months). Significant prognostic factors for better tumor control were: stage (II vs III), disease site (proximal vs distal rectum), the surgical procedure (LAR vs APR), the number of involved nodes (< or = 4 vs > 4) and no extracapsular node invasion. The recommended dose of combined radiochemotherapy regimen used in this trial was generally well tolerated. The incidence of any grade > or = 3 acute toxicity (according to WHO grading) was 20% diarrhea, 6% tenesmus and 4% myelosuppression. Five (6%) patients had cronic diarrhea and other 3 (4%) radiotherapy-related severe late toxicity which required surgery. CONCLUSIONS: This study seems to provide similar survival and recurrence notes to other radio-chemotherapy regimens published in the literature. However, a more aggressive approach is warranted in stage III patients considering the low 5-year survival recorded.

Short-course radiotherapy (8 Gy x 2) in metastatic spinal cord compression: an effective and feasible treatment.

PURPOSE: To evaluate the clinical outcome and toxicity of a short-course regimen of radiotherapy (RT) in selected metastatic spinal cord compression (MSCC) patients. METHODS AND MATERIALS: Between 1993 and 1995, 53 consecutive patients with MSCC from low radio-responsive primary tumors (non small cell lung, kidney, head and neck and gastrointestinal carcinomas, melanoma and sarcomas), or more radio-responsive ones (breast and prostate carcinomas, myeloma and lymphomas) with paresis, plegia, low performance status (PS ECOG > or = 2), and/or short life expectation, underwent short-course RT; a single fraction of 8 Gy repeated after 1 week in responders or stable patients, for a total dose of 16 Gy. Of 49 (92%) evaluable cases, 4 (8%) underwent surgery plus RT and the other 45 RT alone. Medium doses of parenteral dexamethasone (8 mg x 2/d) were given in all cases and precautional anti-emetics to those treated with fields covering the upper abdomen (20 of 49 cases). Median follow up was 25 months (range, 6-34). Response was assessed according to back pain, and motor and bladder capacity before and after RT. RESULTS: Pain relief was achieved in 67% of patients and motor function response rate reached 63%. Early diagnosis and therapy were very important in predicting response to RT; all but two (91%) pretreatment walking patients and all but one (98%) with good bladder function preserved these capacities. On the contrary, when diagnosis was late, only 38% of nonambulatory patients and 44% of those with bladder retention improved. Median survival was 5 months, with a 30% probability of survival for 1 year. Length of survival was significantly longer for patients able to walk before and/or after RT. Good agreement between survival and duration of response was found with no evidence of relapse in the irradiated spine. Sickness appeared only in a few cases. Slight esophagitis was more frequent: dysphagia for solid foods in one-third of patients irradiated on the thoracic spine. Late toxicity was never recorded. CONCLUSION: The short-course RT adopted gave a clinical outcome comparable with that resulting from more protracted regimens with only slight side effects. The use of a few large treatment fractions could be explored considering the associated advantages for patients and radiotherapy centers often overloaded by long patient waiting lists.

Allogeneic matched T-cell-depleted bone marrow transplantation for acute leukemia patients.

PURPOSE: We evaluated the efficacy and toxicity of a conditioning regimen designed to overcome the increased risk of rejection and relapse associated with T-cell-depleted bone marrow transplants. PATIENTS AND METHODS: Fifty-four patients with acute leukemia received an allogeneic T-depleted bone marrow transplant from an HLA-matched (n=52) or one locus mismatched (n=2) sibling donor between June 1989 and November 1993. Nineteen acute myeloid leukemia patients and 17 acute lymphoid leukemia patients were in complete remission, and 11 acute myeloid leukemia patients and 7 acute lymphoid leukemia patients were in relapse. Patients were preconditioned with hyperfractionated total body irradiation of 1.2 Gy three times a day on days -9 to -6 (total 14.4 Gy), 10 mg/kg thiotepa on day -5, 4 mg/kg rabbit antithymocyte globulin on days -4 to -1, and 50 mg/kg cyclophosphamide on days -3 and -2. RESULTS: All patients were fully engrafted at a median of 15 days after transplant. No patient rejected the transplant or developed acute or chronic graft-versus-host disease. Of 19 patients with acute myeloid leukemia in complete remission, 14 survive. Four of the 11 patients with acute myeloid leukemia in relapse survive. Twelve acute myeloid leukemia patients died (three of relapse, eight of toxicity, one of other causes). Eleven of 24 patients with acute lymphoid leukemia (one treated in relapse) are alive in complete remission; the other 13 died (nine of relapse, four of toxicity). Interstitial pneumonia, the main cause of toxic death, occurred in 9.26% of total patients. The median follow-up time at this writing is 30 months. CONCLUSIONS: The absence of rejection and graft-versus-host disease and the relatively low relapse and toxicity rates are evidence for the efficacy of our conditioning regimen.

Radiotherapy without steroids in selected metastatic spinal cord compression patients. A phase II trial.

A phase II trial was planned to investigate the feasibility of radiotherapy (RT) without steroids in 20 consecutive patients with metastatic spinal cord compression (MSCC), no neurologic deficits, or only radiculopathy, and no massive invasion of the spine at magnetic resonance imaging (MRI) or computed tomography (CT). Aiming at an early diagnosis, MRI or CT was prescribed for all cancer patients with back pain and osteolysis, even when there were no signs of neurologic spinal compression. All patients were given 30 Gy in 10 fractions over 2 weeks with no steroids. Back pain and motor capacity were the parameters adopted to verify response to RT. Sixteen of 20 patients (80%) were able to walk without support, and 14 (70%) had no radiculopathy. Seventeen of 20 cases (85%) achieved relief from back pain. Regarding motor function, all patients (100%) responded to RT because the 16 patients able to walk without support at diagnosis did not deteriorate and the other 4, who needed support, became ambulatory without motor impairment. Median survival time was 14 months. Eight of 20 (40%) treated patients are still alive (14 to 36 months after end of RT), fully ambulatory, and free from relapse in the treated spine. Acute side effects were documented in only 2 patients (10%) and were managed without steroids. The results of this study suggest that RT without steroids is a feasible regimen for MSCC patients with good motor function. Elimination of steroids from the standard treatment for MSCC avoids cortisone side effects above all in those patients with diabetes, hypertension, peptic ulcer, and other steroid-sensitive medical problems.

Induction chemotherapy with cisplatin, doxorubicin, and cyclophosphamide (CAP) in a combined modality approach for locally advanced and inflammatory breast cancer. Long-term results.

Thirty-one patients with locally advanced and inflammatory breast carcinoma (stage IIIA and IIIB) were treated with a combined modality approach between 1985 and 1989. All patients received as induction chemotherapy a combination of cisplatin, doxorubicin, and cyclophosphamide (CAP). Responsive patients and patients with operable stable disease underwent modified radical mastectomy followed by concurrent radiotherapy and CMF (cyclophosphamide, methotrexate, 5-fluorouracil) adjuvant chemotherapy. Thirty patients were evaluable for response to CAP. The rate of objective response to induction chemotherapy was 76.7% with 2 patients (6.7%) obtaining a complete response and 21 patients (70%) a partial response. Twenty-five patients were rendered disease-free after induction chemotherapy and surgery. Only 2 of these had pathological complete response (8%). The median overall survival was 48.7 months, the median time to progression was 22.4 months and the median disease-free survival was 29.1 months. The patients with noninflammatory breast tumor had a significantly better overall survival, disease-free survival, and time to progression. The overall survival and the time to progression were statistically superior in patients with primary tumor size < or = 8 cm. At a median follow-up of 6 years, 29% (95% CI, 13.05 to 45.01) of patients were alive and 28% (95% CI, 10.4 to 45.6) were disease-free. This combined modality treatment seems feasible with quite acceptable toxicity; the CAP combination is an effective alternative to the other standard chemotherapeutic regimens. Our results, although encouraging, are still poor, and new drugs and strategies are required to improve the long-term outcome.

Effectiveness of radiation therapy without surgery in metastatic spinal cord compression: final results from a prospective trial.

PURPOSE: In assessing effectiveness of radiation therapy (RT) in metastatic spinal cord compression (MSCC), we performed a prospective trial in which patients with this complication were generally treated with RT plus steroids, and surgery was reserved for selected cases. METHODS AND MATERIALS: Two hundred seventy-five consecutive patients with MSCC entered this protocol. Twenty (7%) underwent surgery plus RT, another 255 received RT alone. Of all eligible patients, 25 (10%) early deaths and 21 (8%) entering a feasibility study of RT without steroids, were not evaluable. Of the 209 evaluable cases, 110 were females and 99 males, and median age was 62 years. Median follow-up was 49 months (range, 13 to 88) and treatment consisted of 30 Gy RT (using two different schedules) together with steroids (standard or high doses, depending on motor deficit severity). Response was assessed according to back pain and motor and bladder function before and after therapy. RESULTS: Back pain total response rate was 82% (complete or partial response or stable pain, 54, 17, or 11%, respectively). About three-fourths of the patients (76%) achieved full recovery or preservation of walking ability and 44% with sphincter dysfunction improved. Early diagnosis was the most important response predictor so that a large majority of patients able to walk and with good bladder function maintained these capacities. When diagnosis was late, tumors with favorable histologies (i.e., myeloma, breast, and prostate carcinomas) above all responded to RT. Duration of response was also influenced by histology. Favorable histologies are associated to higher median response (myeloma, breast, and prostate carcinomas, 16, 12, and 10 months, respectively). Median survival time was 6 months, with a 28% probability of survival for 1 year. Survival time was longer for patients able to walk before and/or after RT, those with favourable histologies, and females. There was agreement between patient survival and duration of response, systemic relapse of disease being generally the cause of death. CONCLUSION: Early diagnosis of MSCC was a powerful predictor of outcome. Primary tumor histology had weight only when patients were nonwalking, paraplegic, or had bladder dysfunction. The effectiveness of RT plus steroids in MSCC emerged in our trial. The most important factors positively conditioning our results were: the high rate of early diagnoses (52%) and the number of tumors with favorable histologies (124 out of 209, 63%) recruited, and the choice of best treatment based on appropriate patient selection for surgery and RT or RT alone.