Daniele Scarpati

Alternating chemo-radiotherapy in bladder cancer: A conservative approach

PURPOSE The aim of this Phase II study was to determine a bladder-sparing treatment in patients with invasive bladder cancer, allowing a better quality of life. Objectives were to test toxicity and disease-free and overall survival of patients given an alternated chemo-radiotherapy definitive treatment. METHODS AND MATERIALS Seventy-six patients with bladder cancer Stage T1G3 through T4 N0 M0 were entered in the same chemotherapy regimen (Cisplatin 20 mg/mq and 5-Fluorouracil 200 mg/mq daily for 5 days) alternated with different radiotherapy scheduling, the first 18 patients received two cycles of 20 Gy/10 fractions/12 days each; the second group of 58 patients received two cycles of 25 Gy/10 fractions/12 days each (the last 21 patients received Methotrexate 40 mg/mq instead of 5-Fluorouracil). RESULTS A clinical complete response was observed in 57 patients (81%), partial response in 7 patients (10%), and a nonresponse in 6 patients (9%). At a median follow-up of 45 months, 33 patients (47%) were alive and free of tumor. The 6-year overall survival and progression-free survival was 42% and 40%, respectively. Systemic side effects were mild, while a moderate or severe local toxicity was observed in 14 patients and 13 patients (about 20%), respectively. CONCLUSION Our conservative combination treatment allowed bladder-sparing in a high rate of patients and resulted in a survival comparable to that reported after radical cystectomy.

Perianal Paget's disease: case report of an elderly patient treated with polychemotherapy and radiotherapy.

The authors report a case of an 85-year-old patient suffering from perianal Pagets disease treated with polychemotherapy and radiotherapy, and followed for 30 months with no evidence of recurrence. Such treatment may be an effective alternative to surgical resection in elderly patients, although no definitive conclusion can be drawn due to the rarity of the disease.

Total body irradiation correlates with chronic graft versus host disease and affects prognosis of patients with acute lymphoblastic leukemia receiving an HLA identical allogeneic bone marrow transplant

PURPOSE To investigate whether different procedure variables involved in the delivery of fractionated total body irradiation (TBI) impact on prognosis of patients affected by acute lymphoblastic leukemia (ALL) receiving allogeneic bone marrow transplant (BMT). METHODS AND MATERIALS Ninety-three consecutive patients with ALL receiving a human leukocyte antigen (HLA) identical allogeneic BMT between 1 August 1983 and 30 September 1995 were conditioned with the same protocol consisting of cyclophosphamide and fractionated TBI. The planned total dose of TBI was 12 Gy (2 Gy, twice a day for 3 days). Along the 12-year period, variations in delivering TBI schedule occurred with regard to used radiation source, instantaneous dose rate, technical setting, and actual total dose received by the patient. We tested these different TBI variables as well as factors related to patient, state of disease, and transplant-induced disease to investigate their influence on transplant-related mortality, leukemia relapse, and survival. RESULTS At median follow-up of 7 years (range 3-15 years) the probabilities of leukemia-free survival (LFS) and overall survival (OS) for the 93 patients were 60% and 41%, respectively. At univariate analysis, chronic graft versus host disease (cGvHd) (p = 0.0005), age (p = 0.01), and state of disease (p = 0.03) were factors affecting LFS whereas chronic GvHd (p = 0.0005), acute GvHd (p = 0.03), age (p = 0.0001), and GvHd prophylaxis (p = 0.01) were factors affecting overall survival. The occurrence of chronic GvHd was correlated with actually delivered TBI dose (p = 0.04). Combined stratification of prognostic factors showed that patients who received the planned total dose of TBI (12 Gy) and were affected by chronic GvHd had higher probabilities of LFS (p = 0.01) and OS (p = n.s.) than patients receiving less than 12 Gy and/or without occurrence of chronic GvHd. Moreover, TBI dose had a significant impact on LFS in patients transplanted in first remission (p = 0.05). At multivariate analysis, TBI dose was an independent factor affecting overall survival (p = 0.05) as well as chronic GvHd (p = 0.001) and age (p = 0.04). CONCLUSIONS This retrospective analysis showed that different variables involved in TBI delivery may influence the occurrence of cGvHd and affect prognosis of patients with ALL receiving allogeneic BMT. The total dose of 12 Gy, administered in six fractions over 3 days, appears to be an effective and low toxic regimen for ALL patients transplanted in first remission.

The effect of total body irradiation dose and chronic graft-versus-host disease on leukaemic relapse after allogeneic bone marrow transplantation

One‐hundred and five patients undergoing allogeneic bone marrow transplantation (BMT) for acute myeloid leukaemia (AML) (n = 61) and chronic myeloid leukaemia (n= 44) were analysed for risk factors associated with relapse. All patients received marrow from an HLA identical sibling after preparation with cyclophosphamide 120 mg/kg and total body irradiation (TBI) 330 cGy on each of the three days prior to transplantation. There was a difference of ±18% between the nominal total dose of 990 cGy and the actual dose received as indicated by dosimetric recordings. While interstitial pneumonitis had minimal impact on survival (4%) there was a considerable difference in the incidence of relapses. The incidence of relapse was 55% versus 11% in patients receiving less or more than 990 cGy respectively and this had a major impact on survival (38% v. 74% at 7 years) since transplant‐related mortality was comparable in the two groups. A multivariate Cox analysis indicated that a lower TBI dose (less than 990 cGy) was the most significant factor associated with relapse and the second most important factor associated with recurrence of leukaemia was the absence of chronic graft‐versus‐host‐disease (cGvHD). Actuarial relapse incidence was 62%, 28% and 18% for patients with no, limited or extensive chronic GvHD respectively. However, chronic GvHD had no significant impact on survival. Combined stratification for TBI dose and cGvHD showed that the dose effect of TBI on relapse was evident both in patients with and without cGvHD. Chronic GvHD influenced the risk of relapse only in patients receiving less than 990 cGy. These results suggest that a higher dose of TBI, within this schedule, produced long‐term disease‐free survival in the majority of AMLs and CMLs. Minor radiobiological side effects were experienced, but a small reduction of the dose may significantly increase the risk of relapse.

Autologous bone marrow transplantation for advanced stage adult lymphoblastic lymphoma in first complete remission

Thirty-six successive adult patients with lymphoblastic lymphoma entered a study of sequential chemotherapy consisting of an intensive LSA2-L2-type protocol to induce first complete remission. Eighteen patients in first CR (median age 22 years, range 15–51), underwent autologous bone marrow transplantation after receiving a conditioning regimen consisting of cyclophosphamide and total body irradiation. Of these 18 patients, 2 were in stage III and 16 in stage IV; 15 showed mediastinal and 9 bone marrow involvement at diagnosis. The transplant procedure was well tolerated and no treatment-induced deaths occurred. At this time, 14 out of 18 patients are alive and well between 1 and 60 months post transplant (median follow-up time 46 months) with an actuarial disease-free survival of 74%. This phase II study suggests that high-dose chemo-radiotherapy followed by autologous bone marrow transplantation may improve long-term disease-free survival in advanced stage adult lymphoblastic lymphoma.

Non-functioning parathyroid carcinoma: a case report.

Non-functioning parathyroid carcinoma is a very rare disease. Only 12 cases have been reported in the literature. The clinical behavior is characterized by the appearance and growth of a neck mass or nodule, which often has been present for many years, and is not accompanied by clinical or laboratory evidence of hypercalcemia or elevated levels of parathyroid hormone (PTH) in peripheral blood. Pathologic findings are similar to those of functioning tumors, and the proof of malignancy is established on the basis of an increased mitotic index only. Data on survival from cases reported in the literature are not conclusive; however, the non-functioning type of parathyroid carcinoma seems to be a more aggressive disease. Radiotherapy seems to be effective in the local control of the disease, but most patients become metastatic. Even if no data are available on response to chemotherapy, the course of the disease is relatively indolent.

Bone Marrow Transplantation (BMT) for Acute Nonlymphoid Leukemia (ANLL) in First Remission

20 patients with acute nonlymphoid leukemia (ANLL) in first remission were given cyclophosphamide, 120 mg/kg, followed by total body irradiation (TBI) and an HLA-identical allogeneic marrow transplant (BMT). TBI was delivered in a single dose (10 Gy on day -1) in 2 patients, or in fractionated doses (3.3 rad/day on days -3, -2, -1) in 18 patients. The median age of patients was 22 years (range 2-44). Median time from remission to BMT was 5 months (range 1-12). 5 patients died of transplant-related toxicity (graft-versus-host disease with or without interstitial pneumonia) and 15 are alive 7-77 months post-BMT (median 20). The actuarial 72 months survival is 73%. There has been one relapse in a 2-year-old child, 4 months post-BMT, in the marrow and in the testis. The 72-month actuarial disease-free survival is 68%. The actuarial probability of relapse is 7%. This study indicates that a high proportion of ANLL patients treated in first remission with fractionated TBI and allogeneic marrow transplantation can become long-term disease-free survivors.

Measures of late effects in conservative treatment of breast cancer with standard or hypofractionated radiotherapy

Aims and Background To confirm the equivalence in terms of late effects between two fractionation schedules of radiotherapy in conservative treatment of breast cancer. Methods Fifty-eight patients treated at our institution from 1999 to 2002, with a median follow-up of 15 months (range, 7-46 months), were evaluated retrospectively. Twenty-nine patients (group A) were treated with standard fractionation: 5000 cGy/25fx/5 weeks, and 29 patients (group B) were treated with a hypofractionated schedule: 4500 cGy/15fx/5 weeks, three fractions per week. Late effects were evaluated using the LENT-SOMA scoring scale. The cosmetic results were assessed on a five-point scale. Skin elasticity was measured using a dedicated device (Cutometer SEM 575). Results There were no differences in breast volume, age at diagnosis and follow-up between groups. The LENT-SOMA toxicity observed in groups A and B, respectively, was as follows: grade 2-3 pain in five patients in each group; grade 2 breast edema in two and three patients; grade 2-3 and grade 2 fibrosis in six and eight patients; grade 2 and grade 2-3 telangiectasia in two and three patients; grade ≥2 and 2 arm edema in two and one patients; no ulceration or atrophy were observed. Two patients in group A and one patient in group B needed treatment for breast and arm edema and arm edema, respectively. Very good, good-acceptable, and poor cosmetic results were observed in seven and two, fifteen and nineteen, and six and eight patients, respectively. Median skin elasticity loss due to treatment was −4.19% in group A and −6.29% in group B. These results are not statistically different. Conclusions LENT-SOMA toxicities were minimal and no differences were observed between groups. Few patients in the hypofractionated group had very good cosmetic results, but it is debatable if radiotherapy was the only cause. Skin elasticity was not different between groups. Our results seem to suggest that it is possible to treat patients with both schedules, with similar late toxicity.

Neoadjuvant or definitive alternating chemotherapy and radiotherapy for infiltrating bladder cancer.

Thirty-two patients with infiltrating bladder cancer were treated with transurethral resection followed by one course of alternating chemoradiotherapy before radical cystectomy (group A, 20 patients) or two courses as definitive procedure (group B, 12 patients). One course consisted of: cisplatin 20 mg/m2 i.v. and 5-fluorouracil 200 mg/m2 i.v. for 5 consecutive days, the first and the fourth weeks; radiotherapy 20 Gy in 10 fractions in the second and third weeks. At the seventh week the same integrated therapy was restarted in group B. All 32 patients were evaluable for toxicity after the first course: no grade IV toxicity was observed. Significant increase in hematological toxicity was observed in 12 patients who received the second course of chemoradiotherapy: two patients had grade IV toxicity, and five patients had grade III. Fifteen patients of group A underwent radical cystectomy: 40% had a pathological (p) complete response (CR) and 13.3% a p-partial response. Five patients in group A did not receive either the second course of therapy or cystectomy because of age (three patients), vascular obliteration (one patient) and enteritis (one patient). Actuarial disease-free survival in group A is 78% at 21 months. All patients of group B obtained clinical (c) CR and all but one have no evidence of disease at a median follow-up of 10 months (range 6–13). The high pCR and cCR obtained in patients of group A and group B, respectively, appears promising. A longer follow-up and a larger number of patients is required to determine the role of this integrated treatment.

Autologous Unpurged Bone Marrow Transplantation for Acute Non Lymphoblastic Leukemia in First Remission

Forty consecutive adult patients under the age of 50 with acute non-lymphoblastic leukemia (ANLL) in first complete remission, underwent autologous bone marrow transplantation (ABMT) between March 1984 and April 1990. The conditioning regimen employed included cyclophosphamide and total body irradiation, followed by the administration of unpurged ABMT. The median time from diagnosis to transplant was 7 months (3-15 months), and the median time from complete remission to ABMT was 4 months (range 3-9 months). Twenty-two (51%) patients remain in complete remission 6-81 months (median 24 months) after ABMT. The causes of death were, recurrent leukemia (11 patients), parenchymal toxicities such as acute respiratory distress syndrome and veno-occlusive disease (3 patients), hemorrhage (2 patients) and infection (2 patients). Eleven patients relapsed after 3-12 months (median 5 months). This study has produced survival data comparable to those of other institutions employing TBI for either allo or autotransplants.