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Biomedical subjects

V Vitale

Publications and source records attributed to V Vitale.

At least 73 records · Page 4Linked to original sources

Hodgkin's disease in adults: association with social factors and age at tonsillectomy. A case-control study.

The relationship between socio-economic characteristics, previous tonsillectomy, family history of cancer and risk of Hodgkin's disease (HD) was investigated in a case-control study. One hundred and sixty patients, aged 15-78, with histologically confirmed HD, and 185 hospital controls were interviewed. A statistically significant decrease in risk of HD was observed among subjects with large sibship size (RR = 0.63, C.I. 0.46-0.86) and among those who underwent tonsillectomy prior to the age of 10 (RR = 0.46, C.I. 0.22-0.94). High educational level was associated with an increased risk of HD (RR = 6.68, C.I. I.94-23.08). Analysis by age-group (15-39 yrs and 40 yrs or more) confirmed the role of high educational level as a risk factor in both young and old subjects, while the protective effect of tonsillectomy at an early age seems to be confined to young subjects. Analysis by histological subtype showed a statistically significant decrease in risk of HD in large sibship size for both nodular sclerosis (NS) and mixed-cell subtypes; the role of education and tonsillectomy was observed only for NS. These data confirm the role of social factors in HD risk and suggest a protective effect of tonsillectomy performed early in life that needs to be confirmed in larger population-based studies.

Adolescent↗

Chemotherapy versus radiotherapy in the management of ovarian cancer patients with pathological complete response or minimal residual disease at second look.

The management of patients with epithelial ovarian cancer with no or minimal residual disease at second-look laparotomy after aggressive surgery and platinum-based chemotherapy has not been definitively established. We report the results of a randomized study comparing three more courses of the same chemotherapy inducing the response (21 patients) with whole-abdomen radiotherapy (20 patients). Thirty-eight patients responded to first-line chemotherapy and three had stabilization of disease. In eight patients tumor debulking was performed at second-look laparotomy. No severe toxic effects were noted in both arms. Bowel obstruction occurred in one patient treated with radiotherapy. At a median follow-up of 22 months, 11 of 20 patients in the radiotherapy arm and 6 of 21 in the chemotherapy arm progressed and 9 and 3 patients died, respectively. Although the number of randomized patients is small we stopped the trial because of the survival and progression-free survival advantage of chemotherapy-treated patients.

Antineoplastic Combined Chemotherapy Protocols↗

Chemo-radiotherapy and autologous bone marrow transplantation in poor prognosis neuroblastoma.

In Genoa, 39 patients affected by disseminated neuroblastoma, one to twelve years old, were treated with intensive chemotherapy (Vincristine 4 mg/sqm c.i. over 5 days, Melphalan 140 mg/sqm), total body irradiation (TBI) (3.3 Gy for 3 days), and unpurged autologous bone marrow transplantation (ABMT) since October 1984 until November 1987. Thirty-two patients were in complete response (first group) and 7 had residual disease (second group) after an intensive chemotherapeutic induction regimen. Actuarial overall survival at 38 months is 52% and disease free survival at 30 months is 28% for the first group. Actuarial overall survival at 25 months is instead 14% for the second group related treatment toxicity has not been too high (3 deaths).

Antineoplastic Combined Chemotherapy Protocols↗

Total body irradiation before allogeneic and autologous bone marrow transplantation: a ten year Genoa experience.

Since 1976 in Genoa, 291 TBI treatments were performed. Before allogeneic BMT, 1000 cGy/1 fx were prescribed in the first 22 patients, and then 990 cGy/3 fx/3 d in AML and CML, and the same or 1200 cGy/6 fx/3 d in ALL. Survival (S) and probability of remaining in remission (PRR) were 54% and 69% at 80 months in 80 AML; in 62 CML 45% and 60% at 60 months; in 69 ALL, 32% and 45% at 82 months. Differences in favour of higher doses and dose rates were observed and are presented. Before autologous BMT, 1000 cGy/1 fx were prescribed to AML and NHL, and 1200 cGy/3 fx/3 d to ALL patients. Disease free survival (DFS) was 71% and 13% at 82 months in 21 AML treated in first R and 9 ALL, respectively; 81% at 32 months in 11 NHL treated in R.

Clinical Protocols↗

Randomized comparison of two chemotherapy, radiotherapy schemes for stage III and IV unresectable squamous cell carcinoma of the head and neck.

Between August 1983 and December 1986, 116 previously untreated patients with squamous cell carcinoma of the head and neck were randomized to receive induction chemotherapy followed by radiotherapy given in conventional fractions (55 patients, arm A) or an alternating chemotherapy and radiotherapy (3 courses of 20 Gy, 10 daily fractions each; 61 patients, arm B). The same chemotherapy was used in both arms: 6 mg/m2 vinblastine sulfate, hour 0; 30 mg bleomycin, hour 6; 200 mg methotrexate, hours 24 to 26; 45 mg leucovorin, hour 48. Forty-five patients had stage III disease and 71 had stage IV disease. All patients were evaluated for survival, 112 for toxicity, and 105 for analyses of response and time from the start of treatment until progression of disease. At the end of the combined treatment, we observed an overall response rate of 52% in arm A and an overall response rate of 64.9% in arm B. The incidence of mucositis was more relevant in arm B compared to arm A (P less than .00004). The difference in complete response, progression-free survival, and survival was statistically significant, with an advantage for arm B (P less than .03, P less than .02, and P less than .03, respectively). The analysis at a median follow-up of 36 months (range = 19 to 59) demonstrates a higher effectiveness for the alternating program.

Adult↗

Mixed chimerism after allogeneic marrow transplantation for leukaemia: correlation with dose of total body irradiation and graft-versus-host disease.

Fifty-four patients allografted for leukaemia were evaluated at various intervals after bone marrow transplantation for the presence of host haemopoiesis using red blood cell and cytogenetic markers. Out of 40 patients in remission, 10 showed functional host and donor haemopoiesis (mixed chimerism), whereas in the other 30 (complete chimerism) host haemopoiesis was never detected. Seven of the 14 evaluable patients who relapsed showed the reappearance of host haemopoiesis at the time of relapse. Analysis of the dose of total body irradiation (TBI) indicated that patients who achieved mixed chimerism, whether or not they relapsed, had received significantly lower doses than those with complete chimerism. However, some patients with complete chimerism had received a TBI dose equivalent to the dose received by those with mixed chimerism, suggesting that the TBI dose is not the only factor determining the reappearance of host haemopoiesis. The data on chimerism and relapse suggest that there is heterogeneity in radiosensitivity between normal marrow cells and leukaemic cells, and also within the different types of leukaemia. The incidence/severity of acute and chronic graft-versus-host-disease (GVHD) was significantly higher in patients with complete chimerism than in mixed chimeras, suggesting that mixed chimerism may play a role in the development of tolerance. Alternatively the absence of GVHD (i.e. tolerance) may be responsible for the persistence of host haemopoietic cells.

Bone Marrow Transplantation↗

[The predictability of the radiotherapy response in epidermoid tumors of the head and neck. A review of the literature and mathematical models for choosing the fractionated doses].

Literature data show that the term "squamous-cell head and neck cancer" includes a wide range of epidermoid cell subgroups, each of them with its own intrinsic radiosensitivity (Do values ranging from 107 to 184 in primary tumors, and 146-263 in recurrences; n values ranging from 1 to 5; and, if we consider linear-quadratic model alpha values from 0.273 to 0.490 and beta values from 0.029-0.045). Different sublethal and potential lethal repair times are also observed (4-6 hours and 12-24 hours, respectively), and structural tissue heterogeneity (hypoxic fraction oscillating 5%-30% of the neoplasm). Most important, different kinetic parameters are demonstrated, with Labelling Index ranging from 4% to 30%, phase-S time from 6 to 19 hours, and potential doubling time from 2 to 20 days. On the basis of Fowler's and Barendsen's mathematical models and knowing the potential doubling time and Labelling Index values (derived from bioptic specimens), as well as alpha/beta ratio for both tumor and normal tissue, we tried to identify the optimal fractionation (standard, accelerated, hyperfractionated) for slow/fast-growth tumors, also evaluating the relative acute and late side effects. Our analysis shows that: 1) tumors with aggressive biological behavior (Labelling Index greater than 15%, aneuploidy, potential doubling time less than 5 days) seem to respond to accelerated fractionation/hyperfractionation without split better than to standard regimens: 2) tumors with slow growth (Labelling Index less than 15%, potential doubling time greater than 5 days, euploidy) seem to respond not only to standard regimens, but also--and mainly--to hyperfractionation.

Carcinoma, Squamous Cell↗

[A proposal for the treatment technique for the breast and regional lymph nodes in patients with conservatively operated neoplasms].

Adequate irradiation of regional lymph-nodes in selected patients seems to improve disease-free and over-all survival rates. Technically, regional lymph-nodes are generally treated separately (supra-infra clavicular, apex of axilla and internal mammary chain-IMC). About the treatment of the IMC nodes, there are two main problems: the identification of the individual target volume, and its correct irradiation. For the latter problem, the most employed solutions are: the inclusion of IMC in the tangential fields, the use of the direct or oblique electron beam for IMC alone. None of them is optimal regarding to the tolerance of adjacent critical organs and from a geometric and dosimetric point of view. In this paper we propose and discuss a modified method. The IMC nodes together with the breast are irradiated by a three field technique (two tangential photon beams and one oblique electron beam). Their arrangement allows to treat every part of the target by two fields, reducing the risk of hot and cold spots. This is obtained by extending the internal tangential photon beams to cover the electron beam. Wedges and different weights must be used to achieve an uniform dose distribution.

Breast Neoplasms↗

[The role of radiotherapy in the multimodal treatment of locally advanced breast carcinoma].

From September 1983 to March 1988, 57 patients with locally-advanced breast cancer were treated at the Istituto Nazionale per la Ricerca sul Cancro in Genoa, Italy. All patients received 3 cycles of induction chemotherapy with estrogenic recruitment before surgery (diethylstilbesterol-DES-FAC) and 6 additional cycles of chemotherapy (3 DES FAC alternating with 3 DES CMF) after surgery. Stage III A (15) patients reached 86% local relapse-free survival (LRFS), 68% disease-free survival (DFS), and 85% overall survival (OS). Stage III B (42) patients had 82% LRFS, 59% DFS, and 33% OS at 5 years. The first site of relapse was locoregional in 35% of the patients: 19% chest wall recurrence, 3.5% chest wall and lymph nodes, and 7% regional nodes; 5% of the cases presented synchronous local and systemic recurrence; distant metastases represented 21% of the initial relapse rate. This therapy appears to improve the prognosis of III A patients more than that of III B patients. Unsatisfactory results were obtained in inflammatory cancer, with 54% of local recurrences. The present study indicates that radiotherapy is necessary to improve local control and to increase DFS in inflammatory breast cancer. Moreover, the use of radiation therapy also improves the results in III A and III B patients.

Adult↗

Total body irradiation in acute myeloid leukemia and chronic myelogenous leukemia: influence of dose and dose-rate on leukemia relapse.

From June 1981 to March 1987, 106 patients--59 with acute myeloid leukemia (AML) and 47 with chronic myelogenous leukemia (CML)--were treated with Cyclophosphamide 60 mg/kg X 2 d and total body irradiation (TBI-990 cGy/3fr/3d described dose) before allogeneic bone marrow transplantation. Seventy-nine patients are evaluable for risk of relapse: 32 with chronic myelogenous leukemia (23 in first chronic phase, 9 in accelerated phase) and 47 with acute myeloid leukemia (38 in first complete remission, 9 in subsequent phases). Actual TBI doses delivered to these patients varied between 839 and 1250 cGy (mean 956 +/- 101)/3 fr/3d, with dose rates between 2.7 and 7.25 cGy/min (mean 4.2 +/- 1.8). Patients receiving high (greater than 990 cGy) and low (less than or equal to 990) dose and/or dose rate (greater than 4 cGy/min and less than or equal to 4, respectively) have been evaluated overall and stratified by type of leukemia and phase of disease. When the patients are considered altogether, high total dose is significantly correlated with decreased risk of relapse (p = 0.0005) as well as high dose rate (p = 0.03). When considering specific subgroups, the influence of total dose on relapse rate is evident both for "early" and "advanced" leukemias, while an impact of dose rate appears only for chronic myelogenous leukemia in 1st chronic phase. Pertinent radiobiological and clinical literature is reviewed, and a possible role of dose fractionation and dose rate in leukemic control rate is evidenced; in this TBI setting, total dose not less than 990 cGy/3fr/3d and dose rate not less than 4 cGy/min have to be guaranteed.

Adolescent↗

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.

Adolescent↗

[Fractionated and hyperfractionated total body irradiation in the conditioning of allogenic bone marrow transplant in acute lymphatic leukemia. Results].

Two different Total Body Irradiation (TBI) regimens were employed (1981 to July 1983) in Genoa in the conditioning program for the allogeneic Bone Marrow Transplantation (BMT) of 22 patients suffering from Acute Lymphoblastic Leukemia (ALL) in remission (7 patients in 1st remission, and 15 in 2nd remission). All patients were treated with Cyclophosphamide -60 mg/kg administered for two consecutive days (day -7 and -6)--and subsequently underwent fractionated TBI (days -3, -2, -1), that is, our conventional TBI regimen: 3.3 Gy/day per 3 days (total dose: 9.9 Gy). From August 1983 through 1988, 33 patients (14 in 1st remission and 19 in 2nd remission) were given 2 Gy twice a day, 6 hours apart, for 3 consecutive days (total dose: 12 Gy). Cyclosporine A was used for GvHD prophylaxis. At 58 months, out of the total figure of ALL patients in 2nd remission, 19% of those treated with 9.9 Gy/3 fr/3 days (fractionated TBI) is likely to be in remission, versus 65% of the cases treated with 12 Gy/6 fr/3 days (p less than 0.01) (hyperfractionated TBI); the actuarial overall survival is 23% after fractionated vs 60% after hyperfractionated TBI (p = 0.05). The incidence of idiopathic interstitial pneumonitis was very low (3.6%). Thus, we conclude that, in ALL patients in second remission, hyperfractionated TBI (12 Gy/6 fr/3 days) yields better results than fractionated TBI (9.9 Gy/3 fr/3 days), with lower relapse rate (33% vs 83%) and higher survival.

Adolescent↗

Moving-strip abdomino-pelvic radiotherapy after cis-platinum-based chemotherapy and second-look operation. A feasibility study in advanced ovarian cancer.

Sixteen FIGO stage IIB-IV ovarian carcinoma patients who completed six to 12 courses of a cisplatinum-based combination chemotherapy and with minimal (less than 2 cm), microscopic, or no residual disease at second-look laparatomy received moving-strip abdomino-pelvic radiotherapy. Radiation treatment was feasible with acceptable toxicity; two patients had to interrupt therapy--one pretreated with 12 PAC courses because of WHO grade III leukopenia and the other because of grade III diarrhea. A third patient required surgery because of intestinal obstruction 1 month after cessation of radiotherapy. In patients with minimal residual disease at second look, the therapeutic value of sequential radiotherapy was unsatisfactory (five of six progressed), while further investigations were warranted in patients with no or microscopic residuum after second-look operation.

Aged↗

[Sequential or alternate chemo-radiotherapy in the treatment of advanced head and neck tumors. Results of a randomized study].

Between 1983 and 1986, a multicenter randomized study was conducted to compare a sequential program of induction chemotherapy (CT) followed by radiotherapy (RT), Arm A, with an alternation of 4 cycles of CT with 3 courses of RT (20 Gy/10 fractions up to a total dose of 60 Gy), Arm B, in advanced head and neck cancer patients. The same CT (VBM: Vinblastine, Bleomycin, Methotrexate) was used on both arms; one hundred and sixteen patients (pts) entered the study, 55 in Arm A, 61 in Arm B. Fourty-five pts had stage III and 71 stage IV cancers. The two arms are fully comparable. Up to October 1987, 116 pts are evaluable for survival, while 112 are evaluable for toxicity and 105 for response. In 21 patients (10 in Arm A, 11 in B) the association CT-RT was followed by surgery. Response analysis shows 14 complete responses in Arm A and 30 in Arm B (p less than or equal to 0.03). The median disease-free survival and median overall survival are also statistically different, with an advantage for Arm B (33 vs 22 weeks, p less than or equal to 0.0007, and 59 vs 38 weeks, p less than 0.03 respectively). The actuarial overall survival of complete responders at 50 months is 43% (B) and 21% (A). Toxicity (mainly stage III-IV mucositis) is superior in Arm B (30% vs 4%). Our experience demonstrates the advantages of alternate over sequential CT-RT. A comparison of this cyclic association with RT alone is in progress.

Actuarial Analysis↗