Role of prognostic factors in the therapeutic strategy of primary gastric non Hodgkin's lymphomas.

PURPOSE: To evaluate retrospectively in 64 gastric non-Hodgkin lymphoma (G-NHL) patients the role of some prognostic factors in the therapeutic strategy of this disease. PATIENTS AND METHODS: Sixty-four primary G-NHL patients (39 males and 25 females; median age: 57 years) were retrospectively evaluated. Treatment consisted of surgery alone (S) in 7 patients, chemotherapy alone (CT) in 15, CT + radiotherapy (RT) in 2, S + RT in 2, S + CT in 19, S + CT + RT in 16. Three patients had no treatment. Forty-four patients received sub-total gastrectomy (21) or total gastrectomy (23), and 20 were not submitted to surgery. RESULTS: After a median follow-up of 106 months (range 48-201), the four-year disease free survival (DFS) was 56% and overall survival (OS) was 59%. In the univariate analysis, tumor invasion depth (p = 0.007), stage (IIE1 vs IIE2: p = 0.007; I-IIE1 vs IIE2-IV: p = 0.0000009) and treatment (in stage IE-IIE1: p = n.s.; in stage IIE2-IV: p = 0.002) were significantly different. In the multivariate Cox regression model, stage was the only significant variable negatively influencing survival. CONCLUSIONS: Our study confirms the prognostic value of both the depth of invasion and the disease stage. In patients with early disease stages and disease localized to the gastric wall, a conservative approach can be recommended. No difference was found between the sub-total and total gastrectomy but surgery retains its fundamental role for G-NHL, even in advanced disease. Prospective trials are needed to confirm these results.

Neoadjuvant chemotherapy with accelerated CNF plus G-CSF in patients with breast cancer tumors larger than three centimeters: a pilot study.

From February 1992 to November 1993, forty patients with operable breast cancer tumors larger than three centimeters were enrolled in this study of accelerated neo-adjuvant chemotherapy. Thirty-seven patients are evaluable: one patient was excluded from the protocol and two refused to continue treatment after the first cycle. Chemotherapy consisted of three presurgical cycles of CNF [cyclophosphamide at 600 mg/m2, mitoxantrone (Novantrone) at 10 mg/m2 and 5-fluorouracil at 600 mg/m2] administered every 2 weeks, plus G-CSF (5 microg/kg s.c./day on days 7-12). Twenty-six of 37 patients (70%) achieved objective tumor response and were submitted to quadrantectomy. Toxicity was easily manageable. After a median 55-month follow-up (range 48-70), no locoregional recurrences were observed. Distant metastases occurred in 12/37 (32%) patients. The five-year disease-free (DFS) and overall (OS) survival were 58% and 80%, respectively. Accelerated CNF plus G-CSF proved to be a safe and tolerable regimen yielding a good clinical response thereby increasing the possibility of breast conservation surgery for patients otherwise candidates for mastectomy.

Three cycles of ABDV plus extended field radiotherapy in patients with poor prognosis early-intermediate stage Hodgkin's disease.

The aim of the study was to verify the possibility of treating patients with poor prognosis early-intermediate Hodgkin's disease with a combined modality therapy consisting of three cycles of ABVD followed by extended field irradiation (EFRT). No patient had bulky mediastinum or had previously been administered chemo- or radiotherapy. At pathological restaging, 40/44 (91%) evaluable patients achieved complete responses (CR). After a ten-year followup, freedom from progression (FFP), relapse-free survival (RFS) and overall survival (OS) were 80%, 83% and 81%, respectively. Of the prognostic factors, univariate analysis showed that only stage III negatively influenced RFS, but not OS. Toxicity was mild except for subclinical mediastinal fibrosis in 32.5% of CR patients. No patient reported reduced fertility. Two cases of second neoplasms were recorded: one ameboid glioma and one thymoma, both occurring within five years after discontinuing chemo-radiotherapy. Our data suggest that three cycles of ABVD preceeding EFRT is an effective treatment for poor prognosis early-intermediate stage Hodgkin's disease; nevertheless, stage III patients and some stage II patients with unfavorable prognostic factors should be treated with a more aggressive approach.

CEOP-B alternated with VIMB in intermediate-grade and high-grade non-Hodgkin's lymphoma: a pilot study.

PURPOSE: To improve response and toxicity in treatment of non-Hodgkin's lymphomas (NHLs), a prospective single-arm trial was initiated using cyclophosphamide, epirubicin, vincristine, prednisone, and bleomycin (CEOP-B) alternated with etoposide (VP-16), ifosfamide, mitoxantrone, and bleomycin (VIMB). PATIENTS AND METHODS: From December 1988 to April 1992, 60 consecutive previously untreated patients with intermediate- or high-grade NHL were admitted to the study and were assessable. Patient characteristics were as follows: 32% greater than 60 years of age, 63% with stage III to IV disease, 42% with a performance status (PS) of 2 or 3, 23% with high lactate dehydrogenase (LDH) levels, and 22% with two or more extranodal disease sites. Stage I and II patients received three cycles of CEOP-B/VIMB plus radiotherapy (RT) to involved fields; stage III and IV patients received four cycles of chemotherapy alone. RESULTS: The complete remission (CR) rate was 77%; actuarial 48-month overall survival (OS) and time to treatment failure (TTF) rates were 70% and 59%, respectively. With univariate analysis, CR, OS, and TTF rates were significantly influenced by serum LDH levels (P = .0485, P = .0017, and P = .0064, respectively) and performance status (P = .0005, P < .00005, and P = .0001, respectively). The actuarial 48-month disease-free survival (DFS) rate was 83% and was negatively influenced only by high-grade histology (P < .004). Toxicity was mild. A lower epirubicin dose-intensity (DI) was found in patients older than 60 years of age, with a borderline P value. Patients were divided into four groups according to the International Prognostic Factor Project; low-risk and low-intermediate-risk groups had similar OS and TTF rates; when considered together, they showed superior, but not statistically significant, OS and TTF rates as compared with the high-intermediate-risk group, which in turn had significantly superior OS and TTF rates when compared with the high-risk group. CONCLUSION: CEOP-B/VIMB compares favorably with third-generation regimens and results in lower toxicity.

Solitary plasmacytoma of bone and extramedullary plasmacytoma: two different nosological entities?

BACKGROUND: The relationship between solitary plasmacytoma and multiple myeloma is still unclear, but they can be distinguished by their different clinical course. Indicators of disease activity and extension, and of a possible evolution to multiple myeloma, have not been identified as yet. METHODS: Two cases of solitary plasmacytoma are described: one of the mandible and one extramedullary plasmacytoma (EMP) of the rhinopharynx. Pathologic data included immunohistochemical staining for heavy and light Ig chains, and for the proliferating cell nuclear antigen (PCNA). Analysis of the peripheral immunological status and serum parameters (beta 2 microglobulin, thymidine kinase, IL-2, IL-6 and soluble IL-2 receptor) was performed and correlation was made with the clinical status. Flow cytometry analysis of nuclear DNA content and S-phase cell fraction were also studied in both neoplasms. RESULTS: Solitary plasmacytoma of bone (SPB) showed important basal immunologic alterations and a marked increase in all serum parameters considered with respect to EMP. Ploidy analysis demonstrated an almost complete aneuploidy cell population for the SPB patient (80%), whereas in the EMP patient only 2% of the cells were aneuploid. The S-phase cells were 16% and 4%, respectively. PCNA index was 60% in SPB and 10% in EMP. CONCLUSIONS: Solitary plasmacytoma of the bone appeared to be a more aggressive form of plasmacellular neoplasia, distinct from EMP and similar to multiple myeloma. The study of serum parameters, together with analysis of PCNA, ploidy and S-phase fraction, can aid in better understanding disease activity, and in the choice of more adequate treatment. Moreover, serial analysis of some serum factors might be useful markers for monitoring the disease.

Bulky mediastinal Hodgkin's disease: results of a combined modality approach (ABVD/MOPP alternating chemotherapy plus radiation therapy).

BACKGROUND: Bulky mediastinal involvement is a challenging presentation of Hodgkin's disease (HD). Radiotherapy alone has provided a good response rate but also a high percentage of recurrences, and therefore many studies have been initiated to evaluate combined modality treatment. METHOD: In a prospective study 23 stage IIA/IIIB HD patients treated with ABVD/MOPP alternating chemotherapy and radiotherapy were evaluated with regard to overall (OS) and disease-free survival (DFS), acute and long-term toxicity. RESULTS: A 95% CR rate was obtained. Ten-year actuarial OS and DFS were 83 and 91%, respectively. Two patients (8.8%) relapsed 8 and 9 months after achieving CR. One patient (4.4%) died following severe bone marrow failure 25 months after diagnosis. No clinically evident acute or chronic cardiac or pulmonary toxicity was evident, and no second malignancies were observed. At the end of therapy 7/14 evaluable women became amenorrheal and remained so at their last follow-up. Two male patients were considered azoospermic on the basis of laboratory evaluation at the end of therapy, and after 68 and 122 months, respectively; 4 of 5 male patients had sexual intercourse freely but did not fertilize their partners. CONCLUSIONS: In our opinion and in agreement with available literature, chemotherapy has a fundamental place alongside radiotherapy in the treatment of bulky mediastinal HD. Combined modality treatment improves the disease-free survival obtained with radiotherapy or chemotherapy alone. In our experience a high percentage of patients (83%) can be considered cured without the need for second-line therapy. However, long-term and especially gonadal toxicity greatly influence the quality of life of these patients. Therefore treatment must be personalized according to age, sex, cardiopulmonary status and desire to preserve reproductive function.