Carla Cavalli

HODGKIN'S DISEASE PROGNOSIS: A DIRECTLY PREDICTIVE EQUATION

586 patients with Hodgkins disease diagnosed between 1970 and 1979 were staged and treated in the same way. Multivariate analysis was used to delineate the prognostic roles of several clinical features at diagnosis. A multiple regression analysis was applied to an exponential model for survival-time distribution, which proved to fit the data accurately. Several clinical characteristics were studied and those that could singly discriminate survival significantly were chosen as predictive variables for the multiple regression. These were: sex, age, stage, histological subtype, presence of constitutional symptoms, mediastinal mass, and erythrocyte sedimentation rate (ESR), and haemoglobin and serum albumin concentrations. ESR, stage, histological subtype, and age proved to be the best prognostic factors, while sex and albumin had minor value. The presence of symptoms, mediastinal bulk, and haemoglobin were not so important. A linear equation for the six variables was derived to calculate the estimated median survival time for any given patient. This equation was validated on an external group of 179 similar patients.

Reevaluation of prognostic significance of symptoms in Hodgkin's disease

The prognostic value—at diagnosis—of fever, sweating and weight loss, which enter the Ann Arbor B category, and of pruritus, whose influence on survival is still debated, were systematically reevaluated in 635 patients with Hodgkins disease, observed between 1972 and 1982. By means of multivariate analysis an intrinsic, more negative prognostic value was demonstrated for each of the following symptoms: fever over 38°C, weight loss more than 10% of body weight in the 6 months before admission, and severe pruritus, which is defined as being generalized, causing multiple excoriations and resisting local and systemic antipruritics. Patients with the mild counterparts of these symptoms, as well as sweats, were found to have a survival rate quite comparable with that of fully asymptomatic patients. A rearrangement of the Ann Arbor B constitutional symptoms which would replace sweats with severe pruritus might be more correct and more suitable for better selecting the patients who require more aggressive therapy.

Serum albumin in Hodgkin's disease

Serum albumin levels were measured by electrophoresis in 552 evaluable patients with Hodgkins disease. Determinations were made on all patients at onset, on 224 after induction therapy and on 78 in relapse after remissions of variable length. At onset a discrete hypoalbuminemia was evident, inversely related to stage and more marked in symptomatic cases and elder patients. Little or no differences in albumin levels were found with relation to histologic subtypes, sex and presence of weight loss or hepatic damage. Posttherapeutic normalization of serum albumin occurred only after achievement of complete remission and failed after partial remission, while a new clear decrease became evident in relapse. On the basis of 799 albumin measurements during active disease and in remission, the albumin/α2‐globulin ratio demonstrated a clear and useful clinical advantage over either albumin or α2‐globulin fractions alone as indicator of active disease and relapse. If defective synthesis is the most accepted mechanism for hypoalbuminemia in Hodgkins disease, these results suggest a casual factor somehow related to the tumoral mass.

Ploidy and proliferative activity measurement by flow cytometry in non-hodgkin's lymphomas. Do speculative aspects prevail over clinical ones?

Paraffin-embedded lymph node biopsies from 107 patients with newly diagnosed non-Hodgkins lymphomas were examined for cell DNA content and proliferative activity (as percentage of S-phase cells) by means of flow cytometry. Patients were diagnosed between 1975 and 1985 and were homogeneously treated according to the grade of histologic malignancy. Cytofluorimetric data were studied with regard to their correlation with histology (classified and reviewed according to both Kiel and Working Formulation criteria), clinical stage, presence of constitutional symptoms, presence of bulky disease, sex, age, and the following laboratory data measured at diagnosis: erythrocyte sedimentation rate, hemoglobin, serum lactic dehydrogenase and serum albumin concentration. Aneuploidy was more frequent in the high grade malignant subtypes and in the miscellaneous group but showed no correlations with the other clinical parameters studied. Proliferative activity demonstrated a wide variation of data but a trend was evident toward higher proliferative values in the more severe histologic subtypes. The survival discrimination allowed by high- and low-grade malignant histology is exactly reproduced when highly and slowly proliferating lymphomas are considered (greater than or less than or equal to 12% of S-phase cells). These results, analyzed with those in the literature, suggest that measurements of ploidy and proliferative activity add little independent information to what is already provided by current histologic classifications, mainly as far as clinical evaluation and prognosis are concerned. Cytokinetic-aided therapeutic choices can be usefully proposed in a restricted number of cases. Improvement of the available lymphoma classifications through a better integration of ploidy and cytokinetic data with immunologic, genetic and histologic findings is still an object to be pursued in cytometric studies.

Increasing Interdependency of Prognosis- and Therapy-Related Factors in Hodgkin’s Disease

Two subsequent series of patients with Hodgkins disease (HD) treated according to different therapeutic plans were compared: the study made it possible to analyze the role played by therapy in influencing the individual importance of a group of well-known prognostic factors. Study 1 concerned 667 patients treated in the period 1971-1979 without special measures for mediastinal bulky disease and with four-drug chemotherapy regimens (MOPP, COPP, ABVD) for stage B or IV. Study 2 included 220 patients treated between 1980 and 1984 with combined sandwich chemoradiotherapy when mediastinal bulk was present, and with eight-drug alternating chemotherapy regimens for stages B or IV (MOPP/ABVD, CcVPP/ABVD). Distribution of epidemiologic and clinical characteristics as well as staging accuracy were comparable in the two series. Only sex, serum albumin at onset and success or failure in achieving complete remission showed the same ability to discriminate survival in both studies. Age, stage and histology retained a reduced role in Study 2, where it was found they could be handled as binary variables, i.e. more or less than 50 years of age, stage IV or other stages, lymphocyte depletion histotype or other types. The influence of B symptoms on survival was sharply decreased in patients treated with alternating chemotherapy regimens, whereas combined sandwich therapy showed a truly leveling effect on the role of mediastinal bulk, which has to be considered a very unfavorable factor with other treatments. In HD the evaluation of clinical findings with respect to their impact on prognosis is crucial for validating and graduating the staging process, and for matching the intensity of the therapy to the needs of the patient. The ongoing evolution in the roles of single prognostic factors due to therapy needs periodic reevaluation for proper adjustments of therapeutic strategies.

Prognostic Factors in Non-Hodgkin’s Lymphomas

Prognostic factors were investigated in 67 patients with non-Hodgkins lymphomas, homogeneously staged and treated (COP or CHOP according to low or high malignant histotype). A large number of parameters were scrutinized in order to recognize those exhibiting a prognostic value regarding length of survival. All the parameters that singly appeared to influence survival were entered into a multiple regression factor analysis. The erythrocyte sedimentation rate (ESR), higher or lower than 35 mm at the 1st h, better discriminated the groups of patients surviving or not at a given time. The histologic type, according to the Kiel classification of malignancy, was the second best prognosticator when a short-term prediction was requested (survival or death after no more than 2.5 years), but showed insufficient statistical weight for predicting longer survivals (greater than 4 years). Stage seemed to be the third best prognosticator for the first years of survival, but only the second best for longer survivals. Other parameters had very low prognostic importance when compared with those above. The results were substantially confirmed by 28 other patients, taken as controls. The importance that such a simple and easy test as ESR may be adequate with regard to prognosis is emphasized.

372PTARGETED CHEMOTHERAPY WITH ALBUMIN-BOUND PACLITAXEL (NAB-PACLITAXEL) FOR METASTATIC BREAST CANCER (MBC): WHICH BENEFIT FOR WHICH PATIENTS? A REAL WORLD MULTICENTER ITALIAN EXPERIENCE ON 150 WOMEN

ABSTRACT Aim: A growing evidence supports the efficacy and safety of different dosing schedules of nab-paclitaxel (nab-P) through several treatment lines in MBC, also in taxane-pretreated patients (pts). We report the final results of a multicenter experience with single-agent nab-P as 2nd and further chemotherapy (CT) in MBC, focusing on potential predictive and/or prognostic factors for treatment response and disease outcome. Methods: From February 2011, 150 consecutive MBC pts were treated at 8 Italian Institutions, 85 (cohort A) with the 260mg/m2 q3w schedule (46 in 2nd line, 21 in 3rd and 18 in ≥ 4th) and 65 (cohort B) with the 125 mg/m2 (20 in 2nd line, 10 in 3rd and 35 in ≥ 4th). Visceral involvement: 72%; ≥3 metastatic sites: 60%; median DFI ≤24 months: 35%; taxane-based CT in the adjuvant or metastatic setting: 68% and 65%, respectively. Results: The objective response rate (ORR) in the whole population was 48% (6 CR, 65 PR, 51 SD ≥ 16 weeks), for an overall clinical benefit rate of 83%. At a median follow-up of 18 months (range 6-30), median PFS was 7.8 months (range 3-23+), median OS has not yet been reached. Major toxicities were expected and manageable with both the schedules, without differences in the ≥65 years pts (38%). Statistical analysis showed no predictive or prognostic value of the evaluated patient- and disease-related variables (DFI, tumor subtype, site and number of metastatic sites, previous taxane-based CT, prior lines for metastatic disease, dosing schedules), while the line of CT significantly affected both the probability of response (61% ORR in 2nd line versus 38% in ≥3 lines; p Conclusions: Our data confirm that both the tested nab-P regimens produce encouraging ORR and PFS values in taxane-pretreated MBC, in advanced lines of treatment too. The suggested higher activity of the q3w schedule in pts with more aggressive disease further supports the possibility of tailoring the dosing schedules according to the different patient profiles and clinical situations. Disclosure: All authors have declared no conflicts of interest.