Loss of chromosome 1p may have a prognostic value in localised neuroblastoma: results of the French NBL 90 Study. Neuroblastoma Study Group of the Société Fran?aise d'Oncologie Pédiatrique (SFOP)

Between March 1990 and December 1994, 316 consecutive children with localised neuroblastoma were registered in the French NBL 90 study. In addition to the assessment of a new chemotherapy regimen in unresectable neuroblastoma, we evaluated the prognostic significance of MYCN amplification and loss of the short arm of chromosome 1 (LOH1p). MYCN was found in 22/225 children (10%) and associated with unfavourable clinical features such as age at diagnosis > 1 year and large and unresectable tumours. LOH1p was observed in 9/91 patients (10%), of whom some had favourable prognostic factors such as age at diagnosis < 1 year (n = 4), INSS stage 1 or 2 (n = 3) and no MYCN amplification (n = 4). Overall survival (OS) and event-free survival (EFS) were, respectively, 56% and 22% (median follow-up: 36 months) for children with LOH1p compared with 97% and 94% for those without (log-rank = 10(-8)). All except 1 of the 5 children with MYCN amplification and LOH1p relapsed and ultimately died of the disease. Among the 4 with LOH1p and no MYCN amplification, recurrence occurred in 3 (2 local, 1 metastatic), all alive in second remission after salvage therapy (12-19 months after the relapse). In multivariate analysis, LOH1p was the strongest prognostic indicator for subsequent relapse. LOH1p appears more discriminant than MYCN amplification for predicting the risk of recurrence in children with localised neuroblastoma. However, its analysis was possible in only 30% of our patients and its final impact on survival should be confirmed in larger, prospective studies in order to stratify subsequent treatment.     

Beta-interferon, retinoids and tamoxifen as maintenance therapy in metastatic breast cancer. A pilot study

BACKGROUND: Chemotherapy (CT), fundamental for the treatment of metastatic breast cancer (MBC), rarely cures, due to the presence of minimal residual disease (MRD). Based on the synergistic antiproliferative effect of interferon, retinoids and tamoxifen on breast cancer cell lines, we designed a pilot study to test if a combination of beta-interferon (beta-IFN), retinoids and tamoxifen could improve the progression free survival and overall survival in patients (PTS) treated with CT for MBC. METHODS: Thirty-six patients, with stage IV carcinoma of the breast, were treated with a combination of Cyclophosfamide, 5-fluorouracil, 4-epidoxorubicin, vincristine and prednisone every 3 weeks for six courses (FECPV), followed by two courses of methotrexate, mitomycin-c and mitoxantrone (MMM). Treatment was continued, in response, with low dose beta-interferon, retynil palmitate and tamoxifen until disease relapse. RESULTS: Among 36 evaluable PTS, 23 achieved a clinical response (64%) (95% c. i. 48 x 80%), 7 had disease stability (19%), and 6 (17%) progressed. Leukopenia occurred in 15 patients, thrombocytopenia in six, and anemia in 11. 16 patients had nausea/vomiting; stomatitis was observed in nine patients and diarrhea in three. Toxicity of maintenance therapy was mild and mainly hepatic. Median response duration was 31 months (range 5-75+). Median overall survival was 32 months (9-83+). CONCLUSIONS: Our study shows that this regimen is feasible and shows activity in MBC with an acceptable toxicity.     

Nodular lymphocyte predominance Hodgkin's disease: long-term observation reveals a continuous pattern of recurrence

We evaluated the presenting clinical characteristics and outcome of 68 patients with nodular lymphocyte predominance Hodgkin's disease (NLP-HD), in order to delineate the pattern of evolution of the disease. The male to female ratio was 46/22 and median age 35 yrs (range, 14-86). Eight patients had a history of benign hyperplasia on lymph node biopsies performed 6 to 36 months before the diagnosis of NLP-HD. Early stage disease accounted for 75% of cases. One patient had a coexistent non-Hodgkin's lymphoma (NHL). Treatment was as follows: radiotherapy in 26, chemotherapy in 23, combined modality in 19. CR rate was 93% (63/68). 18 patients relapsed as HD and 5 developed NHL. The cumulative risk of NHL was 9% at 10 yrs. During remission, 4 patients had 5 episodes of follicular hyperplasia histologically documented. Overall survival rate was 71% at 10 yrs and and 63% at 15 yrs. Freedom from progression (FFP) declined from 67% at 5 yrs to 45% at 10 yrs, because of late relapses. Localized disease predicted for a better FFP (p = 0.01), but was not associated with a reduced risk of recurrence over time. NLP-HD is characterized by an indolent course with a constant pattern of relapse over time, also in patients with early stage disease at diagnosis. In addition to relapse as NLP-HD, patients may evolve into a NHL or develop benign lymph nodal hyperplasia. Careful long-term follow up is needed for these patients.     

5-Fluorouracil, folinic acid, etoposide and cisplatin chemotherapy for locally advanced or metastatic carcinoma of the oesophagus

38 patients with advanced oesophageal carcinoma were treated with intravenous (i.v.) folinic acid (300 mg/m2), 5-fluorouracil (500 mg/m2), etoposide (100 mg/m2), and cisplatin (30 mg/m2) (FLEP), on days 1, 2 and 3, every 22-28 days. 26 patients had locally advanced disease (LAD) and 12 had metastatic disease (M1). Oesophagectomy was planned for patients with LAD in case of tumour regression after chemotherapy, while patients with M1 disease received chemotherapy only. The overall remission rate was 45% (17/38) including four clinical and two pathologically confirmed complete remissions. 16 patients underwent oesophagectomy, 12 after response to FLEP, and 4 after FLEP and subsequent irradiation +/- 5-fluorouracil/mitomycin. Toxicity was mainly haematological, with WHO grade 3 and 4 leukocytopenia in 50% and thrombocytopenia in 31% of the patients. Two treatment-related deaths were observed; one due to chemotherapy and one postoperatively. Median survival time of LAD patients was 13 months, and actuarial 2-year survival was 31%. Patients with complete tumour resection after FLEP had a median survival time of 18 months and a 2-year survival rate of 42%. Median survival of M1 patients was 6 months. FLEP is an active combination for oesophageal cancer, especially when used preoperatively in LAD.     

Adjuvant radio-chemotherapy in cancer of the rectum treated with radical surgery and with high risk of recurrence. Preliminary results of a prospective study

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.     

Laminin-6 and laminin-5 are recognized by autoantibodies in a subset of cicatricial pemphigoid

To aid treatment choice in early stage of Hodgkin's disease, we analysed patients registered in the IDHD Database with clinical stages I or II Hodgkin's disease who were not staged with laparotomy and whose initial treatment was with radiotherapy alone. The factors analysed for outcome after first relapse included initial stage, age, sex, histology, number of involved areas, mediastinal involvement, E-lesions, B-symptoms, erythrocyte sedimentation rate, alkaline phosphatase, serum albumin and haemoglobin. As well as presentation variables, we analysed the disease-free interval after initial radiotherapy and the extent of disease at relapse. A total of 1364 patients with clinical stage I or II Hodgkin's disease were treated with initial radiotherapy, of whom 473 relapsed. The probability of survival 10 years after relapse was 63%. For cause-specific survival (CSS), both multivariate and univariate analysis identified the importance of age at presentation and histological subtypes. When all causes of death were considered, the multivariate analysis identified age as the only significant factor. The length of initial disease-free interval had no influence on prognosis after relapse, but the 169 patients with nodal relapse had a higher cause-specific survival than those with an extranodal component of relapse (74% versus 51% at 10 years, P < 0.005). Thus, the important factors for outcome after initial treatment with radiotherapy are those factors predicting the risk of relapse after initial treatment together with those predicting outcome after relapse, namely age, histologic subtype and extent of disease at relapse.     

A fearsome enemy (1); A history of sanitation in the British Army 1899-1914

This study presents the results of a prospective study of methyl-gag, ifosfamide, methotrexate and etoposide (MIME) as salvage regimen for Hodgkin's disease (HD) in Sweden. Sixty-four patients with recurrent or refractory HD were treated with MIME between July 1988 and December 1993. All patients except one had, earlier, been treated with and failed consecutive or alternating MOPP and ABVD. Median age was 37 yr (range 14-73). Twenty patients (31%) achieved a complete remission (CR) and 17 (27%) a partial remission (PR), giving an overall response rate of 58%. The 5-yr survival for all patients was 43%. In a multivariate analysis, the most important factors predicting a poor survival were the presence of extranodal disease at relapse, male gender and high age. Twenty-nine patients were treated with high-dose chemotherapy with stem-cell rescue after MIME. Those patients had a similar survival compared to the patients responding to MIME but not treated with high-dose chemotherapy. We conclude that MIME induces remissions in a high proportion of patients with recurrent and refractory HD with acceptable toxicity. The remissions probably need consolidation, but the nature of this consolidation is still controversial.     

Stage T1-2 prostate cancer: a multivariate analysis of factors affecting biochemical and clinical failures after radical prostatectomy

PURPOSE: Prostate-specific antigen (PSA) is extensively used in case selection and outcome evaluation after treatment of clinically localized prostate cancer. Careful case selection can have a profound impact on pathologic findings and ultimate outcome. In addition, salvage treatment is frequently initiated at the time of biochemical relapse rather than clinical recurrence. Consequently, patterns of failure can be significantly altered compared to previous times when PSA was not available. To better understand the impact of PSA on pathologic findings, outcome, and salvage treatment, we reviewed our experience in the PSA era with clinical Stage T1-2 prostate cancer treated with radical prostatectomy. METHODS AND MATERIALS: Between 1987 and 1993, 423 cases could be identified with clinical Stage T1-2 prostate cancer treated with radical prostatectomy. The distribution of cases by pretreatment PSA levels was as follows: < or = 4 ng/ml (18%), 4-10 ng/ml (42%), 10-20 ng/ml (21%), > 20 ng/ml (14%), and unknown (5%). The median pretreatment PSA level for the entire group was 8.0 ng/ml. Sixteen patients received adjuvant or neoadjuvant androgen suppression and 13 received postoperative radiotherapy. Only 31 patients (7%) had pathologically positive pelvic lymph nodes. The overall margin involvement rate was 46%. Fifty-three percent of patients had surgical Gleason scores > or = 7, and 65% had extracapsular extension. The median follow-up time was 41 months. RESULTS: The projected overall survival at 7 years after surgery was 90%. The 5-year clinical relapse-free survival rate was 84%. At 5 years, the local control and distant failure rates were 92% and 91%, respectively. Biochemical relapse was defined as a detectable or rising PSA level after prostatectomy. The 5-year biochemical relapse-free survival (bRFS) rate was 59%. The 5-year RFS was 88% in patients with preoperative PSA levels < or = 4, 62% for 4-10, 48% for 10-20, and 31% for > 20. Combining the two independent preoperative variables, iPSA and biopsy GS (bGS), two risks groups were defined: low risk [initial PSA (iPSA) levels < or = 10.0 and bGS < or = 6] and high risk (iPSA levels > 10.0 ng/ml or bGS > or = 7). The 5-year bRFS rate for the low-risk cases was 81% vs. 40% for high-risk cases (p < 0.001). On multivariate analysis, three factors independently predicted biochemical relapse: iPSA levels (p = 0.005), Gleason score from the surgical specimen (sGS) (p = 0.002), and positive surgical margins (p < or = 0.001). The 5-year bRFS rates for margin positive vs. margin negative patients were 37% vs. 78%, respectively. The 5-year bRFS rates for GS > or = 7 vs. GS > or = 6 were 42% vs. 80%, respectively. All clinical relapses were accompanied by a rise in PSA. In patients who manifested biochemical failure followed by a clinical failure, the median interval between the PSA rise and clinical failure was 19 months (range 7-71). Margin involvement was the only independent predictor of local failure (p = 0.019). The 5-year local failure-free survival for negative margin cases was 96% vs. 87% for positive margin cases (p = 0.012). Lymph node (LN) involvement and high-risk group were the two independent predictors of distant failure. The 5-year distant failure-free survival for negative LN cases was 94% vs. 67% for positive LN cases (p < 0.001). The 5-year distant failure-free survival for low-risk cases was 97% vs. 85% for high-risk cases (p = 0.005). For the 124 patients failing biochemically, 85 were observed and 39 were treated either with radiation or androgen deprivation. With a median follow-up of 32 months, the clinical disease relapse-free survival was 79% for the treated patients vs. only 32% for the patients observed (p < 0.001). CONCLUSION: Pretreatment PSA is the most potent clinical factor independently predicting biochemical relapse, thereby allowing markedly better case selection. Achieving negative margins, even in relatively advanced disease, provides excellent lon     

Ewing's sarcoma of the ribs. A report from the cooperative Ewing's sarcoma study

31 patients with primary Ewing's sarcoma of the ribs were treated according to the protocols of CESS 81, CESS 86P and CESS 86. The results of treatment were reviewed and analysed. 24 patients presented with localised disease and 7 with regional disease. 20 of 24 localised cases and 6 of 7 regional cases underwent tumour resection. All but 2 localised cases received irradiation. The cumulative relapse-free survival (RFS) rate of 31 patients was 61% at 12.8 years. Patients with poor prognosis had tumour of the upper ribs (P = 0.0338), the posterior component of the ribs (P = 0.0597), or regional disease (P = 0.0001). Tumour size, existence of pleural effusion, type of the surgical margin and response to chemotherapy were not significant prognostic factors. Most of the localised cases could be controlled by combined treatment, but in regional cases prognosis remained poor.     

Paratesticular rhabdomyosarcoma in adult patients: 16-year experience at Institut Gustave-Roussy

BACKGROUND: Children with paratesticular rhabdomyosarcoma (RMS) have both a good prognosis and a high survival rate. The clinical behaviour and outcome of the disease in adults is not well described. PATIENTS AND METHODS: We reviewed retrospectively our experience with paratesticular RMS in patients older than 16 years during a 16-year period (1975-1991). RESULTS: Thirteen adult patients with paratesticular RMS are reported. Median age was 21 years (range 16 to 31). Presentation characteristics were scrotal mass in 11 cases, lumbar pain and weight loss in 5 cases, hypercalcemia in 3 cases and thrombocytopenia in 3 cases. There were 5 patients with stage IV, 2 with stage IIB and 6 with stage IA (IRS classification). The 5 stage IV patients are reported in detail, with initial bone marrow infiltration encountered in 4 of them. Objective response to chemotherapy was achieved in all 6 patients with measurable disease (2 CR + 4 PR). Two of 7 patients who received adjuvant chemotherapy relapsed at 7 and 11 months. After a median follow-up of 90 months, 8 patients (5 stage IV, 3 stage IA) died from disease progression. CONCLUSION: Metastatic disease with bone marrow involvement at presentation and aggressive behaviour seem to be more relevant in adult paratesticular RMS patients compared with children.     

Progressive disease after ABMT for Hodgkin's disease

A major limitation of ABMT for relapsed/refractory Hodgkin's disease is disease recurrence post-transplantation. We retrospectively reviewed 68 patients undergoing ABMT from January 1987 to June 1993. All received a uniform preparatory regimen (CBV). The median patient age was 30; 75% received prior radiation therapy and all patients received prior chemotherapy. Thirty-one percent presented at the time of transplantation with tumor masses larger than 10 cm. Sixty-two percent received autologous marrow alone and 38% PBPC with or without autologous bone marrow. Overall and progression-free survival are 43 and 36% at 5 years. Median follow-up for survivors is 59 months. Multivariate analysis revealed that tumor bulk was the most powerful poor prognostic factor for both survival and progression-free survival. Those transplanted with non-bulky tumors had an overall survival and progression-free survival of 52 and 44%, respectively, compared to those transplanted with bulky tumors who had an overall survival and progression-free survival of 22 and 16% (P = 0.03 and P = 0.04, respectively). Twenty-seven patients have relapsed. Four relapsed more than 2 years after ABMT. Four of the 27 patients who have relapsed remain alive, two without evidence of disease. The time after transplant to relapse was prognostically important, with no patients who relapsed within 6 months of ABMT still being alive, compared with 25% of patients who relapsed 7 or more months after ABMT who are still alive. We conclude that salvage therapy for relapse after ABMT is appropriate, as some patients may achieve prolonged survival. The time from transplant to relapse is an important survival predictor.     

Cortisol induces apoptosis in activated B cells, not in other lymphoid cells of the common carp, Cyprinus carpio L.

Two-hundred and 31 patients with a newly diagnosed multiple myeloma first seen and admitted to 17 hospitals located in the North-East of Italy between 1987 and 1992, were registered for a prospective study on the course of the disease. Median age was 68 years (range 41-90). Fifty-one per cent were in stage I, 9% in stage II and 40% in stage III. The presenting features and the survival of the 61 (26%) patients who were first admitted to a division of Hematology of a University Hospital (group HEM) were compared with those of the 170 (74%) patients who were referred to 16 divisions of Internal Medicine at General and County Hospitals (group INT). In the latter group, the patients were older (p = 0.002), had a poorer performance status ( p = 0.0001 ), a higher frequency of renal failure (p = 0.006) and anemia (p = 0.02) and higher beta2 microglobulin levels (p = 0.01). Median survival of group HEM patients did not differ significantly from group INT patients, if all stages were considered, but stage II and III patients of group INT had a significantly shorter median survival than advanced stage patients of group HEM (12 vs. 35 months, p = 0.01). If those older than 65 years or with unfavourable prognostic factors at presentation were excluded, prolonged survival of group INT patients was observed and the curves of the two groups did not differ significantly anymore. These results show that the patients recruited by a specialized centre may represent a selected population with better prognostic factors and younger age and this may affect analysis of clinical trials. Participation of minor centres in clinical trials may considerably contribute in improving interpretation of results of therapy in myeloma and be more representative of the entire population.     

Malignant lymphomas of sinonasal region, including cases of polymorphic reticulosis: a retrospective clinicopathologic analysis of 34 cases

BACKGROUND: Lymphomas occurring in nasal cavities and paranasal sinuses are uncommon neoplasms in Western, but are reported to be higher in Oriental, countries. A retrospective study was performed to analyze the clinical and pathological characteristics of sinonasal lymphomas/polymorphic reticulosis at Taichung Veterans General Hospital during a 14-year period. METHODS: At Taichung Veterans General Hospital, 37 patients with sinonasal lymphomas (including three patients with polymorphic reticulosis) were seen from November 1982 through September 1996. Excluding three patients without sufficient data, a total of 34 patients with their clinical records were reviewed. Clinical information regarding characteristics of the tumors, histological studies, treatment modalities and follow-up was collected for analysis. RESULTS: The 34 patients who underwent review showed a male-to-female ratio of 2.1:1. Median age was 60 years (range 13-83 years). The most common symptoms were nasal obstruction, nasal discharge/rhinorrhea and epistaxis. Median duration of symptoms at the time of diagnosis was two months. The most frequently involved sites were nasal cavities (right more than left side). There were 31 non-Hodgkin's lymphomas and three polymorphic reticuloses. The pathological classifications revealed 13 diffuse large cell lymphomas, 14 diffuse mixed small and large cell lymphomas and four pleomorphic T-cell lymphomas. Of the 21 adequately staged patients, 13 patients were in stage I; four, stage II; two, stage III and two, stage IV. The immunophenotypic study was performed in 20 patients. Eighteen (90%) of them were T-cell lymphomas and only two cases (10%) derived from B-cell. Though approach to therapy and follow-up periods varied during the time period covered by this study, the differences in survival according to treatment modalities were not statistically significant. The follow-up period ranged from 9 days to 130 months. The mean survival was 84.2 months. The overall five-year survival rate was 63%. CONCLUSIONS: The majority of the cases here were T-cell lymphomas. Most histologic grading by Working formulation belonged to the intermediate grade. Optimal treatment for such a group of patients still has no consensus, but adequate local control is important. If diagnosed and treated early, primary sinonasal lymphomas can be associated with a favorable outcome even with local treatment alone.     

Non-Hodgkin's lymphoma of the thyroid: a retrospective review of all patients diagnosed in Nottinghamshire from 1973 to 1992

The pathological and clinical features were reviewed of all primary non-Hodgkin's lymphomas (NHL) of the thyroid gland diagnosed between 1973 and 1992 in the population (1.1 million) served by the Nottingham and North Nottinghamshire Health Authorities. Of the 43 patients with histologically proven NHL, three had low grade mucosa associated lymphoid tissue (MALT) lymphomas (Stage IEA, 2; Stage IIEA, 1), 35 had intermediate or high grade lymphomas, Stage IEA or IIEA (intermediate MALT, 2; high grade MALT, 14; B-cell diffuse centroblastic, 17; anaplastic large cell (Ki-1) of null cell type, 1; high grade unclassifiable, 1), and one had unclassifiable NHL Stage IIEA. One patient had Stage IIIEA disease (high grade MALT) and three had stage IVA disease (high grade MALT, 2; B-cell diffuse centroblastic, 1). The median age was 68 years (range 45-86) with a female: male ratio of 6:1. For the 35 patients with intermediate or high grade thyroid NHL (Stages IEA and IIEA) the 5- and 10-year cause specific survival was 60%. The 21 patients treated between 1985 and 1992 initially with chemotherapy (except stage IEA (< 5 cm diameter) had a 5-year cause specific survival of 69% (95% CI 48-90) compared with 46% (95% CI 19-73) for the 14 patients treated between 1973 and 1984 with initial radiotherapy (Chi 2 = 1.62). The survival of those patients with intermediate or high grade MALT lymphomas was not significantly greater than of those patients with B-cell diffuse centroblastic NHL.     

Primary small-intestinal lymphomas in Taiwan: immunoproliferative small-intestinal disease and nonimmunoproliferative small-intestinal disease

PURPOSE: The clinicopathologic findings in 45 adult Chinese patients with primary small-intestinal lymphoma (PSIL) are described and compared with those in Western countries and in underdeveloped nations. The efficacy of combination chemotherapy is also assessed. PATIENTS AND METHOD: Six patients had immunoproliferative small-intestinal disease (IPSID) indicated by the presence of alpha-heavy chain protein (alpha-CP) in body fluids or tumor tissues. Thirty-nine patients had non-IPSID, including one with postrenal transplant lymphoma. Thirty-three non-IPSID patients received a minimum of four cycles of combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP). RESULTS: All IPSID patients presented with the clinical and laboratory features of severe intestinal malabsorption, and all had diffuse lymphoplasmacytic infiltration in the mucosa of the small bowel. Lymphomas were localized mainly in the jejunum and mesenteric nodes. The histologic subtypes were diffuse large cell in two, immunoblastic in three, and diffuse mixed in one. All patients responded poorly to chemotherapy, with a median survival duration of 10.5 months. The common presenting symptoms of the 39 non-IPSID patients included abdominal pain (90%), weight loss (31%), abdominal mass (26%), obstruction (26%), and perforation (23%). Diffuse large-cell and immunoblastic lymphomas constituted 82% of cases. Four patients had stage IE, 19 stage II 1E, and 16 stage 112E disease according to the Musshoff's criteria; 22 had bulky tumors and 19 had multiple tumors. The tumors were completely resected in 14 patients. Of 33 patients treated with combination chemotherapy, 73% achieved a complete remission. With a median follow-up duration of 90 months, there have been four relapses, with only one at the primary tumor site. The overall 5-year survival and disease-free survival rates for non-IPSID patients who were treated with chemotherapy were 59% and 54%, respectively. CONCLUSION: Intensive chemotherapy produces long-term disease-free survival in locally advanced non-IPSID PSIL.     

Pharmacokinetics of CDDP by the route of administration in patients with ovarian cancer

Seventy patients with local squamous cell carcinoma of the esophagus were treated between 1981 and 1990 with preoperative chemotherapy, surgical resection, and possible postoperative radiation therapy and/or chemotherapy. Chemotherapy included two cycles of 5-fluorouracil (1000 mg/m2) by continuous intravenous infusion on days 1-4 and cisplatin (100 mg/m2) on day 4. Complete clinical response (CCR) was achieved in 28 (41%) patients, partial clinical response (PCR) in 17 (25%), and no response in 23 (34%). Fifty-five (81%) patients were resected, 6 (9%) were explored, and 7 (10%) were unable to have surgery. Microscopic analysis of 55 resected patients showed 50 (91%) with active tumor, 1 (2%) with necrotic tumor, and 4 (7%) with a pathological complete response to chemotherapy. Twenty-six of the 55 resected patients (47%) had no gross evidence of disease at the time of surgical inspection. Median overall survival was 21.86 months (range 2-107 months) for all patients and 26.71 months (range 2-107 months) for resected patients. Actuarial 5-year survival rate was 31% for all patients and 39% for resected patients. Prolonged survival correlates with complete clinical response to chemotherapy, low pathological stage of disease, and successful resection of the lesion.     

Effect of prostaglandin A1 on proliferation and telomerase activity of human melanoma cells in vitro

BACKGROUND AND OBJECTIVE: Idarubicin, an anthracycline analogue, is active in non-Hodgkin's lymphoma. This study evaluates the efficacy and toxicity of a combination of idarubicin, etoposide and intermediate-dose cytarabine (IVA) in unfavorable lymphoma in relapse or resistant to prior doxorubicin- or novantrone-based regimens. DESIGN AND METHODS: Thirty patients with relapsing or resistant unfavorable lymphoma received a combination of idarubicin 12 mg/m2 i.v. on day 1, etoposide 60 mg/m2 i.v. every 12 hours for 3 days, and Ara-C 1 g/m2 i.v. every 12 hours for 3 days (3-hour infusion). Median age was 39 years (range: 22-60). All patients had been given prior doxorubicin or novantrone; 54% of them had received 2 or more chemotherapy regimens; 67% of total were in clinical relapse (30% in their second relapse), and 23% had resistant disease. RESULTS: The overall response rate to IVA was 60% (18 of 30 patients). Complete remission rate was 20% (6 of 30) in the whole group, 45% (5 of 11) among patients in their first relapse. Remission median duration was 9 months (range: 1-18), with a 3-year relapse-free and overall survival of 20% and 15%, respectively. Severe neutropenia occurred in 13 patients (43%) and severe thrombocytopenia in 11 patients (37%), with a median duration of 9 and 13 days, respectively. No cardiac toxicity developed; sepsis during neutropenia was documented in four instances and two patients (7%) died of therapy-related events (septic shock). INTERPRETATION AND CONCLUSIONS: Idarubicin combined with etoposide and intermediate-dose cytarabine proved to be an active salvage therapy in unfavorable lymphoma given prior doxorubicin or novantrone; the best results were obtained among patients in their first relapse, with low tumor burden.     

The position of internal medicine in Europe. Report from a meeting of the presidents of European internal medicine societies

A series of 48 cases of malignant mucosal melanomas treated at the Milan Cancer Institute from 1975 to 1990 is retrospectively reviewed. There were 34 males and 14 females, and their ages ranged from 21 to 79 years (mean, 58). The site of origin of the tumor was the nasal cavity in 26 cases, the oral cavity in 15, larynx in two, lip mucosa in two, pharynx in two and upper esophagus in one. At presentation, the neoplasm was limited to the primary site in 60.4% of the patients. Most patients (34) were treated with surgery alone. Nine were treated with surgery combined with chemo- and/or radiotherapy and five with radiotherapy combined with chemotherapy and/or immunotherapy. Only when surgery was part of the treatment (42 of 48 cases) the patients were rendered disease free, but no further relapse of disease was documented in only five of these patients. The observed 2- and 5-year survival rate of the entire group was 45% and 21%, respectively. The 4-year disease-free survival rate was 7%. The median interval between therapy and the first relapse was 8.5 months (range, 1-66). In 44% of the patients the first recurrence of the tumor was at the primary site.     

Androgen suppression plus radiation versus radiation alone for patients with D1 (pN+) adenocarcinoma of the prostate (results based on a national prospective randomized trial, RTOG 85-31). Radiation Therapy Oncology Group

PURPOSE: To evaluate the effect of immediate androgen suppression in conjunction with standard external beam irradiation vs. radiation alone on a group of pathologically staged lymph node-positive patients with adenocarcinoma of the prostate. METHODS AND MATERIALS: A national prospective randomized trial (RTOG 85-31) of standard external beam irradiation plus immediate androgen suppression vs. external beam irradiation alone was initiated in 1985 for patients with locally advanced adenocarcinoma of the prostate. One hundred seventy-three of the patients in this trial had biopsy-proven pathologically involved lymph nodes. Ninety-eight of these patients received radiation plus the immediate androgen suppression (LHRH agonist), while 75 received radiation alone with hormonal manipulation instituted at the time of relapse. RESULTS: With a median followup of 4.9 years, estimated progression-free survival with PSA < 1.5 ng/ml at 5 years was 55% for the patients who received radiation plus immediate LHRH agonist vs. 11% of the patients who received radiation alone with hormonal manipulation at relapse (p = 0.0001). Because all of these patients had locally advanced disease (i.e., pathologically positive lymph nodes), stage does not explain this difference in outcome, and Gleason grade was not statistically different between the two groups. Estimated absolute survival at 5 years for the radiation and LHRH group was 73 vs. 65% for the radiation alone group who received androgen suppression at relapse. Estimated disease-specific survival at 5 years was 82% for the radiation and immediate LHRH agonist group and 77% for the radiation-alone group. CONCLUSION: Patients with adenocarcinoma of the prostate and pathologically involved pelvic lymph nodes (pN+ or clinical stage D1) should be seriously considered for external beam irradiation plus immediate hormonal manipulation over radiation alone with hormonal manipulation at the time of relapse.     

Surgical treatment of primary lung cancer in patients less than 40 years of age

PURPOSE AND METHODS: The major purpose of this study was to determine whether the survival rate in young lung cancer patients after surgical treatment differs from that in older patients. An analysis was performed for all patients with bronchogenic carcinoma who underwent surgery at Mie University Hospital from 1965 to 1990. RESULTS: Of 803 patients, 24 (2.99%) were 33 to 39 years old. At the time of surgery, the disease was diagnosed as stage I in seven patients (29%), stage II in four (17%), stage IIIa in seven (29%), stage IIIb in two (8%), and stage IV in four (17%), while 46.3% of the patients older than 40 years of age had either stage IIIa, IIIb, or IV disease. All of the 24 patients less than 40 years of age underwent thoracotomy: curative resection in 14 cases, palliative resection in sex, and probe-thoracotomy in four. The 5-year survival rate for all stages of disease was 31.4% in these 24 patients, and 41.9% in 603 patients greater than 40 years of age. The 5-year survival rate for stage I disease was 35.7% in the seven younger patients and 78.0% in the 207 older patients; for stage II, it was 25.5% in the four younger patients and 40.6% in the 98 older patients; for stage III, it was 33.3% in the nine younger patients and 15.6% in the 250 older patients; and for stage IV, it was 25% in the four younger patients and 6.6% in the 48 older patients. There were no significant differences in survival rate between the two age groups for all patients or for those with each stage of disease. CONCLUSION: Although younger patients tended to have more advanced disease, long-term survival in these patients did not differ from that of older patients.