Nonsecretory myeloma, immunoglobulin D myeloma, and plasma cell leukemia

Nonsecretory myeloma, which accounts for 1% to 5% of all myelomas, is characterized by the absence of detectable M-protein in serum and urine. The presenting features of nonsecretory myeloma are similar to those in patients with a detectable M-protein, except for the absence of renal function impairment. The response to therapy and survival of patients with nonsecretory myeloma are similar to those of patients with measurable M-protein. Immunoglobulin D myeloma represents 2% of all myelomas. Patients with IgD myeloma usually present with a small band or no evident M-spike on serum electrophoresis and heavy light-chain proteinuria. Thus, IgD myeloma can be considered a variant of Bence Jones myeloma; the presence of the IgD M-protein and the predominance of the lambda light chain are the only distinctive features. The median survival of patients with IgD myeloma is almost 2 years, with one fifth of them surviving for more than 5 years. Plasma cell leukemia is also a rare form of plasma cell dyscrasia (2% to 4% of all myelomas). The primary form accounts for 60% of the cases. In primary PCL, the constellation of adverse biologic prognostic factors in patients with advanced aggressive myeloma is already present at diagnosis. In fact, primary PCL has a more aggressive clinical presentation than MM, with a higher frequency of extramedullary involvement, anemia, thrombocytopenia, hypercalcemia, and renal failure. Treatment with a single alkylating agent plus prednisone is not appropriate. Combination chemotherapy with VAD, cyclophosphamide and etoposide, or VCMP/VBAP is a better initial option. Given the poor prognosis of primary PCL, intensification with high-dose therapy followed by stem cell rescue should be offered to affected patients.     

Alternating combination chemotherapy and levamisole improves survival in multiple myeloma: a Southwest Oncology Group Study

Previously untreated patients with multiple myeloma were entered on a randomized clinical trial to determine whether the use of alternating combination chemotherapy, including vincristine, doxorubicin, alkylating agents, and prednisone (160 patients) was more effective than conventional chemotherapy with melphalan and prednisone (77 patients), and whether the addition of the immunomodulating agent levamisole to maintenance chemotherapy enhanced the survival of patients achieving remission. The treatment groups were well matched for all major factors. The more aggressive chemotherapy was more effective at inducing remission, with a significantly higher proportion of patients achieving at least 75% tumor mass regression (53% with alternating combinations versus 32% with melphalan-prednisone, p = 0.002). Furthermore, the median survival was increased to 43 months with alternating combination chemotherapy as compared to 23 months with melphalan-prednisone (p = 0.004). After six to 12 months of induction therapy, 84 patients achieving remission were rerandomized to receive maintenance chemotherapy alone or with the addition of levamisole. The survival from the start of maintenance therapy was longer in patients receiving the added levamisole than with chemotherapy alone (p = 0.01). These findings support the use of aggressive multiagent chemotherapy for remission induction in patients with advanced-stage multiple myeloma.     

Cross-resistance to alkylating agents in multiple myeloma

In order to ascertain whether multiple myeloma patients resistant to one alkylating agent would respond to a second one, high-dose intermittent cyclophosphamide was administered to 12 patients showing resistance to melphalan and prednisone. On the other hand, intermittent melphalan and prednisone treatment was employed in eight myeloma patients resistant to intermittent cyclophosphamide. Only one objective response was achieved among 12 patients on cyclophosphamide therapy, in spite of having employed high doses of this alkylating agent. No responses were achieved with melphalan in the group of cyclophosphamide-resistant patients. The median survival probability was 8.7 months (SD +/- 2.9) for all patients after starting the second alkylating agent. These results suggest cross-resistance between melphalan and cyclophosphamide in myeloma. The authors conclude that a single second alkylating agent cannot be recommended as a treatment of patients with multiple myeloma who are truly refractory to one alkylating agent.     

Multiple myeloma. An update on diagnosis and management

Patients with multiple myeloma must be differentiated from those with monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). The plasma cell labeling index is helpful in differentiating MGUS or SMM from multiple myeloma (MM). No difference in survival was noted between patients given a single alkylating agent and those given a combination of alkylating agents. Alternating cycles of interferon alpha 2 and VBMCP (vincristine, BCNU, melphalan, cyclophosphamide, prednisone) produced a complete or near-complete response in 41% of patients. Allogeneic or syngeneic bone marrow transplantation has produced some benefit. Autologous bone marrow transplantation is potentially applicable to treat more patients. Major problems are eradication of myeloma cells from the bone marrow and removal of myeloma cells from autologous bone marrow. Purging of myeloma cells with monoclonal antibodies and chemotherapy may be helpful. Stem cells from autologous peripheral blood are being used for rescue after high-dose chemotherapy and total-body irradiation.     

Lack of Renal Recovery Predicts Poor Survival in Patients of Multiple Myeloma With Renal Impairment

BackgroundRenal impairment (RI) confers a poor prognosis in multiple myeloma. Reversibility of renal function is associated with improved survival in such patients. Patients in developing countries often present at an advanced stage and renal impairment is present in up to 40% of patients at diagnosis. We studied the renal outcome and survival of these patients with bortezomib-based induction therapy.Materials and MethodsIt was a single-center prospective study in a tertiary care multi-specialty institute in patients of newly diagnosed multiple myeloma (NDMM) who presented with RI from July 2018 to December 2019. The diagnosis of multiple myeloma was made based on IMWG14 criteria. All patients received bortezomib and or immunomodulatory drug-based triplet or quadruplet induction therapy. Hematological and renal outcomes were assessed as per IMWG 2016 criteria.ResultsAmong 216 consecutive patients of NDMM, RI was seen in 91 (42.2%) patients. The median age of 91 patients was 60 years. (range- 32-80 years). Light chain myeloma was seen in 26% (n = 24) of patients. The median estimated glomerular filtration rate (eGFR) was 15.36 mL/min (3.1-38 mL/min) and a majority of patients were in the advanced ISS stage. (ISS III = 85.7%). Thirty-six (39.5%) patients received hemodialysis at presentation. Renal response was seen in 67 (73%) patients and 20 (out of 36; 55%) became dialysis independent over a median time of 38 days (Range 15-160 days). At a median follow-up of 14.7 months, 30 (33%) patients had died, of which, 14 (15.4%) patients had early mortality (within 2 months of diagnosis). Presence of light chain myeloma and cast nephropathy (definite or probable) were identified as independent predictors of poor renal recovery on multivariate analysis. (HR = 2.841; 95% CI [1.471-5.486], P = .002 for light chain myeloma; HR = 1.859; 95% CI (1.087-3.180); P = .024 for cast nephropathy) Patients with low eGFR at presentation (<12.5 mL/min) were more likely to have persistent renal insufficiency. (HR-3.521; 95% CI (1.856-6.679), P = .000). Patients who attained sustained renal recovery had improved survival as compared to patients in whom renal function failed to improve. (median OS- not reached vs. 8.3 months, P = .000) Achievement of hematological response and independence from hemodialysis was associated with improved survival on multivariate analysis.ConclusionRenal impairment was reversible in almost three-fourths of NDMM patients. achievement of hematological response and hemodialysis independence were independent predictors of improved overall survival in NDMM patients with RI.     

Smoldering,asymptomatic stage 1, and indolent myeloma

Opinion statement Of patients presenting with multiple myeloma, 5% to 15% satisfy criteria for the diagnosis of multiple myeloma but have no or minimal symptoms and do not require chemotherapy (NRC). These patients are classified as having smoldering, asymptomatic stage 1, or indolent multiple myeloma in order of their increasing risk of progression. We avoid chemotherapy, especially with alkylating agents in such patients, and we either closely monitor them or use a nonchemotherapeutic intervention. If significant bone lesions, renal failure, or hypercalcemia occur, chemotherapy or transplant is recommended. Patients with mild anemia or with small or isolated bone lesions who are asymptomatic or minimally symptomatic because of anemia may be monitored and are classified as having indolent multiple myeloma. Unnecessary treatment with melphalan or cyclophosphamide probably has no benefit in multiple myeloma NRC and can cause significant risk. In long-term follow up, 25% of patients receiving alkylating agents develop myelodysplastic syndrome or acute leukemia. Patients who do not receive chemotherapy must be monitored closely to avoid complications of overt multiple myeloma, including anemia, bone lesions, renal failure, and hypercalcemia. We and others have begun to take a more active approach with the use of nonchemotherapeutic agents in selected patients. We use bisphosphonates in patients with bone lesions or osteoporosis or when there is a progressive rise in M-protein. We use dexamethasone alone in NRC multiple myeloma to reduce tumor burden in selected patients who do not yet have overt multiple myeloma or who are not candidates for chemotherapy. We use bisphosphonates to prevent osteoporosis in such patients. We use erythropoietin to correct anemia, and dexamethasone and erythropoietin together in patients with higher tumor burden (eg, indolent multiple myeloma). Future progress in treating multiple myeloma NRC depends on better identification of new therapeutic targets that control progression from the stable asymptomatic to the progressive symptomatic phase of multiple myeloma. We need to better understand the biologic target of new agents like thalidomide to design more effective treatment for this early phase of multiple myeloma. Although these approaches may delay chemotherapy, it is not known whether survival is prolonged. Nonchemotherapeutic approaches must be systematically studied in clinical trials in order to be put to better use.     

A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival.

The presenting clinical features of 71 patients with multiple myeloma were correlated with myeloma cell mass (myeloma cells X 10(12)/m2 of body surface area) determined from measurements of monoclonal immunoglobulin (M-component) synthesis and metabolism. Bivariate correlation and multivariate regression analyses showed that myeloma cell mass could be accurately predicted from A) extent of bone lesions, B) hemoglobin level, C) serum calcium level, and D) M-component levels in serum and urine. Analyses of response to chemotherapy and survival indicated significant correlation with measured myeloma cell burden. The results were synthesized to produce a very reliable and useful clinical staging system with three tumor cell mass levels (Table 7). For clinical research purposes, multivariate regression equations were developed to predict optimally the exact myeloma cell mass. Thus, initial staging can be quantitatively related to followup using tumor cell mass changes calculated from changes in M-component production. Use of the clinical staging system sould provide better initial assessment and followup of individual patients, and should lead to improved study design and analysis in large clinical trials of therapy for multiple myeloma.     

Eligibility for hematopoietic stem-cell transplantation for primary systemic amyloidosis is a favorable prognostic factor for survival.

PURPOSE: Based on the success of hematopoietic stem-cell transplantation (HSCT) for multiple myeloma, HSCT is being used to treat patients with primary systemic amyloidosis (AL). This article addresses the extent to which eligibility to undergo HSCT is a favorable prognostic feature and explores prognostic factors within the subset of eligible patients. PATIENTS AND METHODS: The Mayo Clinic amyloid database was queried for all patients with AL seen at the Mayo Clinic from 1983 through 1997 who would have been eligible for peripheral-blood stem-cell transplantation. Inclusion criteria included biopsy-proven amyloid, symptomatic disease, absence of a clinical diagnosis of multiple myeloma, age < or = 70 years, cardiac interventricular septal thickness < or = 15 mm, cardiac ejection fraction more than 55%, serum creatinine < or = 2 mg/dL, and direct bilirubin < or = 2.0 mg/dL. RESULTS: Median age was 56 years (range, 25 to 70) with 79 (34%) older than 60 years. One hundred patients had early cardiac involvement; 41, hepatic involvement; 167, renal involvement; and 39, nerve involvement. The 229 patients have had a median follow-up of 52 months, and 151 have died. The median survival was 42 months with 5- and 10-year survival rates of 36% and 15%, respectively. Important predictors of survival were size of M-component in 24-hour urine, number of involved organs, alkaline phosphatase, performance score, and weight loss. CONCLUSION: The same patients who are eligible for HSCT are a good-risk population who do relatively well with chemotherapy (median survival, 42 months), substantially better than the expected median survival of 18 months for all patients with AL. A randomized trial is needed to assess the true effect of HSCT.     

The disposition of cyclophosphamide in a group of myeloma patients

Summary The disposition of cyclophosphamide and its alkylating metabolites was investigated in a group of myeloma patients with varying degrees of renal function impairment. No correlation between renal function and clearance of cyclophosphamide or its alkylating metabolites was found. No evidence of accumulation of cyclophosphamide or alkylating activity was found in four patients receiving radiolabelled cyclophosphamide. Renal function was found to be related to the reciprocal of the area under curve of alkylating activity, indicating that this area increased as renal function decreased. In view of the large nonrenal component of alkylating activity elimination and the large inter-subject variability, it is recommended that dose of cyclophosphamide is not altered in moderate impairment of renal function.     

An Aggressive High Dose Cyclophosphamide and Prednisone Regimen for Advanced Multiple Myeloma

There is strong evidence that corticosteroids contribute to the objective and subjective response rate observed following treatment with several cytotoxic chemotherapy agents, and that there is a dose response effect for treatment of multiple myeloma with alkylating agents. Therefore, the Eastern Cooperative Oncology Group (ECOG) studied cyclophosphamide 600 mg/M² given for four consecutive days intravenously combined with prednisone 100 mg orally daily in 57 patients who had progressed following or failed to respond to standard doses of these drugs. Forty eight patients met the eligibility criteria for evaluation of response and toxicity. Fourteen patients (29%) had an objective response (OR) and an additional 2 (4%) had a subjective response (SR) only. The median duration of objective response was 3.1 months and estimated median survival was 8.6 months. These results are identical to our prior experience with high dose cyclophosphamide alone. The addition of prednisone does not appear to enhance results either through increased remissions or greater survival. Therefore, this study indicates that the preferred form of high dose cyclophosphamide for multiple myeloma is as a single agent given in intravenous four day courses.     

Determination of plasma cell secreting potential as an index of maturity of myelomatous cells and a strong prognostic factor

According to the widely accepted myeloma staging system, the bulk of paraprotein is the main determinant of disease stage. However, myelomatous plasma cells differ considerably in their ability to synthesize and secrete monoclonal paraprotein. We determined plasma cell secreting potential (PCSP) as the amount of M-component, divided by the percentage of marrow plasmacytic infiltration, in 240 patients with myeloma, and correlated our results with chain isotype, plasma cell morphology, severity of bone disease, well-recognized prognostic factors, such as serum LDH, CRP, albumin and beta2-microglobulin, treatment response and overall survival. PCSP was higher in IgG than in other myeloma types, and was an almost constant parameter for each individual patient, in 134/166 cases. A > 10% decrease of PCSP in 26 patients was associated with disease aggressiveness and treatment failure. Patients with MGUS had significantly higher PCSP than those with myeloma of the same chain type. Higher PCSP was associated with stage I, absence of Bence-Jones proteinuria and indolent forms of disease with lower proliferating cell nuclear antigen (PCNA) positivity, serum LDH, alpha2-globulins, CRP and beta2-microglobulin and higher albumin levels. Conversely, patients with immature/plasmablastic morphology and those with severe bone disease had lower PCSP. Good responders to treatment had significantly higher PCSP than moderate and poor responders and PCSP was strongly correlated with overall survival in IgG and IgA myeloma. In conclusion, PCSP reflects the maturation status of myelomatous cells and therefore can be used as a prognostic factor, since patients with high secreting potential represent a lower malignancy group, in comparison to those with a low secreting potential.     

脊柱浆细胞骨髓瘤中骨桥蛋白的表达及其临床意义

目的:探讨脊柱浆细胞骨髓瘤（plasma cell myeloma,PCM）中骨桥蛋白(osteopontin,OPN)的表达及其与临床病理特征和预后的相关性。方法：选取第二军医大学长征医院19982006年间41例脊柱PCM及14例脊柱良性单纯性骨囊肿手术切除标本;应用免疫组织化学链霉菌抗生物素蛋白过氧化物酶连结（SP）法检测OPN的表达。结果：（1）OPN在脊柱PCM中的阳性表达率为82.93%(34/41) ,而良性骨囊肿中OPN表达均呈阴性 (P<0.01);（2）脊柱PCM中OPN蛋白的表达程度在M蛋白分型和临床分型各组之间差异均有统计学意义（P<0.05）,而与患者轻链分型、病理形态学分级、年龄和性别无显著关联（P>0.05）;（3）OPN表达阳性患者整体生存率明显高于阴性组(P<0.01)。结论：OPN表达阴性脊柱PCM患者的预后可能较差。联合检测OPN和M蛋白分型以及临床分型对脊柱PCM预后判断可能有一定的临床意义。     

平阳霉素诱导化疗在T2舌鳞癌治疗中的应用价值

背景与目的：诱导化疗在舌鳞癌治疗中具有重要作用,本研究目的在于探讨单药平阳霉素诱导化疗在T2舌鳞癌治疗中的应用价值。方法：回顾性分析单纯手术及单药平阳霉素诱导化疗加手术分别治疗36例舌鳞癌T2病变患者后,对其生存及复发情况的影响。结果：单纯手术组及诱导化疗加手术组的5年生存率分别为81.46％和57.14％,差异有显著性（P=0.0299）;区域/局部复发率分别为22.2％和33.3％,中位复发时间分别为20和24个月。对Ⅱ、Ⅲ期及Ⅳ期患者,两种治疗措施的5年生存率无显著差异（P=0.0949;P=0.0939）。在Ⅲ及Ⅳ期病变中,单纯手术组和诱导化疗加手术组的区域/局部复发率分别为12.5％和35.7％,中位复发时间分别为12和12.8个月。结论：单药平阳霉素诱导化疗对舌鳞癌T2病变的治疗价值不大。不管是早T2病变还是晚T2病变,它对患者的5年生存率没有明显影响,对局部控制率的影响仍有待进一步观察。     

肾功能衰竭行替代治疗的肿瘤患者化疗疗效和不良反应

目的分析合并肾功能衰竭并需要行替代治疗的恶性肿瘤患者临床特点、化疗疗效和对患者生存的影响。方法选取合并肾功能衰竭并需要行替代治疗的恶性肿瘤患者，分析其所采用的化疗方案、药物的剂量强度、有效率和对患者生存的影响及其不良反应。结果共22例肾功能衰竭合并替代治疗患者进行化疗，其中骨髓瘤患者10例，非骨髓瘤患者12例。骨髓瘤合并肾功能衰竭行替代治疗患者化疗平均剂量强度为标准剂量的91±19．12％，化疗有效率为87．5％，6个月、1年、2年和3年生存率分别达到80％、60％、不低于25％和不低于12．5％。3例患者肾功能好转。非骨髓瘤患者化疗平均剂量强度为标准剂量的82．55±17．73％，行辅助化疗患者6个月、1年和2年无病生存率分别为83．33％，不低于60％和不低于40％。晚期患者化疗有效率为80％，6个月、1年、2年和3年生存率分别为83．33％、不低于80％，不低于40％和不低于20％。常见的不良反应：Ⅲ-Ⅳ度骨髓抑制发生率为18．18％，感染率发生率为31．82％。结论合并肾功能衰竭并需要行替代治疗的恶性肿瘤患者可以进行化疗并获得一定的长期生存，医师需要根据药物的代谢特点和患者个体化需求进行剂量调整并监测不良反应。     

Three cases of multiple myeloma in which the preclinical asymptomatic phases persisted throughout 15 to 24 years

During the period from 1950 to 1952, three patients were studied by electrophoresis according to Tiselius on account of anticomplementary activity at WR; the presence of an M-component was demonstrated. On several later occasions it was observed that this component at first seemed to remain unchanged, later it was slightly increased; repeated examinations did not give evidence of multiple myeloma. At intervals ranging from 15 to 24 years after the primary demonstration of the M-component, all three patients presented with symptoms of multiple myeloma and died within less than one year after the disease had been diagnosed. The following conclusions are drawn:     

多发性骨髓瘤肾脏病变的研究进展

 多发性骨髓瘤（MM）患者肾损害谱包括"骨髓瘤肾"或管型肾病、轻链淀粉样变、单克隆免疫球蛋白沉积病、冷球蛋白血性肾小球肾炎和增生性肾小球肾炎等。MM肾脏病患者肾活组织病理检查研究显示,管型肾病占40 %～63 %,肾轻链沉积病（LCDD）占19 %～26 %,淀粉样变占7 %～30 %,冷球蛋白肾病＜1 %。管型肾病、MIDD和淀粉样变的肾病理学不同。骨髓瘤相关肾病的肾外表现较多样,进展为肾功能不全和末期肾病（ESRD）发生率高,并发症增加,死亡率显著升高,合并肾病的MM患者生存期和肾生存期短。治疗包括MM化疗、血液透析和自体造血干细胞移植（ASCT）等,ASCT有血液学反应和肾反应者的生存率明显改善,成功的ASCT给更多的患者以肾和其他脏器移植的机会。     

Adjuvant Chemotherapy and Prognostic Factors in Stage II Colon Cancer - Izmir Oncology Group Study

Background: Although adjuvant chemotherapy is a standard treatment in stage III colon cancer, its benefitis not as clear for stage II patients. In this retrospective analysis, we aimed to evaluate the survival of patientswith low-risk stage II colon cancer, the efficacy of adjuvant chemotherapy in high-risk stage II colon cancerpatients, and prognostic factors in stage II disease. Materials and Methods: One hundred and seventeen patientswho were diagnosed with stage II colon cancer between January 2006 and December 2011 were included inthe study. Patients were stratified into two groups as being low-risk and high-risk according to risk factorsfor stage II disease. Adjuvant 5-fluorouracil-based chemotherapy were administered to the patients with riskfactors. Results: Ninety-four patients were treated with adjuvant chemotherapy due to high risk factors and 23were monitored without treatment. Median follow-up time was 43 months. In terms of disease free survival andoverall survival, adjuvant chemotherapy did not provide a statistically significant difference. Univariate analysisdemonstrated that bowel obstruction was the major risk factor for shortened disease-free survival, while bowelperforation and perineural invasion were both negative prognostic factors for overall survival. Conclusions:The recommendation of adjuvant chemotherapy for stage II colon cancer is not clear. In our study, it was foundthat adjuvant chemotherapy did not contribute to survival in high-risk stage II patients. Due to the fact thatprognosis of stage II patients is good, many more patients will be needed for statistically significant differences insurvival. Adjuvant chemotherapy containing 5 fluorouracil is being used to high-risk stage II patients althoughit is not a standard treatment approach.     

Peripheral Blood Lymphocyte Surface Antigen Expression and Prognosis in Myeloma: Australian Leukaemia Study Group Study

The Australian Leukaemia Study Group myeloma study (MM1) aimed to determine the prognostic significance of clinical and immunophenotypic markers in patients with multiple myeloma. All patients were treated with standard dose melphalan and prednisone. Seventy-four patients were entered and the median survival was 27 months. Serum beta 2-microglobulin (βM) and albumin levels were the only significant clinical factors influencing survival (p = 0.007 and p = 0.008, respectively). Patients with raised levels of CD38+ lymphocytes at presentation had a significantly shorter survival than patients with normal levels (p = 0.01, logrank test, median 19 months vs 33 months). CD38 antigen expression was independent of β2M but patients with raised levels of CD38 had significantly lower levels of albumin than patients with normal levels (p = 0.001) which may explain their poorer survival. Salmon and Durie stage was not associated with antigen expression. No other B-cell antigens (CD10, CD19, CD20, CD21, CD22, CD23, FMC1 or FMC7) or plasma cell antigens tested (PCA-1) were found to be associated with prognosis. Patients who achieved plateau phase had a better prognosis than those who did not (p = 0.04 in a landmark analysis). Patients who achieved plateau phase following an objective response appeared to have a better prognosis than those who were in plateau phase at presentation (p = 0.09 in a landmark analysis). Light chain isotype suppression (LCIS) was not associated with a significant survival advantage and did not correlate with any known prognostic indicator. We conclude that phenotypic analysis of peripheral blood lymphocytes for CD38 antigen at diagnosis may be useful as a prognostic indicator in patients with myeloma.     

Prognostic factors in FIGO stage IB-IIA small cell neuroendocrine carcinoma of the uterine cervix treated surgically: results of a multi-center retrospective Korean study.

BACKGROUND: To determine the clinical and pathologic prognostic factors in surgically treated patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB-IIA small cell neuroendocrine carcinoma of the uterine cervix (SCNEC). PATIENTS AND METHODS: We retrospectively reviewed a total of 68 patients with FIGO stage IB-IIA SCNEC surgically treated from January 1997 to December 2003 in Korea. RESULTS: Of the 68 patients, 43 had FIGO stage IB1 SCNEC, 15 had stage IB2, and 10 had stage IIA. Seven were treated with radical surgery alone; 11 with neoadjuvant chemotherapy (NACT) followed by radical surgery; 24 with radical surgery followed by adjuvant chemotherapy; and 26 with radical surgery followed by adjuvant radiation or chemoradiation. After a median follow-up of 44 months (range, 6-113 months), the 2-year and 5-year survival rates for all patients were 64.6% and 46.6%, respectively. Univariate and multivariate analysis showed that FIGO stage was predictive of poor prognosis. Patients who received NACT showed poorer prognosis than those who did not receive NACT. Adjuvant chemoradiation did not improve survival compared with adjuvant chemotherapy alone. CONCLUSIONS: FIGO stage may act as a surrogate for factors prognostic of survival. Primary radical surgery followed by adjuvant chemotherapy is the preferred treatment modality for patients with early stage SCNEC.     

Adjuvant chemotherapy of cancer of the ovary

The aim of adjuvant chemotherapy is to cure micrometastatic disease and to prevent relapses after apparently complete surgical exeresis. It is almost always administered after initial surgical treatment, except for stage IA1 malignant epithelial tumours and stage I-II pur dysgerminomas. Chemotherapy combines anthracycline, an alkylating agent, a plant alkaloid and cis-platinum, for 4-8 months. After second-look laparotomy, if no more macro or microscopic tumor have been discovered, adjuvant chemotherapy does not seem necessary. However it is when all residual tumor has been excised or cyto- and/or histologic controls are positive. Optimal schedules are not yet perfectly defined. In some cases, a third look laparotomy should confirm the absence of tumor in order to stop treatment. Side effects (hematologic, gastrointestinal, neurologic, renal) are frequent. It is necessary to recognize patients able to benefit from chemotherapy and to define the least toxic treatment.