Correlation of clinical and pathologic features with outcome in patients with ductal carcinoma in situ of the breast treated with breast-conserving surgery and radiotherapy

: Although breast-conserving surgery followed by radiotherapy (RT) has become a standard treatment option for patients with ductal carcinoma in situ of the breast, risk factors for ipsilateral breast tumor recurrence (IBTR) in these patients remain an active area of investigation. The purpose of this study was to evaluate the impact of clinical and pathologic features on long-term outcome in a cohort of DCIS patients treated with breast-conserving surgery plus RT.

: Between 1973 and 1998, 230 patients with DCIS were treated with breast-conserving surgery plus RT at our institution. All patients were treated by local excision followed by RT to the breast to a total median tumor bed dose of 64 Gy. Adjuvant hormonal therapy was used in only 20 patients (9%). All available clinical, pathologic, and outcome data, including ipsilateral and contralateral events, were entered into a computerized database. The clinical and pathologic variables evaluated included detection method, mammographic appearance, age, family history, histologic subtype, presence of necrosis, nuclear grade, final margin status, and use of adjuvant hormonal therapy.

: As of December 15, 2000, with a median follow-up of 8.2 years, 17 patients had developed a recurrence in the ipsilateral breast, resulting in a 5- and 10-year IBTR rate of 5% and 13%, respectively. Contralateral breast cancer developed in 8 patients, resulting in a 10-year contralateral recurrence rate of 5%. Patient age, family history, histologic subtype, margin status, and tumor grade were not significantly associated with recurrence on univariate analysis. A significantly higher rate of local relapse was observed in patients with the presence of necrosis. The 10-year relapse rate was 22% in 88 patients with necrosis compared with 7% in 142 patients without necrosis (p <0.01). In multivariate analysis, the presence of necrosis remained a significant predictor of local relapse. No breast relapses occurred among the 8 patients with positive margins, and three relapses developed among 21 patients with close margins. The rate of IBTR in those with close/positive margins did not differ from the rate in those with negative or unknown margins. It is also notable that none of the 20 patients treated with adjuvant tamoxifen had developed IBTR or a contralateral event to date, although the follow-up on this group was still too short to reach significance.

: In this cohort of uniformly treated patients with a relatively long follow-up, the presence of necrosis was a significant predictor of local relapse. However, positive or close margin status was not a significant predictor of local relapse. Although none of the patients receiving tamoxifen had a recurrence in the ipsilateral or contralateral breast, longer follow-up is required to assess the effect of tamoxifen on these end points.     

盖诺联合顺铂治疗恶性肿瘤近期疗效观察

目的　观察盖诺与顺铂治疗恶性肿瘤的疗效及毒副作用。方法　采用NP(盖诺 2 5mg/m2 d1 ,8加顺铂 5 0mgd1～ 3 )方案治疗恶性肿瘤 3 2例 ,其中非小细胞肺癌 16例 ,乳腺癌 10例 ,食管癌 6例 ,化疗 2～ 4周期后评价疗效。结果　CR 3例 ,PR 13例 ,NC 11例 ,PD 5例 ,总有效率为 5 0 %,其中NSCLC有效率 43 8%,乳腺癌 60 %,食管癌 5 0 %,主要毒副作用为骨髓抑制及恶心呕吐。结论　NP方案治疗恶性肿瘤疗效较好 ,毒副作用可耐受     

Excretion of nitrates with saliva and urine and nitrite excretion with saliva in patients with chronic gastritis and duodenal ulcer

The study assessed excretion of nitrates in urine and saliva and that of nitrites with saliva of patients suffering gastric and duodenal ulcer. In both study groups, a positive correlation was established between nitrate concentration in saliva, on the one hand, and that in urine, and nitrite level in urine, on the other. The groups failed to show a difference in nitrate concentrations in either urine or saliva. Since retention of nitrates in the body of chronic gastritis patients held as precancer of the stomach proved no higher than that in patients with duodenal ulcer, the authors cast doubt on endogenous nitroso compounds as a cause of gastric cancer in cases of chronic gastritis.     

Metabolism of chylomicron-like emulsions in patients with Hodgkin's and with non-Hodgkin's lymphoma

BACKGROUND: Chylomicrons carry in the bloodstream dietary fats absorbed the intestine for storage in the body tissues such as adipose and muscle. The two-step chylomicron metabolism consists in lipolysis by lipoprotein lipase on vessel walls and hepatic uptake of triglyceride-depleted remnants. Chylomicron metabolism is understudied in cancer, despite its direct involvement in the patient nutritional status. We investigated this metabolism in Hodgkin and non-Hodgkin lymphoma patients, using the method of triglyceride-rich emulsions that mimic chylomicrons. PATIENTS AND METHODS: The chylomicron-like emulsion, labeled with [9,10-3H]glycerol-trioleate and [1-14C] cholesteryl-oleate was intravenously injected into 11 Hodgkin's, 19 non-Hodgkin's patients and 12 healthy subjects. Triglyceride kinetics evaluate lipolysis whereas cholesteryl ester kinetics evaluate remnant removal. RESULTS: Plasma total, LDL, HDL cholesterol, apo B, apo A1 and Lp(a) values were similar between the three groups, but VLDL cholesterol and triglycerides were higher in the lymphoma groups. The fractional catabolic rate (FCR, in min(-1)) of the emulsion triglycerides was roughly three-fold smaller in non-Hodgkin's (0.043+/-0.007, mean+/-S.E.M., P<0.001) and Hodgkin's (0.045+/-0.009, P<0.0001) lymphoma patients compared with the control values (0.151+/-0.032). FCR of the emulsion cholesteryl esters, was four-fold smaller in non-Hodgkin's (0.016+/-0.002, P<0.0001), and three-fold in Hodgkin's lymphoma patients (0.024+/-0.006, P<0.001) compared with the control group (0.069+/-0.013). The lipolysis index, calculated from the decay curves of both isotopes was also markedly smaller in both groups of lymphoma patients compared with the controls. CONCLUSIONS: In both lymphoma groups, marked alterations in chylomicron lipolysis and remnant removal occurs.     

Assessment of guilt and shame in patients with non-small-cell lung cancer compared with patients with breast and prostate cancer

PURPOSE: Patients with lung cancer might feel more guilt and shame resulting from previous smoking. This study was designed to determine the levels of guilt and shame among patients with non-small-cell lung cancer (NSCLC) compared with breast and prostate cancer. PATIENTS AND METHODS: Surveys were sent to participants 3 times (at enrollment, 2 months, and 6 months). Patients were eligible if they had stage IV NSCLC, breast cancer, or prostate cancer. The survey included tests of generalized guilt, shame, depression, and anxiety as well as guilt, shame, and embarrassment related to one's cancer. RESULTS: One hundred seventy-two participants completed >or= 1 questionnaire: 96 patients with NSCLC, 30 patients with breast cancer, and 46 patients with prostate cancer. Of the patients with NSCLC, 91.7% were current or former smokers versus 67.1% of the comparison patients. A composite score of embarrassment related to one's cancer (perceived cancer-related stigma; PCRS) was higher in patients with NSCLC (P < .01). Mean baseline generalized guilt and shame scores were not different among groups and did not change over time. A history of smoking correlated with increased levels of guilt and shame, regardless of tumor type. A personal identification of past behaviors as contributing to cancer correlated with higher levels of guilt, shame, anxiety, and depression. Of the patients with NSCLC, 29.5% felt that their behaviors contributed to their cancer compared with 10.5% of the comparison patients. CONCLUSION: Patients with NSCLC had higher levels of PCRS than patients with prostate cancer or breast cancer but not higher baseline levels of shame and guilt. Smoking is correlated with higher levels of guilt and shame. A belief that one caused one's own cancer is correlated with higher levels of guilt, shame, anxiety, and depression. These findings could be translated into an increased need for open communication among patients and their providers surrounding issues of cancer causation, guilt, shame, depression, and anxiety.     

Prevention and management of osteoporosis in women with breast cancer and men with prostate cancer

Advances in cancer treatment have resulted in improved life expectancies for survivors of breast and prostate cancer. As the number of cancer survivors grows, the long-term side effects of treatment play an increasingly prominent role in the routine care of these patients. Due to similar management approaches, survivors of breast and prostate cancer are at increased risk for osteoporosis. This review summarizes the prevention and management of osteoporosis and osteopenia resulting from cancer treatment in survivors of breast and prostate cancer.     

Treatment with antioxidant and other nutrients in combination with chemotherapy and irradiation in patients with small-cell lung cancer.

Eighteen non-randomized patients with small cell lung cancer (4 women and 14 men, mean age 60.4, SD 7.8 years) received in addition to conservation small cell lung cancer treatment antioxidant treatment with vitamins, trace elements and fatty acids. All patients were out-patients who, except for one were also treated with chemotherapy and/or irradiation at regular intervals at a university of central hospital. Five patients (28%) were in an advanced stage of the disease. At the end of the follow-up period (31.7.90) the median survival time for the whole group was 505 days. Fourteen (77%) of the patients survived for more than 12 months and six patients (33%) for more than two years. One patient (5%) survived more than five years. Eight patients (44%) were still alive with a mean survival time of 32 months at the end of the study. Ten patients succumbed earlier from progression of the disease. Antioxidant treatment, in combination with chemotherapy and irradiation, prolonged the survival time of patients with small cell lung cancer compared to most published combination treatment regimens alone. We also noticed that the patients receiving antioxidants were able to tolerate chemotherapy and radiation treatment well. Surviving patients started antioxidant treatment in general earlier than those who succumbed.     

Compliance with guidelines and correlation with outcome in patients with advanced germ-cell tumours

PurposeTo evaluate prior compliance with guidelines in patients treated with salvage chemotherapy for advanced germ-cell tumours (GCT).Patients and methodsData concerning the initial management of patients requiring salvage chemotherapy for GCT at Institut Gustave Roussy between 2000 and 2010 were obtained and correlated with recommendations for treatment. Criteria of non-compliance were defined based on guidelines. Compliance with guidelines, predictive factors for non-compliance and the impact on outcome were analysed.ResultsAmong 82 patients treated in the salvage setting, guidelines to initial treatment were followed in only 41 cases (50%). The most common non-compliance criteria were non-adherence to the planned dose (16%), an inappropriate interval between first-line chemotherapy cycles (16%), the lack of post-chemotherapy surgery (16%) and a long interval to post-chemotherapy surgery (48%). Compliance with standard care was better in cancer centres than in other hospitals (private or public) (Odd Ratio (OR): 6.9, P = 0.001). A poor-risk status according to the International Germ Cell Cancer Collaborative Group (IGCCCG) was also predictive of compliance in univariate but not in multivariate analysis. No significant difference in outcome after salvage chemotherapy was observed. Patients relapsing after non-compliant first-line therapy tended to be more easily salvaged, which is consistent with the fact that their initial treatment was inadequate. Some of these relapses were therefore probably not due to true biologically refractory disease.ConclusionGuidelines for first-line treatment are adhered to in only half the patients requiring salvage chemotherapy. As the only predictive factor for non-compliance was the treating centre, centralisation of patients with GCT in well-trained hospitals should be recommended.     

Safety and activity of masitinib in combination with gemcitabine in patients with advanced pancreatic cancer

Purpose

To evaluate the efficacy and safety of masitinib combined with gemcitabine in patients with advanced pancreatic cancer.

Patients and methods

Twenty-two non-randomised patients with unresectable, locally advanced (n = 9) or metastatic pancreatic cancer (n = 13) received oral masitinib (9 mg/kg/day) combined with standard gemcitabine. All patients were na?ve to systemic chemotherapy or radiotherapy. The primary endpoint was time-to-progression (TTP) with efficacy and safety analyses performed on the intent-to-treat population. Secondary endpoints included overall survival (OS), as well as, subgroup analyses according to baseline disease, and performance status.

Results

Overall median TTP was 6.4 months (95% CI [2.7–11.7]); 8.3 and 2.7 months, respectively, for locally advanced and metastatic patients; 6.4 and 0.8 months, respectively, for patients with KPS [80–100] or KPS [70]. Median OS was 7.1 months (95% CI [4.8–17.0]); 8.4 and 6.8 months for locally advanced or metastatic patients, respectively; 8.0 and 4.4 months in patients with KPS [80–100] or KPS [70], respectively. The 18-month observed survival rate was similar for locally advanced (22%) and metastatic patients (23%) and reached 28% for KPS [80–100] patients. The most common suspected adverse events were nausea, vomiting, rash, diarrhoea, peripheral oedema, anaemia, lymphopenia, thrombocytopenia, pyrexia, neutropenia, asthenia, leucopoenia, and abdominal pain, and most were of grades 1–2 severity.

Conclusions

The efficacy and safety of masitinib combined with gemcitabine are encouraging, with extended survival and median TTP that support initiation of a phase 3 trial.     

Dose escalation study of nedaplatin with 5-fluorouracil in combination with alternating radiotherapy in patients with head and neck cancer

BACKGROUND: This study, with a large number of patients, confirms that after administration of 5-fluorouracil (5FU), a higher dose of nedaplatin (NDP) can be safely administered rather than a single therapy of NDP, as demonstrated in a phase I study. METHODS: The subjects were 52 patients with stage II-IV (M0) head and neck cancer other than nasopharyngeal cancer. Alternating chemoradiotherapy was performed using the following method. Initially, chemotherapy was administered. For chemotherapy, 5FU at 700 mg/m2/24 h was intravenously administered for 5 days (days 1-5), and NDP was administered on day 6. We established three dose groups: level 1, 120 mg/m2; level 2, 140 mg/m2; and level 3, 150 mg/m2 (n = 13 or more per group). RESULTS: The maximum acceptable dose of NDP (150 mg/m2) was confirmed. The 5-year overall survival rates were 77% (95% CI: 66-90%) in all subjects and 75% (95% CI: 61-92%) in the stage III/IV patients. The 5-year progression-free survival rates were 73% (95% CI: 62-87%) in all subjects and 72% (95% CI: 57-89%) in the stage III/IV patients. CONCLUSIONS: After administration of 5FU, a higher dose of NDP can be safely administered. This alternating chemoradiotherapy showed potent antitumor effects. The efficacy of chemotherapy with NDP and 5FU should be compared to that of chemotherapy with CDDP and 5FU.     

消化系统肿瘤及炎症患者血清TSGF的检测及临床意义

目的　评价血清肿瘤相关物质 (TSGF)在消化系统恶性肿瘤诊断中的临床意义。方法　以正常人、急或慢性消化系统炎症和消化系统良性肿瘤患者作对照 ,测定了多种消化系统恶性肿瘤患者血清TSGF的含量。结果　各种恶性肿瘤患者之间血清TSGF的水平无显著性差异 (P >0 .0 5 ) ,但均明显高于正常人组、慢性炎症组及良性肿瘤组 (P <0 .0 1) ,而与急性炎症组无显著性差别 (P >0 .0 5 )。结论　TSGF是鉴别良性和恶性肿瘤的可靠指标 ,对消化系统恶性肿瘤的诊断有一定的临床价值。     

紫杉醇联合奥沙利铂与紫杉醇联合顺铂治疗老年晚期非小细胞肺癌疗效观察（附72例）

目的：观察和比较紫杉醇（PTX）联合奥沙利铂（L—OHP）与紫杉醇联合顺铂（DDP）治疗老年晚期非小细胞肺癌的疗效及不良反应。方法：经病理组织学或细胞学确诊为晚期非小细胞肺癌的老年患者（年龄≥70岁）72例为研究对象,分为紫杉醇联合奥沙利铂（PO）组及紫杉醇联合顺铂（PC）组,紫杉醇给予周剂量60mg／m^2,第1、8、15天静脉滴注3h,紫杉醇用药前1h、30min分别静推地塞米松10mg,用药前30min肌注非那根25mg,静滴西米替丁doing以预防过敏反应;奥沙利铂65mg／m^2,第1、8天静脉滴注2h;顺铂25mg／m^2,第1—3天静脉滴注;28天为1周期,每例患者至少治疗2周期以上,按照RECIST标准评价疗效和不良反应。结果：PO组35例：完全缓解（CR）1例,部分缓解（PR）10例,稳定（sD）14例,总有效率为31．4％;PC组37例：完全缓解0例,部分缓解10例,稳定13例,总有效率为27．0％;最常见的不良反应为骨髓抑制、消化道反应、肾功能损害、神经毒性等,其中P0组的神经毒性发生率显著高于PC组;PC组Ⅲ-Ⅳ度胃肠道反应和肾毒性显著多于PO组。结论：PO方案与PC方案治疗老年晚期非小细胞肺癌的疗效相似,但PO方案较PC方案的不良反应轻,老年患者更容易耐受,是老年晚期非小细胞肺癌较理想的化疗方法。     

Rituximab in combination with fludarabine and cyclophosphamide in the treatment of patients with recurrent follicular lymphoma

BACKGROUND: The current study was conducted to asses the safety profile and clinical activity of rituximab in combination with fludarabine and cyclophosphamide in patients with recurrent follicular lymphoma (FL). METHODS: This study was a noncomparative, multicenter, phase II study. Between March 2000 and December 2002, 54 patients with recurrent FL were enrolled in the FC+R trial. Patients received fludarabine at a dose of 25 mg/m(2) and cyclophosphamide at a dose of 300 mg/m(2) daily for 3 consecutive days, every 3 weeks for 4 cycles. Rituximab was administered at a dose of 375 mg/m(2) beginning 2 weeks after the first course of fludarabine and cyclophosphamide and then on Day 1 of each cycle thereafter. The planned treatment duration was 10 weeks. RESULTS: Overall, 92% of patients completed the planned therapy in 10 to 14 weeks and 74% achieved a complete response (CR). Among patients with BCL2-positive bone marrow, 86% obtained a molecular disease remission (MR). The median survival from treatment (SFT), the duration of disease remission (DR), and time to disease progression (TTP) had not been reached after a median follow-up of 45 months. Of the baseline characteristics, >2 previous treatments, BCL2-positive bone marrow, and low Follicular Lymphoma International Prognostic Index (FLIPI) score were found to be associated with better DR and/or TTP. Hematologic toxicity was transient and reversible, with the exception of 3 patients with severe and prolonged neutropenia. Three patients presented with infections, 1 of whom died of bronchopneumonia. CONCLUSIONS: The FC+R scheme, a nonanthracycline-containing regimen lasting up to 10 weeks, was found to be relatively well-tolerated and demonstrated significant antilymphoma activity with excellent clinical CR and molecular response rates.     

紫杉醇联合奥沙利铂与紫杉醇联合顺铂治疗老年晚期非小细胞肺癌疗效观察(附72例)

目的:观察和比较紫杉醇(PTX)联合奥沙利铂(L-OHP)与紫杉醇联合顺铂(DDP)治疗老年晚期非小细胞肺癌的疗效及不良反应.方法:经病理组织学或细胞学确诊为晚期非小细胞肺癌的老年患者(年龄≥70岁)72例为研究对象,分为紫杉醇联合奥沙利铂(PO)组及紫杉醇联合顺铂(PC)组,紫杉醇给予周剂量60mg/m2,第1、8、15天静脉滴注3h,紫杉醇用药前1h、30min分别静推地塞米松10mg,用药前30min肌注非那根25mg,静滴西米替丁40mg以预防过敏反应;奥沙利铂65 mg/m2,第1、8天静脉滴注2h;顺铂25 mg/m2,第1-3天静脉滴注; 28天为1周期,每例患者至少治疗2周期以上,按照RECIST标准评价疗效和不良反应.结果:PO组35例:完全缓解(CR)1例,部分缓解(PR)10例,稳定(SD)14例,总有效率为31.4%; PC组37例:完全缓解0例,部分缓解10例,稳定13例,总有效率为27.0%;最常见的不良反应为骨髓抑制、消化道反应、肾功能损害、神经毒性等,其中PO组的神经毒性发生率显著高于PC组;PC组Ⅲ-Ⅳ度胃肠道反应和肾毒性显著多于PO组.结论:PO 方案与PC方案治疗老年晚期非小细胞肺癌的疗效相似,但PO方案较PC方案的不良反应轻,老年患者更容易耐受,是老年晚期非小细胞肺癌较理想的化疗方法.     

Pharmacokinetic and pharmacodynamic analysis of combined chemotherapy with carboplatin and cyclophosphamide in patients with gynecological cancers

Background. This study was conducted to assess the utility of pharmacokinetic and pharmacodynamic analyses of chemotherapy with carboplatin (CBDCA) and cyclophosphamide (CPA). Methods. The pharmacokinetics (PK) and pharmacodynamics (PD) of chemotherapy with CBDCA and CPA were analyzed in 14 patients (12 with ovarian cancers and 2 with uterine cancers). The PD model based on myelosuppression was assessed in terms of concentrations of free platinum (free-Pt) and total CPA in blood samples. CBDCA (300 mg/m²) was administered intravenously (iv) over 1 h, and CPA (500 mg/m²) over 2 h. Free-Pt and CPA concentrations in blood samples were measured at several time points thereafter. Results. The nadirs of leukocyte and platelet counts were closely correlated with the free-Pt concentration 24 h after infusion (Pt-24), and with the CPA concentration 5 h after infusion (CPA-5). A PD model corresponding to the nadirs of leukocyte and platelet counts was thus generated. Conclusion. This PD model allowed ready prediction, from Pt-24 and CPA-5, of the degree of myelosuppression, a dose-limiting toxicity, for combined CBDCA and CPA chemotherapy. Received: June 19, 1997 / Accepted: July 27, 1998     

Phase II study of pomalidomide in combination with prednisone in patients with myelofibrosis and significant anemia

We evaluated pomalidomide with prednisone for myelofibrosis (MF) with significant anemia (hemoglobin < 10 g/dL). Patients (n = 29; 18 RBC-transfusion dependent) received 0.5 mg pomalidomide daily in continuous 28-day cycles with prednisone given for the first 3 cycles only. Six (21%) patients responded (median response duration 11.4 months), including four who achieved RBC-transfusion-independence per the Delphi criteria and two who achieved clinical improvement (in platelets and spleen, respectively) per the International Working Group for Myelofibrosis Research and Treatment criteria. Grade 3 toxicity occurred in 1 patient (fatigue). Pomalidomide with prednisone is safe therapy with modest activity in patients with MF and anemia.