FDG-PET for detection of recurrences from malignant primary bone tumors: comparison with conventional imaging.

BACKGROUND: The aim of this study was to assess the diagnostic ability of positron emission tomography using 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG-PET) in the detection of recurrences from malignant primary bone tumors compared with conventional imaging. PATIENTS AND METHODS: In 27 patients (6 osteosarcomas, 21 Ewing's sarcomas), 41 FDG-PET examinations performed for diagnosis or exclusion of recurrent disease were evaluated. Conventional imaging techniques consisted of magnetic resonance imaging of the primary tumor site, thoracic computed tomography, and Tc-99m methylene diphosphonate bone scintigraphy. The reference methods were the histopathological analysis and/or the clinical and imaging follow-up. RESULTS: In 25 examinations reference methods revealed 52 sites of recurrent disease (local n = 7; distant: osseous n = 22, pulmonary n = 13, soft tissue n = 10). On an examination-based analysis FDG-PET had a sensitivity of 0.96, a specificity of 0.81 and an accuracy of 0.90. Corresponding values for conventional imaging were 1.0, 0.56 and 0.82. CONCLUSIONS: The sensitivity, specificity and accuracy of FDG-PET in the detection of recurrences from osseous sarcomas are high. On an examination-based analysis, FDG-PET had a not significantly lower sensitivity in comparison with conventional imaging. However, FDG-PET showed a small advantage in the detection of osseous and soft-tissue recurrences compared with conventional imaging.     

Early detection of recurrence by 18FDG-PET in the follow-up of patients with colorectal cancer

We assessed the potential benefits of including systematic 18fluorodeoxyglucose positron emission tomography (FDG-PET) for detecting tumour recurrence in a prospective randomised trial. Patients (N=130) who had undergone curative therapy were randomised to undergo either conventional (Con) or FDG-PET procedures during follow-up. The two groups were matched at baseline. Recurrence was confirmed histologically. 'Intention-to-treat' analysis revealed a recurrence in 46 patients (25 in the FDG-PET group, and 21 in the Con group; P=0.50), whereas per protocol analysis revealed a recurrence in 44 out of 125 patients (23 and 21, respectively; P=0.60). In another three cases, PET revealed unexpected tumours (one gastric GIST, two primary pulmonary cancers). Three false-positive cases of FDG-PET led to no beneficial procedures (two laparoscopies and one liver MRI that were normal). We failed to identify peritoneal carcinomatosis in two of the patients undergoing FDG-PET. The overall time in detecting a recurrence from the baseline was not significantly different in the two groups. However, recurrences were detected after a shorter time (12.1 vs 15.4 months; P=0.01) in the PET group, in which recurrences were also more frequently (10 vs two patients) cured by surgery (R0). Regular FDG-PET monitoring in the follow up of colorectal cancer patients may permit the earlier detection of recurrence, and influence therapy strategies.     

尿液中循环肿瘤DNA水平预测非肌层浸润性膀胱癌术后复发及进展的临床价值

目的:探讨尿液中循环肿瘤DNA（circulating tumour DNA,ctDNA）水平在非肌层浸润性膀胱癌（non-muscle-invasive bladder cancer,NMIBC）术后预测复发及进展中的临床价值。方法:选取2017年06月至2019年06月在我院收治的膀胱癌患者96例,均接受经尿道膀胱肿瘤电切术（transurethral resection of bladder tumor,TURBT）,且术后病检均证实为非肌层浸润性膀胱尿路上皮癌。根据术后病检结果分为两组:A组:高级别NMIBC患者46例,B组:低级别NMIBC患者50例。术后每个月测定患者尿液中ctDNA的水平,每3个月复查泌尿系彩超、膀胱镜及尿脱落细胞学检查,每6个月复查膀胱CT;所有患者术后均进行随访,随访期18个月,影像学或膀胱镜检查证实肿瘤临床复发或进展为肌层浸润性膀胱癌（muscle-invasive bladder cancer,MIBC）时即停止随访。结果:在随访期内共有62例患者通过膀胱镜检查或影像学手段证实肿瘤出现了复发或进展,其中A组有36例,B组有26例,两组间差异具有统计学意义（P＜0.05）;在肿瘤复发或进展的62例患者中,A组尿液ctDNA阳性患者27例,B组尿液ctDNA阳性患者21例,差异无统计学意义（P＞0.05）;两组共有63例患者在影像学及膀胱镜检查有异常之前首先从尿液中检测到了ctDNA,其中48例患者在之后的随诊复查中证实肿瘤出现了复发或进展;肿瘤进展组患者尿液中ctDNA水平显著高于复发组,差异具有统计学意义（P＜0.05）。结论:通过液态活检技术动态检测NMIBC术后患者尿液中ctDNA的水平,能更早地发现肿瘤的复发及进展,具有较高的特异性,而且与肿瘤进展存在一定的相关性,可能成为NMIBC术后辅助监测肿瘤早期复发或进展的新手段。     

Efficacy of intra-arterial chemotherapy on life prolongation in patients with hepatic metastasis from colorectal cancer

The efficacy of intra-arterial chemotherapy for life prolongation was investigated in patients with hepatic metastasis from colorectal cancer who visited our hospital from Jan. 1989-Mar. 1999, but without any other remote metastasis when the presence of their hepatic metastasis was detected. The subjects were assigned to 4 groups; group A (n = 8) was only treated by hepatectomy, group B (n = 27) by intra-arterial chemotherapy combined with hepatectomy, group C (n = 42) with intra-arterial chemotherapy alone, and group D (n = 23) by systemic chemotherapy through intra-venous or oral administration. The survival rates of these groups were determined, and the recurrence risk after hepatectomy was compared between group A and B. Further, the survival rate of the patients treated by intra-arterial chemotherapy was compared between the cases of PD and not-PD (including CR, PR, and NC). The median survival in cases of H1 and H2 was 405 days for group A, 1,018 days for group B and 245 days for group C, showing that group B had a significantly more favorable prognosis than either group A or group C. There were also significant differences in the median survival of H3 cases between group C (422 days) and group D (113 days). One-year cumulative recurrence risks in the residual livers of group A and group B were 79% and 28%, respectively. Thus, significant differences in the recurrence risk were found in the two groups. Meanwhile, the median survival of PD and non-PD cases was 240 and 588 days, respectively. These results suggested that local control by intra-arterial chemotherapy is useful for life prolongation.     

Salvage treatment for local or local-regional recurrence after initial breast conservation treatment with radiation for ductal carcinoma in situ

The present study evaluated the outcome of salvage treatment for women with local or local-regional recurrence after initial breast conservation treatment with radiation for mammographically detected ductal carcinoma in situ (DCIS; intraductal carcinoma) of the breast. The study cohort consisted of 90 women with local only first failure (n=85) or local-regional only first failure (n=5). The histology at the time of recurrence was invasive carcinoma for 53 patients (59%), non-invasive carcinoma for 34 patients (38%), angiosarcoma for one patient (1%), and unknown for two patients (2%). The median follow-up after salvage treatment was 5.5 years (mean=5.8 years; range=0.2-14.2 years). The 10-year rates of overall survival, cause-specific survival, and freedom from distant metastases after salvage treatment were 83%, 95%, and 91%, respectively. Adverse prognostic factors for the development of subsequent distant metastases after salvage treatment were invasive histology of the local recurrence and pathologically positive axillary lymph nodes. These results demonstrate that local and local-regional recurrences can be salvaged with high rates of survival and freedom from distant metastases. Close follow-up after initial breast conservation treatment with radiation is warranted for the early detection of potentially salvageable local and local-regional recurrences.     

The role of regional hyperthermic cytostatic perfusion in the treatment of extremity melanoma

To evaluate the effectiveness of regional hyperthermic cytostatic perfusion in patients with malignant melanomas of the extremities, 107 patients were included in a prospective randomized study. In a control group (A, n = 54) the tumors were widely excised, and the regional lymph nodes were dissected. The patients in the perfusion group (B, n = 53) received additional hyperthermic (42 degrees C) perfusion with melphalan. The disease-free survival time was chosen as the criterion for success. An intermediate evaluation (average follow-up observation period of 550 days) revealed a highly significant difference between the groups (P = 0.0001): 21 recurrences in the control group versus four recurrences in the perfusion group. In a second analysis 3 1/2 years after premature discontinuation, 26 recurrences were diagnosed in Group A, whereas only six recurrences were noted in Group B (P = 0.0001). A retrospective analysis of the entire test group revealed the following figures. In Group A seven recurrences in Stage I were diagnosed, seven in Stage II, and 12 in Stage III. In Group B one was observed in Stage I, one in Stage II, and four in Stage III. The level of significance was calculated to be P = 0.05 in Stage I, P = 0.05 in Stage II, and P = 0.01 in Stage III. The results of the study show that additional perfusion in the treatment of extremity melanomas is superior to conventional methods.     

肝癌患者术后肝动脉化疗栓塞联合胸腺肽治疗预防复发的随机对照研究

目的 随机对照观察肝癌患者术后肝动脉化疗栓塞(TACE)联合胸腺肽α1(Tα1)治疗对预防肝细胞癌复发的影响。方法 57例肝细胞癌患若随机分为3组：手术＋TACE Tα1组(A组)18例,手术＋FACE组(B组)23例和手术切除组(C组)16例。观察患者术后肿瘤复发率、复发时间和生存期。结果 A、B、C组1年复发率分别为83．3％、87．0％和87．5％(P=0．926),中位复发时间分别为7．0个月、5．0个月和4,0个月(P=0,039),中位生存期分别为10．0个月、7．0个月和8,0个月(P=0．002)。结论 术后TAC：E rr0．治疗不能降低肝细胞癌患者术后复发率,但可延缓复发时间,提高生存期。     

Surveillance for recurrent head and neck cancer using positron emission tomography.

PURPOSE: Earlier detection of head and neck cancer recurrence may improve survival. We evaluated the ability of [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) to detect recurrence in a prospective trial using sequential PET scans. PATIENTS AND METHODS: Serial posttherapy FDG-PET was prospectively performed in 44 patients with stage III or IV head and neck cancer. PET was performed twice during the first posttreatment year (at 2 and 10 months after therapy) and thereafter as needed. After therapy, patients were grouped, based on tissue biopsies, into those who achieved a complete response (CR) and those who had residual disease (RD). Patients who achieved a CR were further grouped into those without evidence of disease and those who had recurrence by 1 year after completion of therapy. Disease status as determined by physical examination (PE), PET, and correlative imaging was compared. RESULTS: Eight patients were lost to follow-up and six had RD after therapy. Of the remaining 30 patients with a CR, 16 had recurrence in the first year after therapy. Five of these 16 patients had recurrence detected by PET only, four by PET and correlative imaging only, five by PE and PET only, and two by PE, correlative imaging, and PET. Only PET detected all recurrences in the first year. PET performed better than correlative imaging (P =.013) or PE (P =.002) in the detection of recurrence. CONCLUSION: PET can detect head and neck tumor recurrence when it may be undetectable by other clinical methods. FDG-PET permits highly accurate detection of head and neck cancer recurrence in the posttherapy period.     

Ⅱ、Ⅲ期直肠癌新辅助放化疗与手术间隔时间对术后病理及临床疗效的影响

目的:探讨局部晚期直肠癌新辅助放化疗结束与手术的间隔时间对病理及临床疗效的影响。方法:回顾性分析2010年1月至2013年7月间接受新辅助放化疗随后行根治性手术的78例初治局部晚期直肠癌患者的临床资料。根据新辅助治疗结束至手术的间隔时间中位数分为两组,A组为新辅助放化疗结束后﹤7周手术治疗38例;B组为≥7周手术治疗40例。全部患者采用三维适形调强放疗,2Gy/1次, 5次/1周,总50Gy,同步行氟尿嘧啶为基础的化疗,比较两组患者肿瘤病理退缩分级（TGR）、降期率、手术并发症发生率、局部复发率、远处转移率和生存率。结果:TRG1、TRG2、TRG3、TRG4（PCR）A组分别为 9例、7例、10例、6例,B组分别为9例、9例、12例、8例（P=0.614）;T分期降期率A组63.2%,B组52.5%（P=0.368）,N分期降期率A组39.5%,B组55%（P=0.039）;手术并发症发生率A组18.4%,B组20%（P=0.550）;3年复发率A组7.9%,B组10%（P=0.745);远处转移率A组13.2%,B组10%（P=0.663）;3年生存率A组70.8%,B组84%（P=0.453）。结论:新辅助放化疗结束≥7周行手术,可以获得较高的淋巴结降期率,不增加手术难度和并发症发生率。     

Value of intensive follow-up of patients after curative surgery for gastric carcinoma

OBJECTIVE: Most clinicians perform surveillance after gastrectomy for gastric cancer. There is no consensus on the regimen, follow-up interval and choice of investigations. This study aims to review the long-term results of patients followed-up in our institution after gastrectomy for gastric cancer. METHODS: Patients with gastric carcinoma who had undergone gastrectomy between 1995 and 1998 were reviewed. The patients were assigned to either intensive or regular regimen based on the follow-up they had undergone. Intensive regimen included routine physical examination, serum tumor markers, and the use of computed tomography (CT) scan of more than once per year in the follow-up. RESULTS: A total of 102 patients were reviewed. Forty-nine patients received intensive and 53 patients received regular follow-up. Recurrences were detected earlier in the intensive group (11.5 vs. 19.2 months, P = 0.02). There was no difference in the length of survival in the two groups. Most recurrences (60%) were detected by CT scan. CONCLUSIONS: Intensive follow-up after gastrectomy resulted in the earlier detection of recurrences. However, there was no survival benefit from this regimen. A regimen based on symptoms and physical examination is adequate for most patients. CT was the most useful investigation for detection of recurrences.     

The Role of Surveillance Magnetic Resonance Imaging (MRI) Scanning in Detecting Recurrent Brain Tumors in Asymptomatic Children

BACKGROUND: There is controversy regarding the utility of routine surveillance scanning for asymptomatic children with brain tumors. Although the role of CT or magnetic resonance imaging (MRI) scanning in this setting has been examined in several studies, none have focused on children followed exclusively by MRI. The purpose of this study was to determine how often recurrent brain tumors are detected by routine MRI surveillance in asymptomatic children. METHODS: The medical records of all children with brain tumors treated at Children's Hospital at Strong from 1990-1999 were reviewed. Recurrence was defined as an increase in size of the tumor on MRI scan. Astrocytomas and gangliogliomas were classified as low-grade tumors; high-grade astrocytomas, medulloblastomas, and ependymomas were classified as high-grade tumors. RESULTS: Of the 112 evaluable children with brain tumors during this time period, 46 (41%) suffered an MRI-documented recurrence. Of these 46 patients, 13 (28%) had low-grade tumors and 33 (72%) had high-grade tumors. Twenty-seven of the 46 recurrences (59%) occurred in asymptomatic children. Ten of the 13 children (77%) with recurrent low-grade tumors were asymptomatic compared to 17 of 33 children (52%) with recurrent high-grade tumors (p = 0.18). The median survival from time of recurrence for the symptomatic children was seven months, while the median survival from time of recurrence for the asymptomatic children has not yet been reached (p = 0.025). When the analysis was confined to children with high-grade tumors, there was no difference in median survival from the time of recurrence for symptomatic versus asymptomatic children (5 mo. versus 7 mo.) (p = 0.25). The frequency of detection of recurrences by surveillance scanning in asymptomatic children was 4.2% (one recurrence detected per 24 surveillence MRI scans). CONCLUSION: The majority of recurrent brain tumors are detected by MRI surveillence in asymptomatic children. However, asymptomatic recurrences were detected in only a small proportion of surveillance scans and had no impact on survival in children with high-grade tumors.     

Patients’ and physicians’ roles in detecting recurrent Hodgkin lymphoma following complete remission

BackgroundOptimal post-treatment surveillance for patients with Hodgkin lymphoma in first complete remission (CR) is unknown. Guidelines are based on consensus rather than high-quality evidence. It is unknown if routine screening leads to earlier relapse detection or translates into better outcomes.Patients and methodsWe identified 258 patients with relapse after CR and determined whether the recurrence was detected as a result of patient-detected symptoms (PT group) or through exams or tests ordered by the physician in the absence of symptoms (MD group).ResultsOf 258 recurrences, 182 (71%) were in the PT group. The median time to diagnosis of recurrence was similar in both groups (PT group = 1.65 years; MD group = 1.95 years; P = 0.69). Neither the postrelapse progression-free (PFS, P = 0.26) nor overall survival (OS, P = 0.40) differed significantly between the groups.ConclusionPatients are much more likely to detect recurrence than their physicians employing routine follow-up testing. There is no difference in PFS or OS between patients whose recurrence is self-diagnosed versus those whose recurrence is diagnosed by physician through routine screening. We found no benefit for detection of HL recurrence in asymptomatic patients and thus cannot support the routine use of costly, anxiety-provoking or potentially harmful tests in the absence of symptoms.     

Clinical importance of late recurrence in soft-tissue sarcomas

BACKGROUND AND OBJECTIVES: Soft-tissue sarcomas (STS) represent a diverse histologic group of malignancies at risk for local and distant failure. We studied the impact of late (5 or more years) vs. early recurrence (less than 5 years) on subsequent outcome. METHODS: Four hundred sixty-eight patients with STS treated between 1962 and 1992 were evaluated for late (n = 39; 8%) or early (n = 253; 54%) recurrence. Clinical and pathologic factors were reviewed. Survival data were analyzed by the Kaplan-Meier method and the log-rank test. RESULTS: Of the 39 patients with a late recurrence (median follow-up 156 months), 18 patients had local recurrence, 7 patients developed distant recurrence, and 14 patients had local and distant recurrence. Thirty patients with late local and/or distant recurrence underwent complete or wide excision (n = 16), amputation (n = 4), or local resection (n = 10). The overall 5-year survival rate following late recurrence was 61%. The 5-year overall survival rate was statistically better for patients with a late local recurrence alone than for patients with distant failure, 94% vs. 36%, respectively (P = 0.003). Neither the site of the primary STS, age, primary margin status, nor histology had any effect on subsequent local or distant failure and subsequent survival. CONCLUSIONS: These data suggest that an aggressive approach is appropriate in patients who present with late recurrence (more than 5 years) following treatment of the primary STS. Impressive survival rates can be achieved in the treatment of local recurrences.     

TACE与γ刀治疗原发性肝癌时序探讨

目的：探讨经肝动脉插管化疗栓塞术（ TACE）和γ射线立体定向放射（γ刀）在不同时序上介入对原发性肝癌的疗效。方法：将53例原发性肝癌患者分为A、B两组,A组先行TACE后行γ刀治疗,B组先行γ刀后行TACE治疗,对照分析两组在疗效、生存期、复发时间、不良反应等方面的差异。结果：两组有效率分别为77.4％和77.3％,随访6、12、18个月,生存率分别为96.8％、80.6％、77.4％和63.6％、45.5％、18.2％。复发率分别为0％、16.1％、35.5％和18.2％、40.9％、77.3％。不良反应相似。结论：两组在有效率方面无差异,但在生存期和复发时间方面A组明显优于B组,而不良反应相似,表明不同方法在不同时序上介入对原发性肝癌治疗结果有直接影响。     

Safety and efficacy results of a randomized trial comparing adjuvant toremifene and tamoxifen in postmenopausal patients with node-positive breast cancer. Finnish Breast Cancer Group.

PURPOSE: In this multicenter trial, toremifene 40 mg/d was compared with tamoxifen 20 mg/d, both given orally for 3 years to postmenopausal, axillary node-positive women after breast surgery. PATIENTS AND METHODS: The first 899 patients (toremifene, n = 459; tamoxifen, n = 440) of the total of 1,480 patients accrued to the trial were included in this scheduled safety analysis. The mean follow-up time was 3.4 years. RESULTS: The two treatment groups were well balanced with respect to patient and disease characteristics. The subjective side-effect profile was similar in both treatment groups. Slightly more vascular complications (deep vein thromboses, cerebrovascular events, and pulmonary embolisms) were seen among tamoxifen-treated patients (5.9%) as compared with toremifene-treated patients (3.5%) (P: =.11), whereas bone fractures (P: =.09) and vaginal leukorrhea (P: =.05) were more common in the toremifene group. The number of subsequent second cancers was similar. The breast cancer recurrence rate was 23.1% (n = 106) in the toremifene group and 26.1% (n = 115) in the tamoxifen group (P: =.31). When only patients with estrogen receptor (ER)-positive cancer were considered (n = 556), the risk for breast cancer recurrence was nonsignificantly lower among the toremifene-treated women, with a hazards ratio of 0.74 (90% confidence interval, 0.52 to 1.04; P: =.14). The mean time to breast cancer recurrence and overall survival were similar in both groups. CONCLUSION: The side-effect profile of toremifene resembles that of tamoxifen. The efficacy of toremifene seems to be no less than that of tamoxifen. The trend for fewer breast cancer recurrences in the ER-positive subgroup is encouraging, but a longer follow-up is needed to confirm this.     

Association of matrilysin expression with recurrence and poor prognosis in human esophageal squamous cell carcinoma.

Matrix metalloproteinase-7 (matrilysin) has been implicated in tumor invasion and metastasis as well as tumor initiation and growth. In this study, we analyzed an association between immunohistochemically detected matrilysin expression at the invasive front in esophageal squamous cell carcinomas and clinicopathological characteristics and determined whether matrilysin predicts recurrence and/or survival Matrilysin expression at the invasive front was detected in 49% of 100 carcinoma tissues and was associated with the depth of invasion (P < 0.0001), advanced tumor stage (P = 0.0159), recurrences (P = 0.0002), and recurrences within the first postoperative year (P = 0.002). Patients with matrilysin-positive carcinoma had a significantly shorter disease-free and overall survival time than did those with a matrilysin-negative one (P < 0.0001). Matrilysin remained a significant predictive value for disease-free and overall survival in multivariate analysis, including conventional clinicopathological factors (P = 0.0007 and 0.0004, respectively). Our results suggest that matrilysin may play a key role in the progression of esophageal carcinoma and that its detection may be useful for the prediction of recurrence and poor prognosis and, possibly, for selecting patients for anti-matrix metalloproteinase therapy.     

Surveillance improves survival of colorectal cancer in patients with hereditary nonpolyposis colorectal cancer

Some patients with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome develop carcinoma despite surveillance. The aim of this study was to determine whether survival was greater in colorectal cancer (CRC) cases detected by surveillance than in patients who had disease diagnosed on the basis of symptoms. All 150 CRC cases detected in 57 HNPCC families over the last 15 years were divided into two groups depending on whether they had been included in the surveillance program (n = 35) or not (n = 115). The stage distribution of the tumors in the group that underwent surveillance (Dukes' A, 50%; B, 35%; C, 15%; D, 0%) was significantly more favorable (P < .001) than in the group without surveillance (Dukes' A, 17%; B, 50%; C, 16%; D, 17%). CRC-specific 10-year survival was 93% in the surveillance group, significantly better than the 68% in the nonsurveillance group (P < .02). The overall survival did not differ significantly between the two groups despite a tendency in favor of the surveillance group. Colonoscopic surveillance enables early detection of CRC in HNPCC and reduces CRC mortality.     

Long-term results of local recurrence after breast conservation treatment for invasive breast cancer

PURPOSE: The outcome for women with a local failure after breast conservation treatment is not well described in the literature. Because local recurrence is a potentially salvageable event, this study was performed to evaluate the outcome of patients with local recurrence after breast conservation surgery and definitive radiation treatment. METHODS AND MATERIALS: The study population consisted of 112 patients with ipsilateral breast tumor recurrence. There were 100 isolated local recurrences and 12 local-plus-regional recurrences. There were 93 invasive local recurrences and 19 DCIS (ductal carcinoma in situ) local recurrences. Local recurrences were detected by physical examination alone in 42 patients, mammography alone in 47 patients, and both modalities in 23 patients. All patients were initially treated with breast conservation treatment with or without systemic therapy and subsequently treated at the time of local recurrence with salvage mastectomy with or without systemic therapy. The mean and median follow-up times after local recurrence were 49 and 44 months, respectively. RESULTS: For the entire group of 112 patients, the overall survival at 10 years after local recurrence was 69%, the cause-specific survival was 71%, and the freedom from distant metastases was 47%. For the 93 patients with an invasive local recurrence, the overall survival at 10 years was 64%, cause-specific survival was 67%, and freedom from distant metastases was 44%. For the 93 patients with an invasive local recurrence, interval from diagnosis to local recurrence (< or =2 years vs. 2.1-5 years vs. >5 years) predicted for overall survival at 5 years (65% vs. 84% vs. 89%; p = 0.03). Method of detection of local recurrence (physical examination vs. mammography vs. both methods) also predicted for 5-year overall survival (73% vs. 91% vs. 93%, respectively; p = 0.04). On multivariable analysis, interval from diagnosis to local recurrence was an independent predictor of overall survival (p = 0.03). Method of detection of local recurrence (physical examination vs. mammography vs. both methods) was borderline in predicting for 5-year cause-specific survival (73% vs. 91% vs. 93%, respectively; p = 0.06). Similarly, interval from diagnosis to local recurrence (< or =2 years vs. 2.1-5 years vs. >5 years) was a borderline predictor of 5-year cause-specific survival (65% vs. 84% vs. 89%; p = 0.08). No factors that predicted for freedom from distant metastases were identified. There were three second locoregional failures on the chest wall. Two of the 19 patients with a DCIS local recurrence have died of metastatic breast cancer. Death was probably not related to their local recurrence, but rather a result of persistent risk from an invasive primary cancer. CONCLUSIONS: This analysis provides long-term data after salvage treatment for patients who experience local recurrence after breast conservation treatment. The variables of method of detection and interval from diagnosis to local recurrence are identified as having prognostic significance for overall and cause-specific survival. In view of the potential for long-term survival, aggressive attempt at salvage treatment is warranted for the patient with local recurrence after breast conservation treatment. Second local recurrence after salvage mastectomy is an uncommon event. Although DCIS local recurrences may not in themselves cause an increase in the risk of mortality, the risk from the primary invasive cancer persists.     

Postoperative chemotherapy vs chemoradiotherapy for thoracic esophageal cancer: a prospective randomized clinical trial.

BACKGROUND: Neither postoperative radiotherapy nor chemotherapy alone provided a survival benefit after curative esophagectomy for esophageal squamous carcinoma. MATERIAL AND METHODS: Of 103 consecutive patients who underwent potentially curative esophagectomy for esophageal squamous carcinoma, 45 patients with advanced cancers without preoperative adjuvant treatments were prospectively randomized to two groups; postoperative chemotherapy alone (Group A, n=23) and postoperative radio/chemotherapy (Group B, n=22). In Group A, cisplatin (CDDP) (50 mg/m(2)) was given by intravenous infusion on days 1 and 15, and 5-fluorouracil (5-FU) (300 mg/m(2)) was given daily by continuous intravenous infusion for 5 weeks. In Group B, in addition to the same chemotherapeutic regimen of Group A, 50 Gy of radiotherapy was given to the mediastinum over 5 weeks. The immunohistochemical staining of tumoral p53 and microvessel density was undertaken to correlate to the radio/chemosensitivity. RESULTS: There were no significant differences in the clinicopathologic characteristics between the two groups. The median dose of 5-FU and CDDP administered were not significantly different between the two groups. The mean (SD) dose of radiotherapy in Group B was 42+10 Gy. The 1-, 3- and 5-year survival rates in Group A were 100, 63 and 38% and those in Group B were 80, 58 and 50%, respectively (P=0.97). In each group, four patients succumbed to locoregional recurrences.Tumoral p53 was immunohistochemically negative in 43% in Group A and 77% in Group B (P=0.03), indicating that many patients in Group B might be potentially sensitive to radiochemotherapy. The 3- and 5-year survival rates (75 and 64%) of patients with p53 negative expression (n=18) were significantly (P=0.03) better than those with p53 positive expression (n=27, 44 and 26%). The long-term survival was better for patients with p53 negative tumours than those with p53 positive tumours in Group B (P=0.06 by long-rank test, P<0.05 by Generalized-Wilcoxon test). However, the long-term survival was not different between the patients who had p53 negative and positive tumours in Group A (P=0.19). These data suggest that there were no survival advantage for patients receiving radiotherapy in Group B, instead p53 negative tumours appeared to have a favorable prognosis. CONCLUSION: Postoperative radiotherapy administered concurrently with chemotherapy does not provide a survival benefit compared with chemotherapy alone. Tumoral p53 expression has a predictive value for survival in patients treated with postoperative radio/chemotherapy.     

Comparison of clinical and molecular surveillance in patients with advanced nasopharyngeal carcinoma after primary therapy: the potential role of quantitative analysis of circulating Epstein-Barr virus DNA

BACKGROUND: The importance of detecting recurrence at an early stage in patients with malignant disease is well recognized. Circulating Epstein-Barr virus (EBV) DNA can be detected in patients with nasopharyngeal carcinoma (NPC). The objective of the current study was to assess the effectiveness of plasma EBV DNA monitoring in the early detection of NPC recurrence compared with conventional methods. METHODS: Patients with NPC in two prospective clinical trials who had locoregional recurrences or distant metastases were recruited into the study. Clinical data on these patients were scrutinized for evidence of recurrence. EBV DNA copy numbers in the prospectively collected plasma samples were assayed retrospectively with real-time quantitative polymerase chain reaction analysis. RESULTS: At the time of clinical recurrence, 65% of 26 patients with locoregional recurrences and all but 1 of 28 patients with distant failure had circulating EBV DNA. The difference between the time from completion of treatment to positivity for circulating EBV DNA and the time from completion of treatment to the first observed clinical abnormality was not statistically significant for patients with local recurrence (P=0.84). However, the time to the first detection of circulating EBV DNA was significantly shorter among patients with distant metastases (P<0.0001). The Kaplan-Meier estimated median time to the emergence of plasma EBV DNA was 190 days, with a 95% confidence interval (CI) of 95-300 days, and the median time to the first observed clinical abnormality was 295 days (95% CI, 276-361 days). CONCLUSIONS: Monitoring plasma EBV DNA levels surpassed traditional methods for the early detection of distant failure in patients with NPC. The role of this technique should be evaluated in prospective studies that incorporate complementary advanced imaging technology.