The thymidylate synthase tandem repeat promoter polymorphism: A predictor for tumor-related survival in neoadjuvant treated locally advanced gastric cancer

We evaluated DNA polymorphisms in the thymidylate synthase (TS) and 5,10-methylene-tetrahydrofolate reductase (MTHFR) genes for an association with response and survival in locally advanced gastric cancer treated with 5-FU based preoperative chemotherapy (CTx). DNA of 238 patients (CTx-group: total n = 135, completely resected (R0) n = 102; without CTx: R0 n = 103) was isolated from blood or from nontumorous tissues. In the CTx-group, genotyping of the tandem repeat and the G/C polymorphism in the triple repeat in the promoter region of the TS gene and of the C677T polymorphism of the MTHFR gene was performed. None of the TS or MTHFR genotypes were associated with histopathological response and only the TS tandem repeat polymorphism was significantly related to survival (all patients n = 135, p = 0.002; R0 resected patients n = 102, p = 0.007; log-rank test). Multivariate analysis revealed ypN (p < 0.001) and the TS tandem repeat polymorphism as independent prognostic factors in the CTx-R0-group (p = 0.003). Analyzing the prognostic significance of the TS polymorphisms in the R0-group without CTx, TS genotypes were not significantly associated with survival. Comparing survival between R0 patients with and without CTx in the respective TS genotype groups of the tandem repeat polymorphism, a significant survival benefit for the patients with CTx was found for the 2rpt/2rpt (n = 49; p = 0.002) and 2rpt/3rpt genotypes (n = 99; p = 0.004), but not for the 3rpt/3rpt genotype (n = 57; p = 0.93). Patients' survival after CTx was associated with the TS tandem repeat polymorphism. CTx did not improve survival of patients with the 3rpt/3rpt genotype. Thus, a different therapy might be more appropriate for these patients.     

Outcome of gastric cancer patients after successful gastrectomy: influence of the type of recurrence and histology on survival

BACKGROUND: The effect of the location of disease recurrence after curative (R0) gastrectomy on patient survival has not been elucidated. The authors hypothesized that the location of recurrence would have a significant influence on survival. METHODS: Medical records of all patients who received treatment for gastric cancer at The University of Texas M. D. Anderson Cancer Center between 1985 and 1998 were reviewed. Patients who underwent R0 resection for gastric cancer and subsequently developed localized (anastomotic) recurrence (LR), lymph node (regional) recurrence (NR), or distant metastases (DM) were analyzed for overall survival (OS). All study factors were entered into a Cox proportional hazards model to provide multivariate hazard ratios. The model was adjusted for the effects of primary site of recurrence, histologic grade, patient age, and location of the primary tumor. RESULTS: This retrospective analysis included 227 consecutive patients. The median survival of patients who developed NR (11 months) was similar to that of patients who developed LR (10 months), but both groups had significantly longer median survival compared with patients who developed DM (7 months; log-rank P = .03). Patients who had well differentiated or moderately differentiated tumors had a longer OS (11 months) than patients who had poorly differentiated tumors (8 months; log-rank P = .02). In this cohort, location of the primary cancer and age at recurrence had no significant impact on OS. CONCLUSIONS: The data from this study suggested that, among patients who undergo R0 gastrectomy for gastric cancer, LR and NR versus DM should be considered a valid stratification factor for randomized trials based on significant differences in survival. Determining whether this stratification should apply to histologic differentiation will require further investigation in a larger multicenter cohort.     

218例食管癌根治术后复发再治疗的疗效分析

目的 分析食管癌根治术后复发挽救治疗的疗效,为综合治疗提供依据。 方法 回顾分析2004—2014年间食管癌R₀术后复发转移行挽救治疗的218患者资料。采用Kaplan-Meier法计算生存率并Logrank法检验和单因素预后分析,Cox模型多因素预后分析。 结果 全组患者复发后中位随访时间53个月。复发后1、3年OS率分别为57.2%、24.4%。163例局部区域复发患者复发后放化疗(40例),单纯放疗(106例),支持治疗(13例)的1、3年OS率分别为70%、42%,55%、24%,23%、8%(放化疗比单纯放疗 P=0.045,单纯放疗比支持治疗 P=0.004,单纯化疗无 1年生存)。单因素分析显示术后病理N分期、TNM分期、复发后治疗方式影响预后(P均=0.001),多因素分析中只有复发后治疗方式是影响生存的独立预后因素(P=0.013)。 结论 食管癌根治术后复发转移后采用放化疗或放疗挽救治疗有明显生存获益,特别是局部区域复发患者。     

Complete response to neoadjuvant chemoradiotherapy in esophageal carcinoma is associated with significantly improved survival.

PURPOSE: Attempts to improve survival of patients with esophageal cancer have been made using induction chemoradiotherapy (CRT) followed by surgery. A large single-center experience was reviewed to determine which treatment-related variables could predict survival and recurrence. PATIENTS AND METHODS: All patients undergoing esophagectomy between January 1994 and December 2002 were reviewed. Univariate and multivariate analyses were performed using log-rank and Cox proportional hazards models, and survival curves were estimated using the Kaplan-Meier method. RESULTS: Of 171 patients with invasive cancer, 131 (77%) underwent preoperative CRT. The average age was 60 years, and most patients were male (85%). Operations performed included Ivor-Lewis (60%), transhiatal (8%), three-hole (23%), or left thoracoabdominal (8%) esophagectomy. Perioperative mortality rate was 5%. Median overall survival (OS) of the entire group was 33 months, and the 5-year OS rate was 26%. Induction CRT was associated with a 33% 5-year survival rate compared with 11% for surgery alone (P = .43). Patients downstaged to pathologic stage 0 or I had an improved OS and disease-free survival (DFS) compared with those patients who were not downstaged (P = .022). Additionally, the ability to perform an R0 resection was a significant factor for OS and DFS (n = 130; P < .0001 and P <.0002, respectively). CONCLUSION: Response to CRT and the ability to perform an R0 resection are associated with significantly improved survival in patients with esophageal carcinoma.     

Expression of TRAIL and TRAIL receptors in colon carcinoma: TRAIL-R1 is an independent prognostic parameter.

PURPOSE: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in cancer cells and may be involved in protection from metastases. TRAIL receptor (TRAIL-R) 1 and TRAIL-R2, but not TRAIL-R3 and TRAIL-R4, mediate apoptosis. We examined the expression of TRAIL and its receptors in normal and neoplastic colon epithelium, and studied its correlation with prognosis in colon cancer. EXPERIMENTAL DESIGN: Immunohistochemistry was performed on normal colon mucosa (n = 10), colon adenomas (n = 20), and R0-resected Unio Internationale Contra Cancrum stage II/III colon carcinomas (n = 129). Disease-free survival was examined by Kaplan-Meier estimates and the log-rank test. Prognostic factors were determined by multivariate Cox-analysis. RESULTS: In normal colon mucosa, TRAIL and TRAIL-R2 were expressed mostly in the surface epithelium, whereas TRAIL-R1 and TRAIL-R4 were detected all along the crypt axis. In adenomas, this expression pattern was mostly retained, although some adenomas also neoexpressed TRAIL-R3. In carcinomas, the expression of TRAIL and TRAIL receptors was much more variable. TRAIL, TRAIL-R2, TRAIL-R3, and TRAIL-R4 expression did not correlate statistically with disease-free survival (multivariate analysis: P = 0.54, P = 0.67, P = 0.45, and P = 0.69, respectively), but TRAIL-R1 expression was significantly associated with disease-free survival in colon cancer (multivariate analysis: P = 0.003). CONCLUSIONS: TRAIL-R1 is an independent prognostic factor in R0-resected Unio Internationale Contra Cancrum stage II/III colon cancer.     

Long-Term Prognosis after Surgery for Locally Recurrent Rectal Cancer: A Retrospective Study

Objective: Resection is usually recommended for locally recurrent rectal cancer (LRRC) for which R0 resection is possible, but its suitability varies by individual patient risk. Here, we report outcomes of resected LRRC in our hospital. Methods: We retrospectively evaluated short- and long-term results of 33 patients who underwent resections for LRRC from January 2003 to December 2019. Results: At the initial surgeries for these 33 patients, their disease stages at that time were Stage I: n=2, Stage II: n=12, Stage III: n=11, Stage IV: n=6, and unknown: n=2. Patients with Stage IV disease at their initial surgeries underwent radical one-step or two-step procedures. Metastasis to other organs was observed in 5 patients at the their initial LRRC diagnoses. At the LRRC surgeries, 7 patients received palliative surgeries; 26 received intent-to-treat resections, of which 17 were R0 resections. All-grade postoperative complications were observed in 11 patients, including 1 surgery-related death. Five-year overall survival rates were all cases: 38.4%; R0 group: 52.3%, R1 or R2 group: 19.4%, and palliative surgery group: 0%. The R0 group thus had significantly better prognosis than other patients (P = 0.0012). Eleven patients in the R0 group (64.7%) suffered re-recurrences but some patients achieved long-term survival through chemotherapy, radiation therapy, and surgery for metastasis to other organs, even after re-recurrence. Conclusion: Long-term prognosis after surgery for LRRC was significantly better for patients with R0 margins. Multimodal treatments may greatly improve survival for patients who suffer re-recurrences after local recurrence resections.     

食管癌疗后锁骨上淋巴结转移挽救性放疗的临床研究

目的 探讨食管癌首次治疗后锁骨上淋巴结转移挽救性放疗的价值。方法 收集2006—2012年符合入组条件的117例患者,应用3DRT方式,1.8~2.0 Gy/次,5 次/周。Kaplan-Meier法计算生存率并Logrank法检验,Cox模型多因素分析。结果 随访率100%。锁骨上淋巴结转移后的1、3年OS率分别为38.5%、14.1%。挽救放疗或放化疗(100例)与未挽救治疗(17例)的1、3年OS率分别为42%、17%与18%、0%(P=0.008);放化疗(32例)的1、3年OS率分别为59%、36%,高于单纯放疗(68例,34%、11%)和未挽救者(17例,18%、0%)(P=0.002);未合并内脏转移(80例)和合并内脏转移(37例)患者1、3年OS率分别为44%、22%和27%、0%(P=0.002);锁骨上挽救放疗剂量<60 Gy (25例)和≥60 Gy (75例)的1、3年OS率分别为25%、8%%和75%、24%(P=0.000)。Cox模型多因素生存分析显示锁骨上挽救放疗剂量≥60 Gy、合并纵隔失败、合并内脏转移、挽救方式为影响锁骨上淋巴结转移后生存因素(P=0.001、0.015、0.009、0.025)。结论 食管癌锁骨上淋巴结转移挽救性放疗可使患者生存获益,单纯锁骨上淋巴结转移患者建议积极行挽救性放疗或放化疗,挽救性放疗剂量≥60 Gy者可延长生存。     

Cyclin D1, p16 and retinoblastoma gene product expression as a predictor for prognosis in non-small cell lung cancer at stages I and II.

The association of the immunohistochemical expressions of cyclin D1, p16 and the retinoblastoma gene product (pRB) with the prognoses of 106 patients with non-small cell lung cancer (NSCLC) at stages I and II after a complete resection was investigated. We used antibodies recognizing nuclear and cytoplasmic cyclin D1, p16 and pRB. In 106 tumors, the positive rates of cyclin D1, p16 and pRB were 46, 54 and 48%, respectively. Cyclin D1-positive (cyclin D1(+)) patients had significantly poorer survival prognoses than cyclin D1-negative (cyclin D1(-)) patients (log-rank test, P=0.0002; Wilcoxon test, P=0.0005), whereas p16-positive (p16(+)) patients had significantly better prognoses than p16-negative (p16(-)) patients (log-rank test, P=0.0063; Wilcoxon test, P=0.0044). The survival period was over 65% for patients with cyclin D1(-)/p16(+) (n=34) at 120 months after surgery, whereas patients with cyclin D1(+)/p16(-) patients (n=22) had a 50% survival period at 49 months. The cumulative survival rate of cyclin D1(+)/p16(-) patients was significantly lower than that of cyclin D1(-)/p16(+) patients (log-rank test, P=0.0004; Wilcoxon test, P=0.0002). The pRB did not influence significantly the survival rate. Our results indicate that cyclin D1 and p16, especially a combination of cyclin D1 and p16, are very useful to predict the prognosis of patient with NSCLC after curative resection independent of pathological stages I and II.     

Radiotherapy alone or with chemotherapy in the treatment of small-cell carcinoma of the lung: the results at 36 months. 2nd report to the Medical Research Council on the 2nd small-cell study.

This report compares the results at 36 months for 121 patients treated with radiotherapy alone (R) and 115 with radiotherapy followed by 3-drug chemotherapy (RC) for small-cell carcinoma of the lung of "limited" extent. The RC patients had an increased survival (P = 0.009 by log-rank test). The median survival was 25 weeks for the R patients and 43 weeks for the RC patients, but at 36 months, only 4 (3%) of the R patients and 5 (4%) of the RC patients were still alive. There was evidence of recurrence of the primary cancer in 41 (35%) of the 117 R and 35 (32%) of the 110 RC patients who died. Distant metastases were more frequent in the R series, being reported in 99 (82%) compared with 82 (71%) of the RC patients (P less than 0.05 by log-rank test). The numbers of R patients alive and considered free of metastases were 10 (8%) at 12 months, 3 (2%) at 24 months and 3 (2%) at 36 months; the corresponding figures for the RC patients being 30 (26%), 9 (8%), and 4 (3%).     

Impact of 5-fluorouracil rechallenge on subsequent response and survival in advanced colorectal cancer: pooled analysis from three consecutive randomized controlled trials

The aim of this analysis is to evaluate the effect of 5-fluorouracil (5-FU) rechallenge on subsequent response and survival in patients with advanced colorectal cancer (CRC). Between April 1992 and August 1998, 613 patients were enrolled into 3 consecutive prospective randomized controlled trials assessing first-line infused 5-FU in patients with advanced CRC. All patients had a planned maximum treatment period of 6 months. Those with responding or stable disease at the end of 6 months were observed off treatment. On subsequent disease progression, patients were retreated with 5-FU alone (5-FU group) or 5-FU plus mitomycin C (MMC group). Ninety-three patients have been retreated (5-FU group, n = 71; MMC group, n = 22). The median age was 60 years (range, 38-79 years), and the median time to rechallenge was 11.7 months (5-FU group, 11.7 months; MMC group, 11.4 months). Seventeen percent of patients had an objective response to rechallenge (5-FU group, 13%; MMC group, 27%). The median survival was 14.8 months (5-FU group, 15.2 months; MMC group, 10.5 months; log-rank test, P = 0.23) and the median failure-free survival was 5.4 months (5-FU group, 5.6 months; MMC group, 3.7 months; log-rank test, P = 0.06). On multivariate analysis, a prolonged treatment-free interval of > 12 months (hazard ratio [HR], 0.57; 95% CI, 0.35-0.94; P = 0.027) and good performance status of 0/1 (HR, 0.38; 95% CI, 0.22-0.68; P = 0.001) were associated with better overall survival. In conclusion, a proportion of patients who experienced a prolonged period of tumor control with first-line infused 5-FU therapy and had a planned treatment interruption, retained 5-FU sensitivity and had prolonged survival with 5-FU rechallenge.     

Gastric cancer: which patients benefit from systematic lymphadenectomy?

AIMS: The purpose of this study was to evaluate the value of systematic lymphadenectomy (SLA) in curative resected gastric cancer patients with respect to long-term survival, peri-operative morbidity and mortality. METHODS: We reviewed our prospectively gathered database of 309 resected gastric cancer patients and analysed the outcome of 185 R0-resected patients (60%) with respect to peri-operative morbidity, mortality and long-term survival by comparing 81 patients resected with SLA (D2-group) versus 104 patients resected without SLA (D1-group). RESULTS: Overall 5-year survival rates of R0-resected patients (n = 173; exclusion of peri-operative mortality) amounted to 49% and did not differ significantly between D2- and D1-groups (53% vs 47%); P=0.344). Nevertheless, subgroups of patients taking a benefit from SLA could be defined. Gastric cancer patients without LN metastases (pTx pN0; n=78) and patients with LN metastases only in perigastric lymph nodes (pTx pN1; n=34) showed a significantly better long-term prognosis when SLA was performed (84% vs 51%; P=0.001). Regarding peri-operative morbidity (38% vs 39%) and mortality (6% in each case) we could not find any differences between the D2- and D1-groups. CONCLUSIONS: We conclude that SLA is able to improve long-term survival for some tumour stages. Therefore SLA should be recommended as a standard procedure in all gastric cancer patients resected with curative intention.     

p53 and K-ras gene mutations correlate with tumor aggressiveness but are not of routine prognostic value in colorectal cancer.

PURPOSE: p53 gene and K-ras mutations are among the most common genetic alterations present in colorectal cancer. The prognostic utility of such mutations remains controversial. The purpose of this study was to prospectively evaluate the prognostic significance of p53 and K-ras gene mutations in colorectal cancer. PATIENTS AND METHODS: One hundred forty patients were analyzed. Tumors belonging to the microsatellite mutator phenotype were excluded (n = 8). Mutations at the K-ras and p53 genes were detected and characterized by restriction fragment length polymorphism, single-strand conformation polymorphism, and sequencing, as appropriate. RESULTS: p53 mutations were detected in 66 (50%) and K-ras mutations were detected in 54 (41%) of the 132 patients. In 26 cases (20%), ras and p53 mutations coexisted; in 38 cases (29%), neither mutation was found. Multivariate analysis of the whole population analyzed (n = 132) showed that survival was strongly correlated with the presence of p53 mutations alone or in combination with K-ras mutations (P = .002; log-rank test). When only patients undergoing a radical resection were considered (R0; n = 101), p53 mutations were no longer of prognostic significance. CONCLUSION: p53 mutations alone or in combination with K-ras mutations are correlated with a worse outcome. However, the routine use of these mutations as prognostic markers in the clinical setting is not recommended.     

Tumor-associated alterations in caspase-14 expression in epithelial malignancies.

PURPOSE: Caspase-14 is unique among caspase family proteases in that its proteolytic processing has been principally associated with epithelial cell differentiation rather than apoptosis or inflammation. We investigated caspase-14 expression in several types of human epithelial malignancy by immunohistochemistry, correlating results with stage, histologic grade, and patient survival. EXPERIMENTAL DESIGN: Tumor-associated alterations in caspase-14 expression were observed for cervical, ovarian, breast, gastric, and colon cancers. RESULTS: In cervical (n = 445), ovarian (n = 91), and colon (n = 106) specimens, expression of caspase-14 was significantly reduced in cancers compared with normal epithelium. Decreases in caspase-14 immunopositivity correlated with the histologic progression of cervical cancer (P < 0.0001, ANOVA). In localized gastric cancers, caspase-14 immunostaining was significantly lower in poorly differentiated tumors compared with well-differentiated tumors (P = 0.02, Pearson's chi(2) analysis). Lower caspase-14 expression was associated with advanced clinical stage in ovarian cancer (P = 0.04, ANOVA) and with shorter overall survival among ovarian cancer patients with serous tumors (n = 62) in both univariate (P = 0.005) and multivariate (P = 0.03) analysis. Lower caspase-14 expression correlated with shorter overall survival among patients with T(3)N(0)M(0) stage gastric cancers (n = 94; P = 0.006, log-rank test). In contrast to cervical, ovarian, and colon cancers, caspase-14 expression was increased in ductal carcinoma in situ and invasive cancers compared with normal mammary epithelium (P = 0.001, t test). CONCLUSIONS: The findings reveal tumor-specific alterations in caspase-14 expression and suggest that differences in its expression may define subsets of epithelial cancers with distinct clinical behaviors.     

Mutagen sensitivity as a biomarker for second primary tumors after head and neck squamous cell carcinoma.

The occurrence of second primary tumors after curative treatment of early stage head and neck squamous cell carcinoma negatively influences the overall survival. Our aim was to prospectively evaluate whether mutagen sensitivity (mean number of chromatid breaks per cell in cultured lymphocytes exposed to bleomycin) could be used as a biomarker to predict which patients will develop second malignancies in the respiratory or upper digestive tract. Patients treated for head and neck squamous cell carcinoma (n = 218) were followed for approximately 6 years. Nineteen patients developed a second primary tumor, and each of these patients was matched on age, gender, cumulative smoking, tumor site, and tumor stage to two patients who did not develop any second malignancy. No difference between the groups was found with respect to mutagen sensitivity. Smoking at the time of the index tumor had a significant influence on the occurrence of second primary tumors (log-rank, P = 0.019). There was a significantly (P = 0.005) higher mean breaks-per-cell value in those patients who had developed their second primary tumor > or = 3 years after the first tumor (0.97 +/- 0.24; n = 10) compared with early second primary tumor patients (0.69 +/- 0.09; n = 9). Conditional on a more than 3-year second primary tumor-free survival (n = 38), there is a significantly (log-rank, P = 0.036) higher probability of a second primary tumor for mutagen-sensitive patients [relative risk, 7.8 (95% confidence interval, 0.99-61.74; P = 0.05)]. Mutagen sensitivity is a potential biomarker for the occurrence of 'late' second malignancies (> 3 years between tumors), and additional studies on the inclusion of this biomarker in chemoprevention trials is commendable because it would greatly improve their efficiency.     

Surgical management and outcome of metachronous Krukenberg tumors from gastric cancer

BACKGROUND AND OBJECTIVES: The question of whether resection should be performed in Krukenberg tumors from gastric cancer has yet to be adequately examined. Despite some reports on the surgical treatment of Krukenberg tumors, the outcomes after resection are not well characterized. PATIENTS AND METHODS: Using a gastric cancer database, a total of 34 patients who underwent a resection of metastatic ovarian tumors after curative surgery for gastric cancer were identified. A prospective database of these patients was reviewed for the presentation, clinical features, and outcomes after resection. RESULTS: The median age of 34 patients was 44 years (range, 24-66). The majority of patients was in the premenopausal state and had bilateral ovarian involvement. The most common presenting symptom was an abdominal mass (35.3%). Tumor size ranged from 3.5 to 20 cm with 61.8% measuring larger than 10 cm. In 17 patients who had metastatic disease confined to the pelvis, a complete gross resection (R0) was achieved. In the other 17 with the disease beyond the pelvis gross residual tumors remained after the resection (R1). The median survival of all patients was 11 months (95% confidence interval [CI] 8-14), and that of the patients rendered R0 was 18 months (95% CI, 14-22), in comparison with 9 months (95% CI, 3-15) for those with R1 resection (P = 0.0001; log-rank test). The median progression free survival was also significantly longer for the patients with R0 resection than those with R1 resection (8 months, 95% CI, 5-11 vs. 5 months, 95% CI, 4-6, P = 0.0103). Multivariate analysis identified R0 resection as the only significant factor predictive of survival. CONCLUSIONS: In the management of Krukenberg tumors after gastric cancer, a metastasectomy may significantly improve the overall and progression free survival if it could render a complete gross resection. To define the patient group that benefits most from resection, the extent of disease and resectability must be carefully evaluated before surgery.     

Overall survival analysis of neoadjuvant chemoradiotherapy and esophagectomy for esophageal cancer

Background

Patients treated with neoadjuvant chemoradiotherapy (NAC) followed by esophagectomy are more likely to have negative margins at resection, be downstaged, and have improved overall survival (OS). The specific aim of this study was to analyze OS outcomes using NAC followed by esophagectomy at a single, tertiary care academic medical center.

Methods

We retrospectively analyzed 106 patients that underwent NAC with platinum-based chemotherapy plus 5-fluorouracil (5-FU) or capecitabine followed by esophagectomy from September 1996 to May 2011. OS was analyzed by the Kaplan Meier method.

Results

Initial staging determined that of 106 patients, 62% had stage III (n=66), 31% stage II (n=33), and 7% had stage I disease (n=7). Following NAC, 92.5% (n=98) were resected with negative (R0) margins and pathologic staging revealed 59% (n=62) were downstaged, 9% (n=10) were upstaged, and 32% (n=34) remained at the same stage. A pathologic complete response (pCR) was achieved in 29% (n=31) of the cohort. Median OS was 35.2 months for all patients, 42 months for downstaged patients, 13 months when upstaged, and 17 months for those who remained at the same stage (P=0.08). OS by histological type was 30 months for adenocarcinoma and 71 months for squamous cell carcinoma (P=0.06).

Conclusions

NAC was effective in downstaging 59% of patients and effectively increased the chance for an R0 resection. These patients, in turn, had improved OS compared to the median OS. Patients with squamous cell carcinoma showed a trend towards more favorable OS.     

Phase III study comparing cisplatin plus fluorouracil to paclitaxel, cisplatin, and fluorouracil induction chemotherapy followed by chemoradiotherapy in locally advanced head and neck cancer.

PURPOSE: To compare the antitumor activity and toxicity of the two induction chemotherapy treatments of paclitaxel, cisplatin, and fluorouracil (FU; PCF) versus standard cisplatin and FU (CF), both followed by chemoradiotherapy (CRT), in locally advanced head and neck cancer (HNC). PATIENTS AND METHODS: Eligibility criteria included biopsy-proven, previously untreated, stage III or IV locally advanced HNC. Patients received either CF (cisplatin 100 mg/m2 on day 1 plus FU 1000 [corrected] mg/m2 continuous infusion on days 1 through 5) or PCF (paclitaxel 175 mg/m2 on day 1, cisplatin 100 mg/m2 on day 2, and FU 500 mg/m2 continuous infusion on days 2 through 6); both regimens were administered for three cycles every 21 days. Patients with complete response (CR) or partial response of greater than 80% in primary tumor received additional CRT (cisplatin 100 mg/m2 on days 1, 22, and 43 plus 70 Gy). RESULTS: A total of 382 eligible patients were randomly assigned to CF (n = 193) or PCF (n = 189). The CR rate was 14% in the CF arm v 33% in the PCF arm (P < .001). Median time to treatment failure was 12 months in the CF arm compared with 20 months in the PCF arm (log-rank test, P = .006; Tarone-Ware, P = .003). PCF patients had a trend to longer overall survival (OS; 37 months in CF arm v 43 months in PCF arm; log-rank test, P = .06; Tarone-Ware, P = .03). This difference was more evident in patients with unresectable disease (OS: 26 months in CF arm v 36 months in PCF arm; log-rank test, P = .04; Tarone-Ware, P = .03). CF patients had a higher occurrence of grade 2 to 4 mucositis than PCF patients (53% v 16%, respectively; P < .001). CONCLUSION: Induction chemotherapy with PCF was better tolerated and resulted in a higher CR rate than CF. However, new trials that compare induction chemotherapy plus CRT versus CRT alone are needed to better define the role of neoadjuvant treatment.     

胸段食管鳞癌术前同步放化疗不同放疗分割方式的临床研究

目的 评价术前大分割放疗与常规分割放疗治疗胸段食管鳞癌的疗效和安全性。方法 2002—2011年四川省肿瘤医院收治的行术前放化疗的胸段食管鳞癌共86例,根据术前放疗分割方式分为大分割放疗组(A组,41例,30 Gy分10次2周)和常规分割放疗组(B组,45例,40 Gy分20次4周),放疗结束后2—6周手术。Kaplan-Meier法计算生存并Logrank检验。结果 A组与B组病理降期率分别为68%和56%(P=0.270),R0切除率分别为95%和89%(P=0.437),pCR率分别为32%和24%(P=0.480)。A组和B组1、3、5年OS分别为78%和69%、44%和44%,29%和33%(P=0.114、0.223、0.289),PFS分别为71%和62%、39%和38%、24%和29%(P=0.211、0.689、0.331)。两组患者放化疗和手术相关不良反应相近(P=0.089~0.872)。大分割放疗组在平均住院天数、放疗费用及术前治疗总费用上均明显低于常规放疗组(P=0.000、0.000、0.000)。结论 术前大分割放疗和常规放疗均可作为可切除胸段食管鳞癌术前放疗的选择方案。术前大分割放疗有治疗周期和住院时间短,放疗费用低,患者更易接受的优势。     

Ⅱ期上呼吸消化道结外鼻型NK/T细胞淋巴瘤患者受累区域淋巴结水平的预后价值

目的 分析区域淋巴结转移范围在Ⅱ期上呼吸消化道结外鼻型NK/T细胞淋巴瘤(UADT-NKTCL)患者中的预后价值。方法 回顾分析1987—2013年间本院初治的97例Ⅱ期UADT-NKTCL患者资料,分析淋巴结转移范围与预后关系。全组患者52例原发鼻腔,45例原发鼻腔外上呼吸消化道。多数患者接受以放疗为主治疗,65例接受放化疗,27例单纯放疗,5例单纯化疗。Kaplan-Meier法计算生存率,Logrank法检验和单因素预后分析,Cox模型多因素分析。结果 全组患者5年OS、PFS分别为57%、49%。单因素和多因素分析都显示伴有下颈(环状软骨下缘水平以下)淋巴结转移的患者预后更差,其中位生存时间仅19.3个月,2、5年OS分别为28%、11%,而未伴有下颈淋巴结受累的Ⅱ期患者5年OS达68%(P=0.000)。治疗模式明显影响预后,综合治疗患者5年OS、PFS分别为64%、52%,显著优于单纯放疗或化疗患者的40%(P=0.006)和42%(P=0.088)。结论 区域淋巴结受累水平是Ⅱ期UADT-NKTCL的独立预后因素,伴有下颈淋巴结受累患者预后很差。     

Exclusive radical surgery for esophageal adenocarcinoma

BACKGROUND: Because very poor survival rates were reported after exclusive nonradical surgery, the current opinion in the medical community is that very few esophageal adenocarcinoma patients can anticipate long-term survival after esophagectomy. In the current study the ability of exclusive radical surgery including very extended lymph node dissection to provide a substantial percentage of patients with long-term survival was examined. METHODS: Radical esophagectomy (including removal of the esophageal tube, excision of the potentially involved locoregional lymph nodes, and skeletization of the nonresectable vital organs in the mediastinum and upper abdomen) was attempted in 183 consecutive patients with either Barrett (n = 77) or non-Barrett (n = 106) adenocarcinoma of the esophagus or cardia. Esophagectomy was subtotal (neck anastomosis) or distal (chest anastomosis) in 103 patients and 80 patients, respectively. RESULTS: Radical esophagectomy (Ro resection) was feasible in 137 patients (75%) whereas 46 patients (25%) in whom a part of the neoplastic process was not resectable (R1 or R2 resection) underwent a palliative esophagectomy. The 5-year survival, including in-hospital deaths (4.3%), was 35.3% for the whole series, 48% after Ro resection, and 0% after R1 or R2 resection. The 5-year survival rate after any R resection was 57.2% in patients with Barrett adenocarcinoma compared with 20% in patients with non-Barrett adenocarcinoma (P < 0.0001) because of a higher prevalence of nontransmural tumors (Tis through T2, N0) in the former group (56.5%) compared with the latter group (6.6%) (P < 0.0001). The 5-year survival was related closely to the magnitude of both wall penetration and extraesophageal neoplastic spread (Ro, Tis-T1-T2, N0 = 83.5% vs. Ro, T3, N0 = 44.4% vs. Ro, any T, N1 < 5 metastatic lymph nodes = 37% vs. Ro, any T, N1 > or = 5 metastastic lymph nodes = 6.8% vs. R1, R2 = 0%; P < 0.0001). CONCLUSIONS: Exclusive radical esophagectomy provides a chance of long-term survival in 35% of esophageal adenocarcinoma patients in whom it is attempted and nearly 50% of those patients in whom it is feasible. The presence of a small number of metastatic lymph nodes does not appear to preclude a long-term favorable outcome.