The additional value of chemotherapy to radiotherapy in locally advanced nasopharyngeal carcinoma: a meta-analysis of the published literature.

PURPOSE: The purpose of this meta-analysis was to determine the additional value of neoadjuvant, concurrent, and/or adjuvant chemotherapy to radiation in the treatment of locally advanced nasopharyngeal carcinoma (NPC) with regard to the overall survival (OS) and the incidence of local-regional recurrences (LRR) and distant metastases (DM). PATIENTS AND METHODS: To be eligible, full published studies had to deal with biopsy-proven NPC and have patients randomly assigned to receive conventional radiotherapy (66 to 70 Gy in 7 weeks) or radiotherapy combined with chemotherapy. RESULTS: Ten randomized clinical studies were identified, including 2,450 patients. The pooled hazard ratio (HR) of death for all studies was 0.82 (95% CI, 0.71 to 0.95; P = .01) corresponding to an absolute survival benefit of 4% after 5 years. Three categories of trials were defined according to the sequence of chemotherapy, including neoadjuvant chemotherapy, at least concomitant chemoradiotherapy, and adjuvant chemotherapy. A significant interaction term (P = .02) was found among these three categories. The largest effect was found for concomitant chemotherapy, with a pooled HR of 0.48 (95% CI, 0.32 to 0.72), which corresponds to a survival benefit of 20% after 5 years. Comparable results were found for the incidence of LRR and DM. CONCLUSION: The results of this study indicate that concomitant chemotherapy in addition to radiation is probably the most effective way to improve OS in NPC.     

Survival benefits from neoadjuvant chemoradiotherapy or chemotherapy in oesophageal carcinoma: a meta-analysis

BACKGROUND: Resectable oesophageal cancer is often treated with surgery alone or with preoperative (neoadjuvant) chemoradiotherapy or chemotherapy. We aimed to clarify the benefits of neoadjuvant chemoradiotherapy or chemotherapy versus surgery alone by a meta-analysis of randomised trial data. METHODS: Eligible trials were identified first from earlier published meta-analyses and systematic reviews. We also used MEDLINE, Cancerlit, and EMBASE databases to identify additional studies and published abstracts from major scientific meetings since 1980. Only randomised studies with an analysis by an intention-to-treat principle were included, and searches were restricted to those databases citing articles in English. We used published hazard ratios if available or estimates from other survival data or survival curves. Treatment effects by type of tumour and treatment sequencing were also investigated. FINDINGS: Ten randomised comparisons of neoadjuvant chemoradiotherapy versus surgery alone (n=1209) and eight of neoadjuvant chemotherapy versus surgery alone (n=1724) in patients with local operable oesophageal carcinoma were identified. The hazard ratio for all-cause mortality with neoadjuvant chemoradiotherapy versus surgery alone was 0.81 (95% CI 0.70-0.93; p=0.002), corresponding to a 13% absolute difference in survival at 2 years, with similar results for different histological tumour types: 0.84 (0.71-0.99; p=0.04) for squamous-cell carcinoma (SCC), and 0.75 (0.59-0.95; p=0.02) for adenocarcinoma. The hazard ratio for neoadjuvant chemotherapy was 0.90 (0.81-1.00; p=0.05), which indicates a 2-year absolute survival benefit of 7%. There was no significant effect on all-cause mortality of chemotherapy for patients with SCC (hazard ratio 0.88 [0.75-1.03]; p=0.12), although there was a significant benefit for those with adenocarcinoma (0.78 [0.64-0.95]; p=0.014). INTERPRETATION: A significant survival benefit was evident for preoperative chemoradiotherapy and, to a lesser extent, for chemotherapy in patients with adenocarcinoma of the oesophagus. The findings provide an evidence-based framework for the use of neoadjuvant treatment in management decisions.     

Individual patient data meta-analyses in head and neck carcinoma: what have we learnt?]

Carcinoma of the upper aerodigestive tract (oral cavity, oropharynx, hypopharynx, nasopharynx, larynx) are frequent tumors for which surgery and/or radiotherapy are the main therapeutic agents. The main results of meta-analyses based on the collection of individual patients data are reported: 1) The meta-analysis on chemotherapy, regrouping data of nearly 11,000 patients issued from 63 randomized trials showed an absolute benefit of 4% at five years in overall survival, in favor of chemotherapy (P<0.0001). Most of the benefit was seen with concomitant radiochemotherapy, however with a relatively large heterogeneity in this subgroup of trials. An update of this meta-analysis was performed including 24 additional trials, which confirmed the magnitude of the benefit due to concomitant chemotherapy (8% at 5 years). 2) The meta-analysis on larynx preservation, using induction chemotherapy in larynx and hypopharynx carcinomas. No significant difference was seen between the control arm with total laryngectomy and the larynx preservation approach. 3) The meta-analysis on chemotherapy in nasopharynx carcinomas, from the data of 11 randomized trials including 2722 patients, and comparing the radiotherapy to radio-chemotherapy (1979-2001). The results showed an absolute benefit of 6% at five years in overall survival, in favor of chemotherapy (P<0.0001). Most of the benefit was seen with concomitant radiochemotherapy. 4) Finally, a meta-analysis on altered fractionated RT, compared to conventional RT in 15 randomized trials regrouping 6515 patients. The results showed a small but significant improvement in favor of altered fractionated RT for overall survival and local control with an absolute benefit at five years of 3 and 6%, respectively.     

Neoadjuvant chemotherapy and radiation therapy compared with radiation therapy alone in advanced nasopharyngeal carcinoma

PURPOSE: To analyze the impact of neoadjuvant chemotherapy on the treatment of locoregionally advanced nasopharyngeal carcinoma and to assess the outcomes of patients receiving such treatment. METHODS AND MATERIALS: We analyzed 137 previously untreated and histologically confirmed advanced stage nasopharyngeal carcinoma patients treated with either radiation therapy only or combined radiation therapy and chemotherapy at the Seoul National University Hospital between 1984 and 1996. The stage distribution was as follows: AJCC Stage III-21, Stage IV-61 in the radiation therapy group (RT group); AJCC Stage III-1, Stage IV-54 in neoadjuvant chemotherapy and radiation therapy group (CT/RT group). The median follow-up for surviving patients was 48 months. RESULTS: The 5-year overall survival (OS) rates were 71% for the CT/RT group and 59% for the RT group (p = 0.04). The 5-year actuarial disease-free survival (DFS) rates were 63% for the CT/RT group and 52% for the RT group (p = 0.04). Distant metastasis (DM) incidence was significantly lower in the CT/RT group. The 5-year freedom from distant metastasis rates were 84% for the CT/RT group and 66% for the RT group (p = 0.01). The incidence of locoregional failures was also lower in the CT/RT group, although this difference did not reach statistical significance (69% vs. 56%, p = 0.09) CONCLUSION: While not providing conclusive evidence, historical evidence from this institution suggests that neoadjuvant chemotherapy significantly improves both overall and the disease-free survival of patients with advanced stage nasopharyngeal carcinoma.     

Results of a prospective randomized trial comparing neoadjuvant chemotherapy plus radiotherapy with radiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma.

PURPOSE: A prospective randomized trial was performed to evaluate the contribution of neoadjuvant chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma. PATIENTS AND METHODS: Patients with locoregionally advanced nasopharyngeal carcinoma were treated either with radiotherapy alone (RT group) or neoadjuvant chemotherapy plus radiotherapy (CT/RT group). Neoadjuvant chemotherapy consisting of two to three cycles of cisplatin (100 mg/m(2), day 1), bleomycin (10 mg/m(2), days 1 and 5), and fluorouracil (5-FU; 800 mg/m(2), days 1 through 5, continuous infusion) followed by radiotherapy was given to the CT/RT group. All patients were treated in a uniform fashion by definitive-intent radiation therapy in both groups. RESULTS: Between July 1993 and July 1994, 456 patients were entered onto the study, with 228 patients randomized to each treatment arm, and 449 patients (225 in the RT group and 224 in the CT/RT group) were assessable. All 456 patients were included in survival analysis according to the intent-to-treat principle. The 5-year overall survival (OS) rates were 63% for the CT/RT group and 56% for the RT group (P =.11). The median relapse-free survival (RFS) time was 50 months for the RT group and not reached for the CT/RT group. The 5-year RFS rate was 49% for the RT group versus 59% for the CT/RT group (P =.05). The 5-year freedom from local recurrence rate was 82% for the CT/RT group and 74% for the RT group (P =.04). There was no significant difference in freedom from distant metastasis between the two treatment groups (CT/RT group, 79%; RT group, 75%; P =.40). CONCLUSION: This randomized study failed to demonstrate any significant survival benefit with the addition of neoadjuvant chemotherapy for patients with locoregionally advanced nasopharyngeal carcinoma. Therefore, neoadjuvant chemotherapy for nasopharyngeal carcinoma should not be used outside of the context of a clinical trial.     

Nasopharyngeal carcinoma in children: ten years' experience at the Tata Memorial Hospital, Mumbai

PURPOSE: To evaluate the disease characteristics and outcome of children with nasopharyngeal carcinoma treated at the Tata Memorial Hospital, Mumbai. METHODS AND MATERIALS: Between 1990 and 2000, 81 pediatric patients with a diagnosis of nasopharyngeal carcinoma were treated at the Tata Memorial Hospital. The median age was 14 years. The male/female ratio was 2.8:1. Of the 81 patients, 32 (39%), 21 (26%), and 28 (35%) had T1-T2, T3, and T4 (TNM International Union Against Cancer staging system, 1997), respectively. Ninety-one percent presented with nodal metastasis. Thirty patients (37%) had lymph nodes >6 cm, and 45 (56%) had bilateral nodes at presentation. Histologically, 77 patients (95%) had undifferentiated carcinoma. Eighty-five percent received neoadjuvant multiagent chemotherapy containing bleomycin, methotrexate, and cisplatin, followed by radiotherapy (RT). RESULTS: After a median follow-up of 50 months, the disease-free survival (DFS) and overall survival (OS) rate for the entire group was 45% and 54%, respectively. Kaplan-Meier curves were used for evaluation of prognostic factors and were compared using the log-rank test. Nodal status had a significant impact on DFS (p = 0.021) and OS (p = 0.006). Complete responders to chemotherapy had superior DFS (p = 0.000) and OS (p = 0.000). RT doses >60 Gy resulted in better DFS (p = 0.020) and OS (p = 0.012). Combined chemotherapy plus RT resulted in improved DFS (p = 0.457) and OS (p = 0.296), although the difference was not statistically significant. CONCLUSION: Combined modality management using chemotherapy and RT resulted in satisfactory locoregional control and OS in pediatric patients with nasopharyngeal carcinoma. Nodal involvement, response to chemotherapy, and RT dose were important prognostic factors.     

Prognostic and predictive effects of immunohistochemical factors in high-risk primary breast cancer patients.

PURPOSE: To analyze prognostic and predictive effects of immunohistochemical factors within a randomized study of high-dose versus standard-dose chemotherapy in high-risk breast cancer with >10 involved lymph nodes. EXPERIMENTAL DESIGN: Histopathologic specimens in 188 of 302 patients were analyzed for Ki-67, p16, maspin, Bcl-2, Her2/neu, and p53. RESULTS: In a univariate analysis after adjustment for therapy, tumor size, and estrogen receptor, Her2/neu positivity (P = 0.001) was a negative and Bcl2 positivity (P = 0.003) was a positive prognostic factor for event-free survival. In a multivariate analysis, Her2/neu positivity (hazard ratio, 3.68; 95% confidence interval, 2.01-6.73; P = 0.0001) had a negative influence on event-free survival, whereas p53 positivity (hazard ratio, 0.57; 95% confidence interval, 0.34-0.95; P = 0.03) and Bcl2 positivity (hazard ratio, 0.35; 95% confidence interval, 0.19-0.64; P = 0.0006) were associated with a better event-free survival. Analyzing the predictive effect of the immunohistochemical factors, an interaction between p53 and treatment could be shown (P = 0.005). The hazard ratio for high-dose chemotherapy versus standard chemotherapy is estimated as 2.3 (95% confidence interval, 0.67-7.92) in p53-negative patients and as 0.46 (95% confidence interval, 0.2-1.07) in p53-positive patients, which indicates a superiority of high-dose chemotherapy in p53-positive patients and an inferiority in p53-negative patients. No interactive effect could be shown for the other factors. CONCLUSIONS: Her2/neu and Bcl-2 are prognostic but not predictive factors in patients with high-risk primary breast cancer; p53-positive patients might benefit more from high-dose chemotherapy than from standard chemotherapy, and p53-negative patients might benefit more from standard chemotherapy than from high-dose therapy.     

High-dose versus conventional-dose chemotherapy as first-salvage treatment in patients with non-seminomatous germ-cell tumors: a matched-pair analysis.

BACKGROUND: The purpose of this study was to compare high-dose chemotherapy (HDCT) with conventional-dose chemotherapy (CDCT) as first-salvage treatment in patients with relapsed or refractory non-seminomatous germ-cell tumors (NSGCT). PATIENTS AND METHODS: One hundred and ninety-three patients with relapsed or refractory NSGCT, between 1981 and 1995, were identified from two large databases. In 74 of these, intensification of first-salvage treatment by HDCT was planned. Patients were matched based on primary tumor location, response to first-line treatment, duration of this response and serum levels of the tumor markers, human chorionic gonadotrophin (HCG) and alpha-fetoprotein (AFP). Multivariate analyses were performed using event-free survival and overall survival as primary endpoints. RESULTS: Full matches on all five factors were found for 38 pairs of patients; for a further 17 pairs, matches on at least four factors could be identified. Hazard ratios in favor of HDCT were obtained between 0.72 and 0.84 [confidence interval (CI) 0.59-1.01] for event-free survival and between 0.77 and 0.83 (CI 0.60-0.99) for overall survival, depending on the type of analysis. CONCLUSIONS: The current analysis suggests a benefit from HDCT, with an estimated absolute improvement in event-free survival of between 6 and 12% and in overall survival of between 9 and 11% at 2 years. This benefit is lower than expected from previous phase I/II studies.     

Gender Differences and Their Effects on Survival Outcomes in Lung Cancer Patients Treated With PD-1/PD-L1 Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

AimsProgrammed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1) immune checkpoint inhibitors have had a major impact on the approach to care of patients with lung cancer. An important issue that is not known is whether they benefit men and women the same. We conducted a meta-analysis of all randomised controlled trials evaluating PD-1/PD-L1 inhibition in patients with non-small cell lung cancer (NSCLC) to determine if clinical response and survival are influenced by gender.Materials and methodsA PubMed search was carried out to identify all randomised controlled trials evaluating PD-1/PD-L1 inhibitors compared with conventional chemotherapy in NSCLC. Random-effects meta-analysis and meta-regression were performed to assess overall survival and progression-free survival (PFS) and whether there were differences in these outcomes between men and women.ResultsIn total, 12 studies with data for overall survival and 11 studies with data for PFS were included. Immunotherapy showed a statistically significant benefit over chemotherapy for overall survival (pooled hazard ratio = 0.72, 95% confidence interval = 0.65–0.81, P < 0.001) and progression-free survival (pooled hazard ratio = 0.62, 95% confidence interval = 0.54–0.72, P < 0.001). We did not find a statistically significant difference between men and women in terms of overall survival (males versus females: pooled hazard ratio = 0.74, 95% confidence interval = 0.66–0.83 versus pooled hazard ratio = 0.72, 95% confidence interval = 0.63–0.82, P = 0.709) or progression-free survival (males versus females: pooled hazard ratio = 0.63, 95% confidence interval = 0.53–0.75 versus pooled hazard ratio = 0.72, 95% confidence interval = 0.58–0.88, P = 0.372).ConclusionThis is the first systematic review and meta-analysis investigating the effect of gender and response to PD-1/PD-L1 checkpoint inhibitors in patients solely with NSCLC. We examined 9270 and 6193 patients in terms of overall survival and PFS, respectively. Although there are significant biological differences between men's and women's immune responses, we have shown that these drugs offer the same survival benefit in patients with NSCLC regardless of gender.     

Editor's choice: Practice changing mature results of RTOG study 9802: another positive PCV trial makes adjuvant chemotherapy part of standard of care in low-grade glioma

The long-term follow-up of the RTOG 9802 trial that compared 54 Gy of radiotherapy (RT) with the same RT followed by adjuvant procarbazine, CCNU, and vincristine (PCV) chemotherapy in high-risk low-grade glioma shows a major increase in survival after adjuvant PCV chemotherapy. Median overall survival increased from 7.8 years to 13.3 years, with a hazard ratio of death of 0.59 (log rank: P = .002). This increase in survival was observed despite the fact that 77% of patients who progressed after RT alone received salvage chemotherapy. With this outcome, RT + PCV is now to be considered standard of care for low-grade glioma requiring postsurgical adjuvant treatment. Unfortunately, studies on molecular correlates associated with response are still lacking. This is now the third trial showing benefit from the addition of PCV to RT in grade II or III diffuse glioma. The optimal parameter for selecting patients for adjuvant PCV has not yet been fully elucidated, but several candidate markers have so far emerged. It is still unclear whether temozolomide can replace PCV and whether initial management with chemotherapy only is a safe initial treatment. Potentially, that may adversely affect overall survival, but concerns for delayed RT-induced neurotoxicity may limit acceptance of early RT in patients with expected long term survival. The current evidence supports that in future trials, grades II and III tumors with similar molecular backgrounds should be combined, and trials should focus on molecular glial subtype regardless of grade.     

Myeloablative megatherapy with autologous stem-cell rescue versus oral maintenance chemotherapy as consolidation treatment in patients with high-risk neuroblastoma: a randomised controlled trial

BACKGROUND: Myeloablative megatherapy is commonly used to improve the poor outlook of children with high-risk neuroblastoma, yet its role is poorly defined. We aimed to assess whether megatherapy with autologous stem-cell transplantation could increase event-free survival and overall survival compared with maintenance chemotherapy. METHODS: 295 patients with high-risk neuroblastoma (ie, patients with stage 4 disease aged older than 1 year or those with MYCN-amplified tumours and stage 1, 2, 3, or 4S disease or stage 4 disease and <1 year old) were randomly assigned to myeloablative megatherapy (melphalan, etoposide, and carboplatin) with autologous stem-cell transplantation (n=149) or to oral maintenance chemotherapy with cyclophosphamide (n=146). The primary endpoint was event-free survival. Secondary endpoints were overall survival and the number of treatment-related deaths. Analyses were done by intent to treat, as treated, and treated as randomised. FINDINGS: Intention-to-treat analysis showed that patients allocated megatherapy had increased 3-year event-free survival compared with those allocated maintenance therapy (47% [95% CI 38-55] vs 31% [95% CI 23-39]; hazard ratio 1.404 [95% CI 1.048-1.881], p=0.0221), but did not have significantly increased 3-year overall survival (62% [95% CI 54-70] vs 53% [95% CI 45-62]; 1.329 [0.958-1.843], p=0.0875). Improved 3-year event-free survival and 3-year overall survival were also recorded for patients given megatherapy in the as-treated group (n=212) and in the treated-as-randomised group (n=145). Two patients died from therapy-related complications during induction treatment. No patients given maintenance therapy died from acute treatment-related toxic effects. Five patients given megatherapy died from acute complications related to megatherapy. INTERPRETATION: Myeloablative chemotherapy with autologous stem-cell transplantation improves the outcome for children with high-risk neuroblastoma despite the raised risk of treatment-associated death.     

Long-term follow-up of the Stockholm randomized trials of postoperative radiation therapy versus adjuvant chemotherapy among 'high risk' pre- and postmenopausal breast cancer patients

For many years, loco-regional radiotherapy was the standard postoperative treatment for node positive breast cancer patients in Sweden. Because of encouraging results from trials of adjuvant chemotherapy in the mid 1970s, the Stockholm Breast Cancer Study Group decided to directly compare postoperative radiation (RT) with adjuvant CMF-type chemotherapy (CT). Long-term results are presented from two randomized trials of RT versus CT in pre- (n = 547) and postmenopausal (n = 679) patients, respectively, with node positive disease or a tumour diameter > 30 mm. RT substantially reduced loco-regional recurrences among both pre- and postmenopausal patients (relative hazard RT versus CT: 0.67 and 0.43, respectively). Among premenopausal patients distant metastases occurred less frequently in the CT group (relative hazard: 1.68, p > 0.001) resulting in an improved recurrence-free survival (p = 0.04). Overall survival was also better with CT (cumulative survival at 15 years: 50% and 44% in the CT and RT groups, respectively) but the difference was not statistically significant. Among the postmenopausal patients there were no substantial differences in terms of recurrence-free or overall survival between the treatment groups. The risk of a second primary malignancy, however, was doubled in the RT group (p > 0.01). The most pronounced excess concerned second lung cancers occurring after 10 years. The cumulative incidence at 20 years was estimated at 0.3% and 3.7% in the CT and RT groups, respectively. The trials illustrate the role of radiotherapy in preventing loco-regional recurrences among high-risk patients, as well as the need for systemic treatment to control the disease systemically.     

Improvement of survival after addition of induction chemotherapy to radiotherapy in patients with early-stage nasopharyngeal carcinoma: Subgroup analysis of two Phase III trials

PURPOSE: Induction chemotherapy has not been shown to improve survival in nasopharyngeal carcinoma (NPC) in Phase III trials. To evaluate the effect of induction chemotherapy in NPC further, we performed subgroup analysis of two Phase III trials according to the T and N stage. METHODS AND MATERIALS: Data from two phase III trials comparing cisplatin/epirubicin or cisplatin/bleomycin/5-fluorouracil followed by radiotherapy (RT) vs. RT alone in NPC were pooled together for analysis. Patients were stratified into four subgroups according to the 1997 American Joint Committee on Cancer T and N stage: T1-T2N0-N1, Group 1 (early-stage disease); T1-T2N2-N3, Group 2 (advanced N disease); T3-T4N0-N1, Group 3 (advanced T stage); and T3-T4N2-N3, Group 4 (advanced T and N disease). Group 1 consisted entirely of patients with Stage IIB disease. A total of 784 patients were included for analysis on an intent-to-treat basis. The median follow-up for the surviving patients was 67 months. RESULTS: No significant differences in overall survival, locoregional failure-free, or distant metastasis-free rates were observed between the combined and RT arms in Groups 2 to 4. Significant differences in the overall survival and distant metastasis-free rates were observed only in Group 1, favoring the combined chemotherapy and RT arm. The 5-year overall survival rate was 79% in the combined arm and 67% in the RT-alone arm (p = 0.048). The corresponding 5-year distant metastasis-free rates were 86% and 74% (p = 0.0053). CONCLUSIONS: Our results have shown that patients in Group 1, with early-stage NPC treated by RT alone, had relatively poor survival because of distant metastases. The observation of improved outcomes in this subgroup after the addition of induction chemotherapy has not been previously reported and warrants additional investigation.     

鼻咽癌调强放疗时代诱导化疗后序贯放疗±同步化疗疗效与安全性的Meta分析

目的 Meta分析调强放疗时代鼻咽癌诱导化疗(IC)联合单纯放疗(RT)与诱导化疗联合同步放化疗(CCRT)的疗效和不良反应。方法 选择已经发表的回顾性或者随机对照临床研究,检索Cochrane图书馆、PubMed、Web of Science数据库,以2010—2020年发表的研究为主要研究对象。选择的研究包括接受IC+CCRT或IC+RT治疗的鼻咽癌患者,使用STATA 12软件合并风险比(HR)、危险比(RR)及95%可信区间(CI),并应用随机或固定效应模型进行统计学分析。结果 共纳入了8项回顾性研究中的 2483例患者。IC+CCRT组与IC+RT组总生存相仿(HR=0.78,95%CI为 0.58~1.04, P=0.091);但IC+CCRT组的无远处转移生存(HR=0.56,95%CI为 0.42~0.74,P<0.001)及无进展生存期(HR=0.65,95%CI为 0.54~0.77,P<0.001)较IC+RT组提高。IC+CCRT组急性不良反应较IC+RT组明显增加。结论 鼻咽癌治疗中两种治疗模式总生存相当,而IC+CCRT组的无远处转移生存及无进展生存较优于IC+RT组,但不良反应发生率也相应增加。IC+CCRT或许可作为鼻咽癌患者的一种推荐治疗方式,但需要更多研究。     

Lack of benefit of concurrent chemotherapy in patients with cervical cancer and negative lymph nodes by FDG-PET

PURPOSE: To compare the outcome of patients with cervical cancer and negative lymph nodes by fluorodeoxyglucose-positron emission tomography (FDG-PET) treated with irradiation (RT) and concurrent chemotherapy or RT alone. METHODS AND MATERIALS: This was a prospective data registry of 65 patients with cervical cancer and negative lymph nodes by whole-body FDG-PET. The tumor stage was IB2 in 11, IIB in 37, and IIIB in 17 patients. RT alone was administered to 15 and RT with concurrent weekly cisplatin to 50 patients. RESULTS: The 5-year overall survival estimate was 85% with RT and 81% with RT and concurrent chemotherapy (p = 0.91). The corresponding 5-year cause-specific survival estimates were 78% and 74% (p = 0.98). The differences in the sites of recurrence (pelvis vs. distant metastasis) were not statistically significant between the two groups (p = 0.77). A Cox proportional hazards model of survival outcome did not identify chemotherapy, overall treatment time, or radiation dose as statistically significant prognostic factors. Severe complications included one rectovaginal fistula, one rectal stricture requiring colostomy (both in the concurrent chemotherapy group), and one death from chemotherapy-related complications. CONCLUSION: Irradiation with concurrent cisplatin was not advantageous compared with RT alone in patients with negative lymph nodes on FDG-PET.     

Limited stage I and II follicular non-Hodgkin's lymphoma: the Nebraska Lymphoma Study Group experience

The purpose of this study was to evaluate the outcome and prognostic factors of patients with limited stage follicular non-Hodgkin's lymphoma treated prospectively by the Nebraska Lymphoma Study Group (NLSG). Forty previously untreated patients, median age 64 years, with limited stage follicular lymphoma were prospectively treated according to the protocols of the NLSG between January 1980 and December 1990. The follicular large cell type represents 75% of the cases, and 14 of the biopsies also had a diffuse component (composite lymphoma). The initial treatment was radiation therapy (RT) to the involved field in 15 patients, anthracycline-containing combination chemotherapy (CT) in 20, and combined RT and CT in 5. Thirty-seven patients (92.5%) achieved a complete remission (CR). The median follow-up is 120 months (range, 20 to 214). Of the 37 patients achieving a CR, 7 patients are alive in first CR, one died due to sepsis, another because of a myeloproliferative disorder at 77 months following chemotherapy, 6 died because of unrelated causes in first CR. Twenty-two patients relapsed between 1 to 128 months following a CR. The estimated 10-year event-free survival is 21% (95% CI: 7 to 35). Two patients received no or palliative therapy after relapse and both died of progressive disease. Nineteen patients received salvage therapy and 15 achieved a second remission. The median survival after first relapse is 55 months. The estimated 10-year overall survival is 44% (95% CI: 28 to 60). Various factors including sex, histologic subtype, stage, and degree of follicularity do not influence the overall survival or event-free survival. CT with or without RT resulted in a better trend for 10-year event-free survival in stage IA patients compared to RT alone but estimated 10-year overall survival is no different. The overall survival is worse in the > or = 60 age group but this difference is not evident if data is adjusted for cause specific death. In conclusion, limited stage follicular lymphoma has an excellent initial response to radiation therapy or chemotherapy; however the recurrence rate is high and cure is limited.     

Preliminary results of a prospective randomized trial comparing concurrent chemoradiotherapy plus adjuvant chemotherapy with radiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma in endemic regions of china

PURPOSE: A prospective randomized trial was performed to evaluate the efficacy of concurrent chemotherapy and adjuvant chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) in endemic regions of China. METHODS AND MATERIALS: Between July 2002 and September 2005, 316 eligible patients were randomly assigned to receive either radiotherapy alone (RT) or chemoradiotherapy concurrent with adjuvant chemotherapy (CRT). All patients received 70 Gy in 7 weeks using standard RT portals and techniques. The CRT patients were given concurrent cisplatin (40 mg/m(2) on Day 1) weekly during RT, followed by cisplatin (80 mg/m(2) on Day 1) and fluorouracil (800 mg/m(2) on Days 1-5) every 4 weeks (Weeks 5, 9, and 13) for three cycles after completion of RT. All patients were analyzed by intent-to-treat analysis. RESULTS: The two groups were well-balanced in all prognostic factors and RT parameters. The CRT group experienced significantly more acute toxicity (62.6% vs. 32%, p = 0.000). A total of 107 patients (68%) and 97 patients (61%) completed all cycles of concurrent chemotherapy and adjuvant chemotherapy, with a median follow-up time of 29 months. The 2-year overall survival rate, failure-free survival rate, distant failure-free survival rate, and locoregional failure-free survival rate for the CRT and RT groups were 89.8% vs. 79.7% (p = 0.003), 84.6% vs. 72.5% (p = 0.001), 86.5% vs. 78.7% (p = 0.024), and 98.0% vs. 91.9% (p = 0.007), respectively. CONCLUSIONS: This trial demonstrated the significant survival benefits of concurrent chemotherapy plus adjuvant chemotherapy in patients with locoregionally advanced NPC in endemic regions of China.     

Impact of chest wall and lung invasion on outcome of stage I-II Hodgkin's lymphoma after combined modality therapy

PURPOSE: To examine the impact of extranodal chest wall and lung invasion on the prognosis of patients with clinical Stage I-II Hodgkin's lymphoma treated with combined modality therapy. MATERIALS AND METHODS: The outcome of 324 patients with clinical Stage I-II Hodgkin's lymphoma treated with combined modality therapy between 1981 and 1996 was analyzed. Twenty-two patients had chest wall invasion and 40 had invasion of lung parenchyma. The chemotherapy regimens used were ABVD in 182 patients (56%), MOPP/ABV(D) in 45 (14%), MOPP in 86 (27%), and other chemotherapy regimens in 11 patients (3%). This was followed by mantle/mediastinal radiotherapy (RT) in 163 patients (50%), extended-field RT in 135 patients (42%), and infradiaphragmatic RT in 26 patients (8%). The impact of chest wall and lung invasion on local relapse, disease-free survival, cause-specific survival, and overall survival was examined. RESULTS: After a median follow-up of 8.3 years, the 5-year cause-specific and overall survival rate of the entire cohort was 93% and 90%, respectively. Compared with patients with no extranodal involvement, patients with chest wall invasion had significantly worse local control (89% vs. 68%, p = 0.005), disease-free survival (84% vs. 59%, p = 0.016), and cause-specific survival (94% vs. 86%, p = 0.009). Overall survival was also worse among patients with chest wall invasion, but not significantly so (90% vs. 82%, p = 0.10). Among the 16 patients with chest wall invasion but without lung invasion, 7 progressed during treatment or relapsed, 6 with local failure (crude relapse rate 44%, 95% confidence interval [CI] 19-68%), and 5 died (crude death rate 31%, 95% CI 9-54%). After adjusting for other significant prognostic factors, patients with chest wall invasion had significantly worse local control (hazard ratio 2.8, 95% CI 1.2-6.3), disease-free survival (hazard ratio 2.3, 95% CI 1.1-4.8), and cause-specific survival (hazard ratio 2.8, 95% CI 1.1-6.8). Lung invasion was not significantly associated with any of the outcomes assessed. CONCLUSIONS: Chest wall invasion is an adverse prognostic factor among clinical Stage I-II Hodgkin's lymphoma patients treated with combined modality therapy, although we did not find a worse outcome for patients with lung invasion. Efforts to reduce treatment intensity in these patients should be undertaken with caution, recognizing their increased risk of local relapse.     

Identifying breast cancer patients most likely to benefit from aromatase inhibitor therapy after adjuvant radiation and tamoxifen

BACKGROUND: The purpose of the current study was to examine patient selection for an aromatase inhibitor in breast cancer patients who were free from adverse events 5 years after treatment with tamoxifen. METHODS: In all, 471 women were treated with breast-conserving surgery, axillary lymph node dissection, and radiation. Eligibility included T1-2 disease, tamoxifen use, follow-up of >/=5 years, no prior breast cancer, and freedom from all events at 5 years of follow-up. Patients treated with chemotherapy more often had T2 disease and positive lymph nodes, and were aged <60 years compared with patients treated with tamoxifen alone. No patient during the period of the current study (1982-1999) received an aromatase inhibitor. The median follow-up was 8.25 years. RESULTS: There were 36 events: 10 contralateral breast cancers (CBCs) and 26 recurrences (8 local, 1 regional, and 17 distant). The 10-year risk of locoregional recurrence was 2.5%, the 10-year risk of CBC was 3.6%, and the 10-year risk of distant metastasis was 4.4%. The event-free survival rate for all patients was 93%. Only >/=4 positive lymph nodes and premenopausal status were found to be independent variables for decreased event-free survival on multivariate analysis. The overall survival rate was 89%. Only younger age and lower lymph node status were found to be significant predictors of improved overall survival. CONCLUSIONS: In the current study, a 40% reduction in recurrence/CBC with the addition of an aromatase inhibitor after 5 years of tamoxifen treatment would have had a marginal benefit of 1% to 2%. Women who were premenopausal and patients with >/=4 positive lymph nodes would have the greatest absolute benefit of >3% in the 10-year event-free survival rate from extended therapy. The decision needs to be individualized for patients aged >/=60 years based on their initial lymph node status and the presence of comorbidities that could lower their 5-year life expectancy.     

Central neurocytoma: management recommendations based on a 35-year experience

PURPOSE: To examine the outcomes of patients with histologically confirmed central neurocytomas. METHODS AND MATErials: The data from 45 patients with central neurocytomas diagnosed between 1971 and 2003 were retrospectively evaluated. Various combinations of surgery, radiotherapy (RT), and chemotherapy had been used for treatment. RESULTS: The median follow-up was 10.0 years. The 10-year overall survival and local control rate was 83% and 60%, respectively. Patients whose tumor had a mitotic index of <3 (per 10 high-power fields) experienced a 10-year survival and local control rate of 89% and 74%, respectively, compared with 57% (p = 0.040) and 46% (p = 0.14) for patients with a tumor mitotic index of > or =3. The 10-year survival and local control rate was 90% and 74% for patients with typical tumors compared with 63% (p = 0.055) and 46% (p = 0.41) for those with atypical tumors. A comparison of gross total resection with subtotal resection showed no significant difference in survival or local control. Postoperative RT improved local control at 10 years (75% with RT vs. 51% without RT, p = 0.045); however, this did not translate into a survival benefit. No 1p19q deletions were found in the 19 tumors tested. CONCLUSION: Although the overall prognosis is quite favorable, one-third of patients experienced tumor recurrence or progression at 10 years, regardless of the extent of the initial resection. Postoperative RT significantly improved local control but not survival, most likely because of the effectiveness of salvage RT. For incompletely resected atypical tumors and/or those with a high mitotic index, consideration should be given to adjuvant RT because of the more aggressive nature.