Long-term survival of nasopharyngeal carcinoma following concomitant radiotherapy and chemotherapy

Purpose: The purpose of this study is to demonstrate long-term survival of nasopharyngeal carcinoma treated with concomitant chemotherapy and radiotherapy (CCRT) followed by adjuvant chemotherapy.

Methods and Patients: One hundred and seven patients with Stage III and IV (American Joint Committee on Cancer, AJCC, 1988) nasopharyngeal carcinoma (NPC) were treated with concomitant chemotherapy and radiotherapy (CCRT) followed by adjuvant chemotherapy between April 1990 and December 1997 in Koo Foundation Sun Yat-Sen Cancer Center, Taipei. The dose of radiation was 70 Gray (Gy) given in 35 fractions, 5 fractions per week. Two courses of chemotherapy, consisting of cisplatin and 5-fluorouracil, were delivered simultaneously with radiotherapy in Weeks 1 and 6 and two additional monthly courses were given after radiotherapy. According to the AJCC 1997 staging system, 32 patients had Stage II disease, 44 had Stage III, and 31 had Stage IV disease.

Results: With median follow-up of 44 months, the 5-year overall survival rate in all 107 patients was 84.1%, disease-free survival rate was 74.4%, and locoregional control rate was 89.8%. The 3-year overall survival for Stage II was 100%, for Stage III it was 92.8%, and for Stage IV, 69.4% (p = 0.0002). The 3-year disease-free survival for Stage II was 96.9%, for Stage III it was 87.7%, and for Stage IV it was 51.9% (p = 0.0001).

Conclusion: CCRT and adjuvant chemotherapy is effective in Taiwanese patients with advanced NPC. The prognosis of AJCC 1997 Stage II and III disease is excellent, but, for Stage IV (M0), it is relatively poor. Future strategies of therapy should focus on high-risk AJCC 1997 Stage IV (M0) cohort.     

Role of chemoradiotherapy in intermediate prognosis nasopharyngeal carcinoma

To evaluate the long term impact of concurrent chemoradiotherapy (CCRT) compared to radiotherapy (RT) alone in patients with T2N1M0 nasopharyngeal carcinoma (NPC) retrospectively. Three hundred and ninety-two patients with T2N1M0 NPC according to the AJCC 2002 stage classification system were analyzed. Among them, 211 patients were treated with RT alone and the rest of 181 patients were treated with CCRT. A planned dose of 70 Gy was delivered in 2.0 Gy per fraction over 7 weeks to the primary tumor with 6-MV photons or (60)Cobalt γ-ray. The chemotherapy regimen of cisplatin with a dose of 100mg/m(2) was delivered for 2-3 cycles. With a median follow-up of 66 months (range 2.4-117.1 months), the 5-year overall survival (OS) and disease-free survival (DFS) rates was higher in CCRT group compared to RT alone group, though they failed to reach statistical significance (80.2% vs. 76.6%, P=0.778 and 70.5% vs. 64.2%, P=0.413, respectively). A significant improvement was detected in 5-year relapse-free survival (RFS) rate in CCRT group than RT alone group (91.5% vs. 77.3%, P=0.008). Moreover, chemotherapy was the only independent prognostic factor for the 5-year RFS (P=0.007). Concurrent chemoradiotherapy appeared to improve the 5-year RFS rate for patients with T2N1M0 NPC. Large prospective, randomized clinical studies are needed to confirm its therapeutic gain.     

Retrospective analysis of postoperative radiotherapy for node-negative cervical carcinoma with stage IB-IIB disease

BACKGROUND: We performed retrospective analysis to evaluate the outcomes of postoperative radiotherapy for patients with cervical carcinoma without lymph node metastasis. METHODS: From 1981 to 1995, 68 stage I-II cervical carcinoma patients without nodal disease who received adjuvant pelvic radiotherapy were entered into the present analysis. Criteria for postoperative radiotherapy were (1) deep stromal invasion (> or = 1/2; n = 63), (2) positive parametrial invasion (n = 38) and (3) close or positive surgical margin (n = 21). The median patient age was 54.0 years (range, 29-69 years). The median dose of 45.3 Gy (range, 43.4-56.4 Gy) was delivered over the whole pelvis median 21.0 days (range 12-68 days) after surgery. RESULTS: The 5/10-year overall survival, disease-free survival, pelvic control and distant metastasis-free survival rates were 89.7/85.7, 85.3/83.2, 95.5/95.5 and 90.7/90.7%, respectively. Histology of adenocarcinoma (n = 4), large tumor size and prolonged period between operation and radiotherapy were significantly adverse prognostic factors of overall and disease-free survival by univariate analysis. The risk score referred from the GOG report correlated well with disease-free survival (P = 0.018), but showed only a tendency for overall survival as a prognostic factor (P = 0.07). Overall treatment time proved to be a significant variable for overall survival (P = 0.02), but not for disease-free survival (P = 0.056). Both risk score and overall treatment time proved to be significant prognostic factors in the multivariate model. Major adverse effects occurred in three patients (4.4%) without mortality. CONCLUSIONS: In this analysis, clinical outcome from adjuvant postoperative radiotherapy was thought to be feasible with both satisfactory pelvic control and acceptable lower toxicity.     

Phase III study comparing standard radiotherapy with or without weekly oxaliplatin in treatment of locoregionally advanced nasopharyngeal carcinoma: preliminary results.

PURPOSE: A prospective, randomized, phase III study was performed to evaluate the feasibility and efficacy of concurrent weekly oxaliplatin with radiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: From January 2001 to January 2003, 115 patients with locoregionally advanced NPC were randomly assigned to either radiotherapy (RT) alone (56 patients) or concurrent chemoradiotherapy (CCRT; 59 patients). All patient characteristics were well balanced in both arms. CCRT with oxaliplatin 70 mg/m2 weekly was administered for six doses from the first day of RT. RESULTS: All patients were eligible for toxicity and response analysis. Compliance with the protocol treatment was excellent, with 97% of patients completing all planned doses of oxaliplatin, and a lack of high-grade toxicity was observed. After a median follow-up time of 24 months, there was a significant difference in overall survival (OS), relapse-free survival (RFS), and metastasis-free survival (MFS) in favor of the CCRT arm. The 2-year OS rates were 100% for the CCRT arm and 77% for the RT arm (P = .01). The 2-year MFS rates were 92% for the CCRT arm and 80% for the RT arm (P = .02). The 2-year RFS rates were 96% for the CCRT arm and 83% for the RT arm (P = .02). CONCLUSION: CCRT with weekly oxaliplatin is feasible and improves OS, MFS, and RFS rates in patients with locoregionally advanced NPC. Therefore, further randomized trials including oxaliplatin are warranted.     

Prognostic features and treatment outcome in locoregionally advanced nasopharyngeal carcinoma following concurrent chemotherapy and radiotherapy

Purpose: Concurrent chemotherapy and radiotherapy (CCRT) are effective in treatment of locoregionally advanced nasopharyngeal carcinoma (NPC). However, the prognostic factors after CCRT have not been evaluated. We therefore attempt to evaluate factors that influence treatment outcomes following CCRT.Methods and Materials: Seventy-four (5 in stage III and 69 in stage IV) patients with locoregionally advanced NPC were treated with CCRT. Radiotherapy was delivered either at 2 Gray (Gy) per fraction per day up to 70 Gy or 1.2 Gy, 2 fractions per day, up to 74.4 Gy. Concurrent chemotherapy consisted of cisplatin and 5-fluorouracil. Cox proportional-hazards model was used to analyze the prognostic factors which included age, gender, pathologic type, T, N, lactate dehydrogenase (LDH), and infiltration of the clivus.Results: The primary tumor control rate at 3 years was 96.7% (95% confidence interval [CI]: 92.5–100), distant metastasis–free survival 81.1% (95% CI: 70.6–91.6), disease-free survival 77.0% (95% CI: 65.3–88.7), and overall survival 79.8% (95% CI: 69.2–90.4) with a median follow-up interval of 29 months (range 15–74 months). Cox proportional-hazards model revealed that infiltration of the clivus and serum level of LDH before treatment were the most two important factors that predict distant metastases. Infiltration of the clivus and the serum LDH level greater than 410 U/L were strongly associated with distant metastasis–free survival (p = 0.0004 and p = 0.0002, respectively). When these two risk factors were considered together, no distant metastasis was observed in 40 patients with both intact clivus and LDH ≦410 U/L. On the contrary, 13 of the remaining 34 patients with at least one risk factor developed distant metastasis (p = 0.0001).Conclusion: Our study demonstrates that CCRT can improve the primary tumor control of 96.7% and disease-free survival of 77.0% at 3-year follow-up. Distant metastasis, however, is the major cause of failure. Infiltration of the clivus by the tumor and LDH greater than 410 U/L are the two independent and useful prognostic factors in patients with locoregionally advanced NPC who were treated with CCRT. Good- and poor-risk patients can be distinguished by virtue of their having both conditions.     

Concomitant radiotherapy and chemotherapy for early-stage nasopharyngeal carcinoma.

PURPOSE: Early-stage nasopharyngeal carcinoma (NPC) continues to carry a failure rate of 15% to 30% when treated with radiotherapy alone; the benefit of concomitant radiotherapy and chemotherapy (CCRT) in early-stage NPC is unclear. The purpose of this report is to describe our efforts to improve treatment outcome in early-stage NPC after CCRT. PATIENTS AND METHODS: Of 189 newly diagnosed NPC patients without evidence of distant metastases who were treated in our institution between 1990 and 1997, 44 presented with early-stage (stage I and II) disease according to the American Joint Committee on Cancer (AJCC) 1997 NPC staging system. Twelve of these patients were treated with radiotherapy alone and 32 with CCRT. Each patient's head and neck area was evaluated by magnetic resonance imaging or computed tomography. Radiotherapy was administered at 2 Gy per fraction per day, Monday through Friday, for 35 fractions for a total dose of 70 Gy. Chemotherapy consisting of cis-diamine-dichloroplatinum and fluorouracil was delivered simultaneously with radiotherapy in weeks 1 and 6 and sequentially for two monthly cycles after radiotherapy. RESULTS: Patients who were treated with radiotherapy alone primarily had stage I disease, whereas none of those who were treated with CCRT had stage I disease (11 of 12 patients v none of 32 patients; P =.001). The locoregional control rate at 3 years for the radiotherapy group was 91.7% (median follow-up period, 34 months) and was 100% for the CCRT group (median follow-up period, 44 months) (P =.10). The 3-year disease-free survival rate in the radiotherapy group was 91.7% and was 96.9% in the CCRT group (P =.66). CONCLUSION: Our results reveal excellent prognosis of AJCC 1997 stage II NPC treated with CCRT. Stage II patients with a greater tumor burden treated with CCRT showed an equal disease-free survival, compared with stage I patients treated with radiotherapy alone. A prospective randomized trial is underway to confirm the role of CCRT in stage II NPC.     

调强放疗结合诱导化疗或同期加辅助化疗治疗局部晚期鼻咽癌的疗效比较

目的:比较诱导化疗加调强放疗和同期放化疗加辅助化疗治疗局部晚期鼻咽癌的疗效。方法:收集2004年1 月至2008年12月中山大学肿瘤医院收治的经病理证实的局部晚期鼻咽癌240 例,其中采用顺铂+ 5-FU 诱导化疗加调强放疗（诱导组）117 例,采用顺铂、调强放疗同期放化疗加顺铂+ 5-FU 辅助化疗（同期组）123 例。应用Kaplan-Meier 和Log-rank 法计算和比较两组患者的生存率。结果:诱导组和同期组的5 年总生存率、无瘤生存率、无转移生存率、无鼻咽复发生存率和无颈部复发生存率分别为78.0% 和78.7% 、68.9% 和67.5% 、79.0% 和77.0% 、91.6% 和91.0% 、95.3% 和93.7% ,两组比较差异无统计学意义（P>0.05）。 同期组Ⅲ、Ⅳ级恶心呕吐和白细胞减少的发生率明显高于诱导组。多因素分析结果显示N 分期和年龄是影响局部晚期鼻咽癌患者总生存的预后独立因素。结论:诱导化疗加调强放疗治疗局部晚期鼻咽癌的疗效达到同期放化疗加辅助化疗的水平,远处转移是局部晚期鼻咽癌治疗失败的主要原因。      

Anemia in cervical cancers: impact on survival,patterns of relapse,and association with hypoxia and angiogenesis

PURPOSE: The prognostic impact of anemia in cervical cancers is well established. We have investigated the impact of anemia on prognosis and patterns of relapse in cervical cancers. Furthermore, we analyzed the relationship between anemia, tumor hypoxia, and angiogenesis. METHODS AND MATERIALS: Eighty-seven patients (mean age 58 years) with squamous cell cancer of the cervix (Stage IIB: n = 19; Stage IIIB: n = 59; Stage IVA: n = 9) were prospectively enrolled in the study from 1995 through 1999. Patients underwent definitive radiotherapy with a combination of external beam radiotherapy (45-50.4 Gy) and high-dose-rate brachytherapy (5 x 7 Gy). Tumor oxygenation was measured with the Eppendorf pO(2)-histograph before radiotherapy and after 19.8 Gy. Angiogenesis was determined by measuring the microvessel density in pretreatment biopsies in 46 patients. The impact of tumor oxygenation (at 0 Gy and 19.8 Gy), hemoglobin (hb) level (at 0 Gy and 19.8 Gy), angiogenesis and clinical parameters on survival and relapse was investigated. RESULTS: The 3-year overall survival rate (after a median follow-up of 42 months) was 57% for the whole group of patients, 72% for Stage IIB, 60% for Stage IIIB, and 22% for Stage IVA. The presence of pretreatment anemia had a significant impact on the relapse rate. However, the midtherapy hb level (at 19.8 Gy) had the strongest impact on local failure rate and survival: 3-year local failure rate was 6% in 20 patients with a hb > 13 g/dL at 19.8 Gy, 15% in 47 patients with an hb between 11 and 13 g/dL, and 67% in 20 patients with an hb < 11 g/dL, p = 0.0001. This was associated with a significant impact on the 3-year overall survival, 79% vs. 64% vs. 32%. Twenty-three tumors were poorly oxygenated at both measurements (oxygen pressure [median pO(2)] < 15 mm Hg before therapy and at 19.8 Gy). This group had a significantly lower 3-year overall survival as compared with patients with high pO(2) before and/or at 19.8 Gy (38% vs. 68%, p = 0.02), and these poorly oxygenated tumors had also a significantly increased microvessel density. In a multivariate model, the midtherapy hb level maintained an overwhelming impact on local failure rate and survival. CONCLUSION: Hemoglobin level during radiotherapy was the strongest prognostic factor for local control and survival. We could further identify a poor prognostic subgroup with persisting hypoxia during radiotherapy, low hb levels, and increased angiogenesis. According to these findings, an association between anemia, poor tumor oxygenation, and angiogenesis is likely.     

Impact of adjuvant therapy on survival of patients with early-stage uterine papillary serous carcinoma

PURPOSE: To determine the efficacy of adjuvant therapy in patients with early-stage uterine papillary serous carcinoma. METHODS AND MATERIALS: Data were collected on all surgically staged Stage I-II uterine papillary serous carcinoma patients. Statistical analyses were performed using the Kaplan-Meier and Cox proportional hazards regression methods. RESULTS: Of 68 patients, 50 had Stage I and 18 had Stage II disease; 35 underwent adjuvant treatment, including radiotherapy in 26, chemotherapy in 7, and combined RT and chemotherapy in 2. The remaining 33 were treated expectantly. The median follow-up was 56 months (range 1-173). The 5-year overall survival rate was 69%. Of 19 patients with disease limited to the endometrium, 10 received no additional therapy, 3 of whom developed recurrence. However, all 9 women who underwent adjuvant treatment remained free of disease. Patients receiving adjuvant therapy with chemotherapy or radiotherapy had a prolonged 5-year overall and disease-free survival compared with those who were treated expectantly (85% vs. 54%, p = 0.002 for overall survival and 85% vs. 49%, p = 0.01 for disease-free survival). In multivariate analysis, adjuvant therapy (p = 0.035) and the absence of lymphovascular space invasion (p = 0.001) remained as independent prognostic factors for improved survival. CONCLUSION: Adjuvant therapy with chemotherapy or radiotherapy improves the survival of women with early-stage uterine papillary serous carcinoma.     

Examining prognostic factors and patterns of failure in nasopharyngeal carcinoma following concomitant radiotherapy and chemotherapy: impact on future clinical trials

PURPOSE: Concomitant chemotherapy and radiotherapy (CCRT), followed by adjuvant chemotherapy, has improved the outcome of nasopharyngeal carcinoma (NPC). However, the prognosis and patterns of failure after this combined-modality treatment are not yet clear. In this report, the prognostic factors and failure patterns we observed with CCRT may shed new light in the design of future trials. METHODS AND PATIENTS: One hundred forty-nine (149) patients with newly diagnosed and histologically proven NPC were prospectively treated with CCRT followed by adjuvant chemotherapy between April 1990 and December 1997. One hundred and thirty-three (89.3%) patients had MRI of head and neck for primary evaluation before treatment. Radiotherapy was delivered either at 2 Gy per fraction per day up to 70 Gy or 1.2 Gy per fraction, 2 fractions per day, up to 74.4 Gy. Chemotherapy consisted of cisplatin and 5-fluorouracil. According to the AJCC 1997 staging system, 32 patients were in Stage II, 53 in Stage III, and 64 in Stage IV (M0). RESULTS: Univariate analysis revealed that WHO (World Health Organization) Type II histology, T4 classification, and parapharyngeal extension were poor prognostic factors for locoregional control. Multivariate analysis revealed that T4 disease was the most important adverse factor that affects locoregional control, the risk ratio being 5.965 (p = 0.02). Univariate analysis for distant metastasis revealed that T4 and N3 classifications, serum LDH level > 410 U/L (normal range, 180-460), parapharyngeal extension, and infiltration of the clivus were significantly associated with poor prognosis. Multivariate analysis, however, revealed that T4 classification and N3 category were the only two factors that predicted distant metastasis; the risk ratios were 3.994 (p = 0.02) and 3.390 (p = 0.01), respectively. Therefore, based on the risk factor analysis, we were able to identify low-, intermediate-, and high-risk patients. Low-risk patients were those without the risk factors mentioned above. They consisted of Stage II patients with T2aN0, T1N1, and T2aN1 categories and of Stage III patients with T1N2 and T2aN2 categories. Their risk of recurrence is low (4%). Intermediate-risk patients were those with at least one univariate risk factor. They are Stage II patients with T2bN0 and T2bN1 categories and Stage III patients with T2bN2 and T3N0-2 categories. The risk of recurrence is modest (18%). High-risk patients have risk factors by multivariate analysis. They are stage T4 or N3 patients. Their risk of recurrence is high (36%). CONCLUSION: Low-risk patients have an excellent outcome. Future trials should focus on reducing treatment-associated toxicities and complications and reevaluate the benefit of sequential adjuvant chemotherapy. The recurrence in treatment of intermediate-risk patients is modest; CCRT and adjuvant chemotherapy may be the best standard for them. Patients with T4 and N3 disease have poorer prognosis. Hyperfractionated radiotherapy may be considered for the T4 patients. Future study in these high-risk patients should also address the problem of distant spread of the disease.     

Single institute experience of chemotherapy and adjuvant radiotherapy for localized aggressive non-Hodgkin's lymphoma: retrospective analysis of the clinical efficacy of radiation therapy

We retrospectively analyzed the clinical outcome of localized aggressive lymphoma treated with chemotherapy and adjuvant radiotherapy. Between 1982 and 1998, 77 patients who were diagnosed as having aggressive lymphoma stage I-II were treated with chemotherapy followed by radiation therapy. The median radiation dose was 44.4 Gy (range, 30-64 Gy). Some patients who achieved complete response after chemotherapy received limited-field radiation to reduce toxicity. Several prognostic factors were analyzed in the overall (OAS) and relapse-free survival (RFS) by both uni- and multivariate analysis. The 5-year rates of OAS and RFS were 74.6% and 70.8%, respectively. Patient age (p = 0.016), radiation dose (p = 0.043), and prognostic score proposed by the Japan Lymphoma Radiation Therapy Group (JLRTG; p = 0.0073) were significant predictive factors for OAS. As for RFS, predictive factors were patient age (p = 0.042), elevated level of serum lactic dehydrogenase (p = 0.046), and JLRTG score (p = 0.05). At the multivariate level, only patient age greater than 60 years was a significantly adverse variable for both OAS (p = 0.0079) and RFS (p = 0.0198). Our treatment strategy was thought to be acceptable with satisfactory outcomes. Limited-field radiation may have possible advantages in toxicity if it does not lead to worsening of the outcome, although a conclusive result could not be obtained by the current analysis.     

Ⅳ期非小细胞肺癌287例放疗后的生存分析

背景与目的:很多Ⅳ期非小细胞肺癌(non-smallcelllungcancer,NSCLC)的患者需要放疗,特别是对脑、骨转移者放疗有很好的治疗作用。本研究旨在分析放疗对Ⅳ期NSCLC患者生存的影响。方法:对287例资料完整的Ⅳ期NSCLC放疗患者进行回顾性分析。脑放疗为平行对穿两野全脑照射,骨放疗为单野局部照射,对原发灶、区域淋巴结和其它转移部位用2维常规分割或3维适形放疗(3dimensionalconformalradiotherapy,3D-CRT)。脑和骨放疗通常采用4周20次共40Gy或2周10次共30Gy的治疗方案,原发灶和区域淋巴结的中位照射剂量是50Gy(20～70Gy),其它转移部位的中位照射剂量是46Gy(40～60Gy)。结果:全部患者中位生存期9个月(8～10个月),1年和2年生存率分别是30.2%和8.9%。有化疗和无化疗者中位生存期分别为10个月和8个月(P=0.049)。有脑转移、骨转移、其它转移者中位生存期分别为8个月、9个月、10个月,1年生存率分别24.8%、28.7%和37.5%,2年生存率分别为6.7%、7.0%和15.3%。单因素分析发现对生存有显著影响的因素为病理类型和年龄。腺癌患者的生存期高于鳞癌和其它病理类型,中位生存期分别为10个月、7个月、9个月(P=0.046);≤60岁的患者生存期显著高于>60岁的患者,中位生存期分别为11月、8个月(P=0.012);单纯骨转移患者的中位生存期要大于合并有其它转移者(10个月与6个月,P=0.033),而单纯脑转移和同时合并有其它转移的两组患者中位生存期却无明显差异(9个月与8个月,P=0.3742);肿瘤原发灶和区域淋巴结是否放疗对患者生存时间影响不大(10个月与8个月,P=0.066);是否伴有其它慢性疾病对患者的生存期无明显影响(9个月与10个月,P=0.306)。对脑和骨转移的患者采用4周20次40Gy或2周10次30Gy放疗对生存期无明显影响。结论:病理类型、年龄对Ⅳ期NSCLC患者的放疗疗效有显著影响,全脑和骨转移采用4周20次40Gy或2周10次30Gy放疗对生存期无明显影响。     

Primary glioblastoma multiforme in younger patients: a single-institution experience

AIMS AND BACKGROUND: To report our experience of patients with primary glioblastoma multiforme of young age by evaluating the characteristics, prognostic factors, and treatment outcomes. PATIENTS AND METHODS: Seventy patients with primary glioblastoma multiforme (GBM) treated at our department between 1996 and 2004 were studied. The male-female ratio was 2.6:1. The median age was 53 (16-74). Sixty-eight patients (97%) were operated on before radiotherapy and 2 patients (3%) underwent only stereotactic biopsy. All patients received radiotherapy. Postoperative chemotherapy as an adjuvant to radiotherapy was given to 9 patients (12%). The patients were divided into 2 groups according to their age (group A < or = 35 years, n = 21 vs group B > 35 years, n = 49). Survival was determined with the Kaplan-Meier method and differences were compared using the log-rank test. Cox regression analysis was performed to identify the independent prognostic factors. Karnofsky performance status (> or = 70 vs < 70), age (< or = 35 vs > 35 years), gender, tumor size (< or = 4 vs > 4 cm), number of involved brain lobes (1 vs more than 1), type of surgery (total vs subtotal), preoperative seizure history (present vs absent), radiotherapy field (total cranium vs partial), total radiotherapy dose (60 vs 66 Gy), and adjuvant chemotherapy (present vs absent) were evaluated in univariate analysis. RESULTS: The median survival was 10.3 months in the whole group, 19.5 months in the younger age group and 5.7 months in the older age group. During follow-up re-craniotomy was performed in 2 patients (3%), and 1 patient (1%) developed spinal seeding metastases and was given spinal radiotherapy. In univariate analysis younger age vs older age: median 19.5 months vs 5.27 months (P = 0.0012); Karnofsky performance status > or = 70 vs < 70: median 15.3 months vs 2.67 months (P < 0.0001), and external radiotherapy dose 60 Gy vs 66 Gy: median 11.6 months vs 3 months (P = 0.02) were found as significant prognostic factors for survival. In regression analysis a worse performance status (KPS <70) was found to be the only independent factor for survival (P = 0.014, 95% CI HR = 0.0043 [0.0001-0.15]). CONCLUSIONS: Younger patients with primary glioblastoma multiforme had a relatively long survival (median, 19.5 months, with a 2-year survival rate of 30%) compared to older patients. This was due particularly to their better performance status.     

Intraoral adenoid cystic carcinoma: prognostic factors and outcome

Intraoral (oral cavity and oropharynx) adenoid cystic carcinomas are uncommon cancers characterized by slow evolution, protracted clinical course, multiple and/or delayed recurrences, and late distant metastases. The molecular biology behind this enigmatic disease remains poorly characterized. To analyze and correlate prognostic factors with outcome in intraoral adenoid cystic carcinoma. Medical records of 76 patients with intraoral adenoid cystic carcinoma treated with definitive loco-regional therapy at the institute between 1992 and 2004 were retrospectively reviewed and analyzed.Majority (85.5%) of the patients had advanced stage disease. Seventy-four patients underwent surgery, of which 51 (68.9%) received adjuvant radiotherapy. The median dose of radiation was 56 Gy (range 44-66 Gy). Two patients with medical co-morbidities received radical radiotherapy. Perineural invasion, margin positivity and nodal positivity were present in 24 (32.4%); 27 (36.4%); and 15 (19.7%) patients, respectively. Ten (13.1%) patients developed local recurrence and 6 (7.8%) distant metastases. With a median follow-up of 20 months (range 1-137 months), the 5-year Kaplan-Meier estimates of local control and disease-free survival were 57.9% and 47.1%, respectively. On uni-variate analysis, perineural invasion (p=0.003), oropharyngeal primary (p=0.033), and advanced T-stage (p=0.047) were associated with increased local recurrences. Perineural invasion (p=0.05) and primary site (p=0.042) also predicted disease-free survival. On multivariate analysis, both perineural invasion and primary site retained significance for local control (p=0.007, p=0.011) and disease-free survival (p=0.018, p=0.014), respectively. Intraoral adenoid cystic carcinoma is an uncommon disease with an enigmatic clinical course. Perineural invasion, site of primary, and T-stage significantly impact upon local control and disease-free survival. The role of adjuvant radiotherapy remains controversial. Larger prospective studies with mature follow-up are needed to define the optimal treatment of intraoral adenoid cystic carcinoma.     

An association between preoperative anemia and decreased survival in early-stage non-small-cell lung cancer patients treated with surgery alone

PURPOSE: Surgical resection is the mainstay of therapy for patients presenting with Stage I and II non-small-cell lung cancer (NSCLC). Despite optimal staging and surgery, these patients are still at significant risk for failure. The purpose of this study is to report a retrospective analysis of the outcome of patients treated with surgery alone, as well as to analyze prognostic factors associated with survival. MATERIALS AND METHODS: From May 2000 to November 2002, there was a total of 125 patients who were treated with surgery for NSCLC at University of Maryland Medical Center. Of these, 82 Stage I and II patients who received surgery alone as the definitive therapy were identified. The median age of the entire cohort was 68 years (range, 43-88 years). There were 48 males and 34 females. Sixty-three patients (76.8%) underwent lobectomies whereas 19 patients (23.2%) underwent nonlobectomy (wedge resection or segmentectomy) procedures. Patients who received neoadjuvant or adjuvant radiation therapy or chemotherapy were excluded from the study. Factors included in univariate and multivariate analyses were age, sex, tumor histology, pathologic stage, p53 status, preoperative hemoglobin (Hgb), and type of surgery performed. Endpoints of the study were relapse-free survival (RFS) and overall survival (OS). RESULTS: Median follow-up was 20.8 months (range, 0.4-43.2 months). For the entire cohort, the 2-year RFS was 66.0% and 2-year OS was 76.3%. Median survival for the entire cohort has not been achieved. In univariate analysis, the only factor that achieved statistical significance was preoperative Hgb level. Patients who had preoperative Hgb <12 mg/dL experienced significantly worse RFS (mean RFS: 26.6 months vs. 34.9 months, p = 0.043) and OS (median OS: 27 months vs. 42.5 months, p = 0.011). For Stage I patients (n = 72), the 2-year RFS and OS were 66.4% and 77.1%, respectively. In the subgroup of stage IA patients (n = 37), there was a trend toward decreased overall survival in the anemic patients (2-year OS of 65.6% vs. 90.9%, p = 0.07). For Stage II patients (n = 10), the 2-year RFS and OS were 60.0% and 66.7%. In the Cox multivariate regression analysis, the only factor that achieved statistical significance was preoperative Hgb, with patients with Hgb <12 mg/dL having decreased RFS (RR 4.1, p = 0.020) and OS (RR 2.9, p = 0.026). There was a trend toward worse RFS (p = 0.056) and OS (p = 0.068) in p53-negative patients (n = 39). Stage, histologic type, type of surgery performed, age, and sex did not affect outcome. CONCLUSIONS: In our cohort of mostly Stage I NSCLC patients treated with surgery only, preoperative Hgb <12 mg/dL predicted for worse outcome. This effect was observed even in the traditionally low-risk subgroup of completely resected stage IA patients. Much has been written in the literature about anemia causing possible worsening of tumor hypoxia within solid tumors, thereby increasing radio-resistance. This has been a popular argument to explain poorer outcomes of anemic patients with solid tumors who undergo radiotherapy. However, our data suggest that anemia may be a sign of a more aggressive tumor that is at an increased risk of failure independent of the treatment modality.     

Prognostic factors in localized soft-tissue sarcomas

The prognostic factors associated with local failure and overall survival and the effect of radiotherapy were determined in 77 patients with localized (extremity and nonextremity) operable soft-tissue sarcoma. There were 52 male and 25 female patients; median age was 50 years (range: 15-83). Histologic grade of the tumors was as follows: low-intermediate grade in 32 cases and high grade in 29 cases. The primary tumors were treated by marginal resection (20 patients), wide resection (52 patients), and radical resection (5 patients). Adjuvant radiotherapy was applied to 50 (65%) patients. The 5-year local recurrence-free survival rate was 70.6%. Treatment with adjuvant radiotherapy and development of metastases were the significant prognostic factors associated with local recurrence. Radiotherapy was more effective in patients with tumors 10 cm or larger, marginally resected, extremity located, and high grades. The overall survival rate was 64.4% at 5 years. Significant adverse prognostic factors were high grade tumors, presence of local recurrence, and development of metastases in univariate analyses. Development of metastases and old age were the only adverse prognostic factors by multivariate analysis. The best 5-year survival rate was obtained in female patients younger than 50 years (90%). The present study demonstrated the importance of adjuvant radiotherapy and development of metastases as prognostic factors for local control. Again, development of metastases and age were the most important prognostic factors in operable soft-tissue sarcomas.     

European Organization for Research and Treatment of Cancer and Groupe d'Etude des Lymphomes de l'Adulte very favorable and favorable, lymphocyte-predominant Hodgkin disease

BACKGROUND: Lymphocyte-predominant Hodgkin disease (LPHD) is rare and has a natural history different from that of classic Hodgkin disease. There is little information in the literature regarding the role of chemotherapy in patients with early-stage LPHD. The objective of this study was to examine recurrence free survival (RFS), overall survival (OS), and patterns of first recurrence in patients with LPHD who were treated with radiotherapy alone or with chemotherapy followed by radiotherapy. METHODS: From 1963 to 1996, 48 consecutive patients ages 16-49 years (median, 28 years) with Ann Arbor Stage I (n = 30 patients) or Stage II (n = 18 patients), very favorable (VF; n = 5 patients) or favorable (F; n = 43 patients) LPHD, according to the European Organization for Research and Treatment of Cancer and Groupe d'Etude des Lymphomes de l'Adulte (EORTC-GELA) criteria, received radiotherapy alone (n = 37 patients) or received chemotherapy followed by radiotherapy (n = 11 patients). The percentages of patients with VF disease (11% vs. 9% in the radiotherapy group vs. the chemotherapy plus radiotherapy group, respectively) or F disease (89% vs. 91%, respectively) within the two treatment groups were similar (P = 1.00). A median of three cycles of chemotherapy with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or with mitoxantrone, vincristine, vinblastine, and prednisone (NOVP) was given initially to six patients and five patients, respectively. A median total radiotherapy dose of 40 grays (Gy) given in daily fractions of 2.0 Gy was delivered to both treatment groups. RESULTS: The median follow-up was 9.3 years, and 98% of patients were observed for > or = 3.0 years. RFS was similar for patients who were treated with radiotherapy alone and patients who were treated with chemotherapy followed by radiotherapy (10-year survival rates: 77% and 68%, respectively; P = 0.89). The OS rate also was similar for the two groups (10-year survival rates: 90% and 100%, respectively; P = 0.43). MOPP or NOVP chemotherapy did not reduce the risk of recurrence outside of the radiotherapy fields. CONCLUSIONS: MOPP or NOVP chemotherapy did not improve RFS or OS significantly in patients with VF or F LPHD, although the statistical power was limited. Ongoing clinical trials will help to clarify the role of a watch-and-wait strategy or systemic therapy, including anthracycline (epirubicin or doxorubicin), bleomycin, and vinblastine-based chemotherapy or antibody-based approaches, in the treatment of these patients.     

Management of nonsinonasal neuroendocrine carcinomas of the head and neck

BACKGROUND: Nonsinonasal neuroendocrine carcinomas (NSNEC) of the head and neck are rare and pose a diagnostic and management challenge. The authors undertook a retrospective study to gain insights into the spectrum of clinicopathologic characteristics, patterns of failure, and optimal management of patients with this disease. METHODS: The authors treated 23 adults with pathologically proven, nonmetastatic, primary NSNEC from 1984 to 2001. The majority (13 patients) had laryngeal origin with the following American Joint Committee on Cancer stage distribution: Stage I disease in 1 patient, Stage II disease in 2 patients, Stage III disease in 6 patients, and Stage IV disease in 14 patients. Nine patients underwent definitive surgery with or without postoperative radiation, and 14 patients received definitive radiotherapy. The median definitive radiation dose was 66 grays (Gy) (range, 44-72 Gy) using conventional fractionation. Fourteen patients received chemotherapy, with two to four cycles of induction platinum plus etoposide used most commonly. RESULTS: The median follow-up time for surviving patients was 40 months (range, 15-89 months). The actuarial 2-year and 5-year overall survival (OS) rates were 53% and 33%, respectively; and the disease-free survival (DFS) rates were 41% and 25%, respectively. Both the 2-year OS rate (68% vs. 30%; P = 0.002) and the 2-year DFS rate (55% vs. 17%; P = 0.004) were improved with chemotherapy compared with local therapy alone. Seventy-five percent of patients with measurable disease had complete clinical responses to induction chemotherapy. There was 100% complete clinical response of tumor after radiotherapy. The actuarial 2-year local failure rate was 23%. Chemotherapy did not reduce local failure (P = 0.91). There was no regional failure. The 2-year and 5-year distant metastasis rates were 54% and 71%, respectively. The 2-year rates of metastases without and with chemotherapy were 79% and 39%, respectively (P = 0.006). The 2-year and 5-year rates of intracranial metastases were 25% and 44%, respectively, and the 2-year and 5-year rates of isolated brain metastases were 21% and 41%, respectively. CONCLUSIONS: Based on these results, the authors' treatment strategy for patients with NSNEC is sequential chemotherapy and radiation. They recommend full-dose radiotherapy alone for patients with NSNEC who achieve a complete clinical response to induction chemotherapy. Newer chemotherapeutic regimens or additional adjuvant chemotherapy should be investigated for patients with NSNEC given the high rate of distant failure. Due to the very high rate of brain metastases among patients in the current study, the authors now consider incorporating prophylactic cranial irradiation into primary radiotherapy for individual patients who have complete clinical responses to induction chemotherapy.     

Improved long-term survival with combined modality therapy for pediatric nasopharynx cancer

PURPOSE: Nasopharynx cancer is a rare malignancy in childhood. This study aims to determine the role of chemotherapy, the optimal dose of radiation, and the long-term outcome for children with locoregional disease. METHODS AND MATERIALS: Thirty-three patients [median age 14 (range: 12-20) years] were treated for Stage I-IVB nasopharynx cancer. Thirteen patients (39%) received radiotherapy alone and 20 patients (61%) had chemotherapy and radiotherapy. The median radiation dose to the primary tumor was 66 Gy (range: 54-72 Gy). The median follow-up time for surviving patients was 8.4 years (range: 0.5-23.6 years). RESUL TS: The actuarial 10-year locoregional relapse-free survival, distant metastases-free survival, and overall survival rates were 77%, 68%, and 58% , respectively. Locoregional control was improved for patients treated with radiation doses > 60 Gy compared to those receiving < or = 60 Gy (93% vs. 60%, p < 0.03). The addition of chemotherapy had no significant effect on locoregional control but did reduce the development of distant metastases (16% vs. 57%, p = 0.01). Combined modality therapy improved 10-year disease-free survival (84% vs. 35%, p < 0.01) and survival (78% vs. 33%, p < 0.05) over radiation alone. The 10-year actuarial rate of severe complications was 24%.60 Gy are used for gross disease. The addition of chemotherapy decreases the risk of distant metastases and increases survival.     

Adjuvant concurrent chemoradiotherapy with intensity-modulated pelvic radiotherapy after surgery for high-risk, early stage cervical cancer patients

PURPOSE: This study was undertaken to assess local control and toxicity with adjuvant intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy (CCRT) for early stage cervical cancer. PATIENTS AND METHODS: Between June 2004 and February 2007, 54 patients with early stage cervical cancer (stage IB-IIA) with high-risk factors for treatment failure after surgery were treated with adjuvant pelvic IMRT and CCRT. Adjuvant chemotherapy consisted of cisplatin (50 mg/m2) weekly for 4 to 6 courses. All the patients received 50.4 Gy of external beam radiotherapy with IMRT in 28 fractions and 6 Gy of high-dose rate vaginal cuff brachytherapy in 3 insertions. RESULTS: Adjuvant CCRT with IMRT provided good local tumor control in posthysterectomy cervical cancer patients with high-risk pathologic features. The 3-year locoregional control and disease-free survival were 93% and 78%, respectively. Histology and lymph node metastasis were indicators for disease-free survival. Low acute and chronic treatment-related toxicities were noted with IMRT. All the patients completed the radiotherapy treatment without any major toxicity. In terms of chronic toxicity, only 1 patient had grade 3 genitourinary toxicity and none had grade 3 gastrointestinal toxicity. CONCLUSION: Our results indicate that adjuvant CCRT with IMRT technique for adjuvant treatment of early stage cervical cancer is associated with excellent local control and low toxicity.