FDG uptake correlates with recurrence and survival after treatment of unresectable stage III non-small cell lung cancer with high-dose proton therapy and chemotherapy

ABSTRACT: BACKGROUND: We studied whether maximum standardized uptake values (SUV) from [18F] PET/CT predict clinical outcome after concurrent proton/chemotherapy for stage III non-small cell lung cancer (NSCLC). METHODS: Eighty-four patients were treated prospectively with 74 Gy(RBE) proton therapy and concurrent chemotherapy. PET/CT scans were available before (SUV1) and within 6 months after (SUV2) treatment. The predictive value of clinical and PET/CT factors were analyzed with univariate and multivariate Cox regression models. RESULTS: Median survival time was 29.9 months. At 3 years, the local recurrence-free survival (LRFS) rate was 34.8%; distant metastasis-free survival (DMFS), 35.4%; progression-free survival (PFS), 31.2%; and overall survival (OS), 37.2%. Patients with SUV2 [greater than or equal to] 3.6 (the median) had high rates of LR (p = 0.021). Of 12 clinicopathologic features evaluated in univariate analysis, only KPS, SUV1, and SUV2 predicted LRFS, DMFS, PFS, and OS (p <0.05). Multivariate analysis showed that KPS (p = 0.025) and SUV2 (p = 0.017) were independently prognostic for LRFS and that SUV1, SUV2, and KPS were independently prognostic for DMFS, PFS, and OS (p <0.05). CONCLUSIONS: SUV2 predicted LRFS, and SUV1 and SUV2 predicted DMFS, PFS, and OS, in patients with stage III NSCLC treated with concurrent chemotherapy and high-dose proton therapy.     

Equivalent outcome of patients with clinical Stage IIIA non-small-cell lung cancer treated with concurrent chemoradiation compared with induction chemotherapy followed by surgical resection

PURPOSE: To compare the outcome of induction chemotherapy followed by surgery (C/S) and concurrent chemoradiotherapy (CRT) for clinical Stage IIIA non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: Between 1990 and 2000, 107 patients underwent either induction C/S (n = 55) or concurrent CRT (n = 52) for clinical Stage IIIA NSCLC at The University of Texas M. D. Anderson Cancer Center. Patient and tumor characteristics were balanced in the two treatment groups with respect to T and N stage, race, median age, performance status, weight loss, and histologic findings. In the C/S group, induction chemotherapy included two to four cycles of cisplatin-based chemotherapy followed by lobectomy and mediastinal lymph node dissection. Postoperative RT was delivered in 35 patients, with referral for RT made at the discretion of the treating physician. CRT consisted of three cycles of cisplatin-based chemotherapy given every 3 weeks concurrent with RT to 60-63 Gy in 30-35 fractions in 27 patients and 69.6 Gy in 58 fractions (b.i.d.) in 25 patients. Local control, overall disease-free survival, and distant metastasis-free survival rates were calculated using the Kaplan-Meier method. The median follow-up duration was 20 months in all patients and 32 months in surviving patients. RESULTS: No statistically significant differences were found in the end points measured in the two treatment groups. Specifically, the median survival time was 31 and 27 months and the 5-year overall survival rate was 33% and 30% in the C/S and CRT groups, respectively. Likewise, the 5-year local control (58% vs. 61%), disease-free (24% vs. 23%), and distant metastasis-free (44% vs. 36%) survival rates in the two groups were not significantly different. In the C/S group, postoperative RT significantly improved the 5-year local control rate from 33.8% to 81.5% (p = 0.007) but did not significantly improve overall survival. Additionally, patients in the C/S group whose disease responded to induction chemotherapy had a significantly improved 5-year overall survival rate (50%) compared with those who had stable or progressive disease (16%, p = 0001). CONCLUSION: Treatment of Stage IIIA NSCLC using either induction C/S or CRT resulted in similar outcomes in terms of local control and median overall, 5-year overall, distant metastasis-free, and disease-free survival. However, patients undergoing induction C/S often needed postoperative RT to achieve local control equivalent to that achieved with concurrent CRT. Advances in radiation-based treatment as reflected in this study have resulted in similar outcomes compared with modern induction C/S. To improve survival, however, newer systemic agents that reduce and control distant metastasis are required.     

Ⅳ期非小细胞肺癌预后影响因素分析

Objective: To investigate the prognostic factors for stage Ⅳ non-small cell lung cancer (NSCLC) with distant metastasis and establish a reliable model of clinical prognostic index.Methods: From January 1990 to April 2005,313 primary NSCLC patients with metastasis,who had been treated in Shanghai Chest Hospital,were reviewed.Survival time was estimated according to the Kaplan-Meier method.Cox proportional hazard regression model was used for multivariate analysis.Results: Among the 313 cases of non-small cell lung cancer (NSCLC) at stage Ⅳ,there were 218 and 95 patients with metastasis to single and different organs,respectively.The overall median survival time for all 313 cases of NSCLC patients was 10.8 (9.00,12.30)months and the overall 1-,2-,3-,4- and 5-year survival rate was 45%,18%,12%,4% and 0%.There were 63,174,127,36,18,11 and 5 patients with metastasis to brain (20.13%),bone (55.59%),lung (40.58%),liver (11.50%),adrenal gland (5.75%),subcutaneous (3.51%) and others,respectively.The survival time was shortest in subcutaneous metastasis (4.6 months),and liver 7.0 months,brain 8.0 months,adrenal gland 8.6 months,bone 10.6 months,lung 11.8 months.Kaplan-Meier estimation showed that patients anatomic typing,KPS,numbers of organ with metastasis,appetite,liver,adrenal gland and subcutaneous metastasis,body weight loss,smoking,index of smoking,chemotherapy,cycles of chemotherapy were the predictors of survival.Multivariate analysis showed survival statistically significant correlation with anatomic typing,KPS,appetite,liver and subcutaneous metastasis,body weight loss,cycles of chemotherapy.The relative risk (RR) was 1.51,1.97,1.55,1.67,2.56,and 2.56 respectively.Conclusion: Survival time decreases distinctly in patients who had distant metastasis to more than two different organs (P＜0.01).Bone is the commonest organ for distant metastasis in lung cancer.The prognosis is poor when lung cancer appears subcutaneous metastasis and liver metastasis.Independent prognostic factors in patient with stage Ⅳ non-small cell lung cancer were liver and subcutaneous metastasis,anatomic typing,KPS,appetite,body weight loss,cycles of chemotherapy.     

69例局部复发鼻咽癌调强放疗疗效及预后分析

目的回顾性分析局部复发鼻咽癌调强放疗的疗效及影响预后的相关因素。方法 69例局部复发鼻咽癌患者均行调强放疗,再程放疗pGTV总剂量为49.5～77.4Gy(中位剂量为66Gy),每次分割剂量1.86～2.5Gy(中位2.1Gy)。48例接受1～6个周期以铂类为基础的化疗。结果全组患者的中位随访时间为20个月,截止末次随访日期,死亡24例(34.8%)。1、2年局部无进展生存率、无远处转移生存率及总生存率分别为92.9%、81.8%、81.8%和88.8%、65.5%、65.5%。单因素分析结果显示,首程放疗方式(P=0.004)和再程放疗总剂量(P=0.011)与生存期相关;多因素分析发现影响局部复发鼻咽癌的独立预后因素有首程放疗方式(P=0.004)和再程放疗总剂量(P=0.004)。放疗期间的急性毒副反应均可耐受。结论 IMRT是局部复发鼻咽癌的有效治疗手段,可提高患者的生存率。首程放疗方式和再程放疗总剂量是影响患者生存时间的独立预后因素。     

Stage III non-small-cell lung cancer treated with high-dose hyperfractionated radiation therapy and concurrent low-dose daily chemotherapy with or without weekend chemotherapy: retrospective analysis of 301 patients

We investigated the outcome in patients with stage III non-small-cell lung cancer (NSCLC) treated with high-dose hyperfractionated radiation therapy (Hfx RT) and concurrent chemotherapy (CHT) consisting of carboplatin (C) and etoposide (E). During three prospective randomized phase III and one prospective phase II study enrolling a total of 536 patients, 301 patients were treated with high-dose Hfx RT (69.6 Gy) and either low-dose daily CE (50 mg each) (n = 163) or daily CE (30 mg each) accompanied by "weekend" CE (100 mg of each on Saturdays and Sundays) (n = 138). The median survival time for all 301 patients is 22 months and 5-year survival is 24%. Median local recurrence-free survival (LRFS) time is 21 months and 5-year local recurrence-free survival is 32%. The median time to distant metastasis is 25 months, and 5-year distant metastasis-free survival (DMFS) is 35%. Only the type/schedule of CHT administration did not influence overall survival, LRFS, and DMFS. On multivariate analyses using these three endpoints, age stage, interfraction interval, and type/schedule of CHT administration did not predict survival, LRFS, and DMFS, while gender, KPS, and weight loss did. Only high grade hematologic toxicity was more frequent in weekend CHT group. High dose Hfx RT and concurrent low-dose daily CE with or without weekend CE is an active treatment approach in stage III NSCLC that led to high overall survival, LRFS, and DMFS rates.     

Long-term survival in patients with synchronous, solitary brain metastasis from non-small-cell lung cancer treated with radiosurgery

PURPOSE: To report the outcome of patients with synchronous, solitary brain metastasis from non-small-cell lung cancer (NSCLC) treated with gamma knife stereotactic radiosurgery (GKSRS). PATIENTS AND METHODS: Forty-two patients diagnosed with synchronous, solitary brain metastasis from NSCLC were treated with GKSRS between 1993 and 2006. The median Karnofsky performance status (KPS) was 90. Patients had thoracic Stage I-III disease (American Joint Committee on Cancer 2002 guidelines). Definitive thoracic therapy was delivered to 26/42 (62%) patients; 9 patients underwent chemotherapy and radiation, 12 patients had surgical resection, and 5 patients underwent preoperative chemoradiation and surgical resection. RESULTS: The median overall survival (OS) was 18 months. The 1-, 2-, and 5-year actuarial OS rates were 71.3%, 34.1%, and 21%, respectively. For patients who underwent definitive thoracic therapy, the median OS was 26.4 months compared with 13.1 months for those who had nondefinitive therapy, and the 5-year actuarial OS was 34.6% vs. 0% (p < 0.0001). Median OS was significantly longer for patients with a KPS >or=90 vs. KPS < 90 (27.8 months vs. 13.1 months, p < 0.0001). The prognostic factors significant on multivariate analysis were definitive thoracic therapy (p = 0.020) and KPS (p = 0.001). CONCLUSIONS: This is one of the largest series of patients diagnosed with synchronous, solitary brain metastasis from NSCLC treated with GKSRS. Definitive thoracic therapy and KPS significantly impacted OS. The 5-year OS of 21% demonstrates the potential for long-term survival in patients treated with GKSRS; therefore, patients with good KPS should be considered for definitive thoracic therapy.     

Postoperative radiotherapy in thymic carcinoma: treatment results and prognostic factors

PURPOSE: To analyze the treatment results and prognostic factors of patients with primary thymic carcinoma treated by total or subtotal tumor resection followed by radiotherapy alone. METHODS AND MATERIALS: Between October 1987 and October 1997, 26 patients with thymic carcinoma were treated with complete or incomplete surgical resection and postoperative adjuvant irradiation without chemotherapy. The radiation was delivered with 10-MV X-ray given 5 days per week at 1.8 to 2 Gy per fraction. Total doses ranged from 40 to 70 Gy. All patients had at least 40 months of follow-up. RESULTS: The 5-year overall survival rate, local control rate, and distant metastasis-free rate were 77%, 91%, and 57%, respectively. Several prognostic factors, including sex, age, extent of resection (total resection vs. subtotal resection), Masaoka staging (early Stage I + II vs. advanced Stage III + IV), pathology (low-grade vs. high-grade), and postoperative radiation dose (> or =60 Gy vs. <60 Gy), were evaluated in univariate analysis. The Masaoka staging system was the only statistically significant predictor in overall survival rate (p = 0.0482) and distant metastasis-free rate (p = 0.0193). CONCLUSIONS: The Masaoka staging system is the most important prognostic factor in primary thymic carcinoma patients receiving postoperative radiotherapy alone. For resectable tumors, surgery and postoperative radiotherapy can achieve good local control, but the distant metastatic rate is still high. Further investigation of more effective chemotherapy is needed.     

Prognostic factors in patients with stage IV non-small cell lung cancer

Lung cancer is the leading cause of cancer deaths among both men and women over the world. In 2002, lung can- cer accounted for more deaths than breast cancer, prostate cancer, and colon cancer combined[1]. Non-small cell lung cancer (NSCLC) represents 75%–85% of all lung cancers. Lung cancer is hard to discovered until it’s at an advanced stage and the outlook for recovery is poor. Approximately two-thirds of NSCLC patients have advanced-stage at di- agnosis. Stage IV NSCLC denotes …     

Prognostic Significance of Weight Gain During Definitive Chemoradiotherapy for Locally Advanced Non–Small-Cell Lung Cancer

BackgroundThe successful treatment of locally advanced non–small-cell lung cancer (NSCLC) with chemoradiotherapy (CRT) is still compromised by poor locoregional and distant control rates. Given the morbidity associated with treatment, it is critical to determine clinical prognostic factors to risk stratify patients before and after aggressive therapy. This study aimed to discern the prognostic value of weight gain during CRT in patients with locally advanced NSCLC.Patients and MethodsThis was a retrospective analysis of 92 patients treated with definitive split-course CRT between 2004 and 2010 at Rush University Medical Center. Weight gain was defined as a weight change greater than the highest quartile of change between the start and finish of CRT (4.5 lb). Overall survival (OS), locoregional progression-free survival (PFS), and distant metastasis-free survival (DMFS) were determined using Kaplan-Meier analysis, and the cumulative incidences of locoregional and distant recurrence were calculated. Cox regression (multivariate analysis) was used to determine independent predictors of OS.ResultsWith a median follow-up of 50 months for surviving patients, the median, 3- and 5-year OS probabilities were 25 months, 37%, and 29%, respectively. The 3-year cumulative risks of locoregional and distant metastases were 51% and 64%. Patients who experienced weight gain were significantly more likely to survive (3-year OS, 55% vs. 31%; P = .04) and prolonged DMFS resulted. Weight gain was the only significant predictor of survival on multivariate analysis.ConclusionsWeight gain during split-course CRT was associated with superior OS and DMFS. The presence of weight gain may have utility in risk stratification after CRT as well as in identifying novel treatment approaches for patients with locally advanced NSCLC.     

Is prolonged survival possible for patients with supraclavicular node metastases in non-small cell lung cancer treated with chemoradiotherapy?: Analysis of the Radiation Therapy Oncology Group experience.

PURPOSE: To determine if patients with non-small cell lung carcinoma (NSCLC) and positive supraclavicular nodes (SN+) have a similar outcome to other patients with Stage IIIB NSCLC (SN-) when treated with modern chemoradiotherapy. METHODS AND MATERIALS: Using the Radiation Therapy Oncology Group (RTOG) database, data were retrospectively analyzed from five RTOG trials studying chemoradiotherapy for NSCLC: 88-04, 88-08 (chemo-RT arm), 90-15, 91-06, 92-04. Comparisons were made between the SN+ and SN- subgroups with respect to overall survival, progression-free survival (PFS), and metastases-free survival (MFS) using the log rank test. Cox multivariate proportional hazards regression analysis was used to determine the effect of several potential confounding variables, including histology (squamous vs. nonsquamous), age (>60 vs. < or = 60), Karnofsky Performance Status (KPS) (<90 vs. > or = 90), weight loss (> or = 5% vs. <5%), and gender. RESULTS: A total of 256 Stage IIIB patients were identified, of whom 47 had supraclavicular nodes (SN+) and 209 did not (SN-). Statistically significantly more SN+ patients had nonsquamous histology (p = 0.05); otherwise, known prognostic factors were well balanced. The median survival for SN+ patients was 16.2 months, vs. 15.6 months for SN- patients. The 4-year actuarial survival rates were 21% and 16% for SN+ and SN- patients respectively (p = 0.44). There was no statistically significant difference in the 4-year PFS rates (19% vs. 14%, p = 0.48). The Cox analysis did not show the presence or absence of supraclavicular nodal disease to be a prognostic factor for survival, MFS, or PFS. The only statistically significant factor on multivariate analysis was gender, with males having a 40% greater risk of mortality than females (p = 0.03). There were no clinically significant differences in toxicity when comparing SN+ vs. SN- patients. Among the 47 SN+ patients, there were no reported cases of brachial plexopathy or other > or = Grade 2 late neurologic toxicity. CONCLUSIONS: When treated with modern chemoradiotherapy, the outcome for patients with supraclavicular metastases appears to be similar to that of other Stage IIIB patients. SN+ patients should continue to be enrolled in trials studying aggressive chemoradiotherapy regimens for locally advanced NSCLC.     

Clinical prognostic factors in patients with locally advanced (stage III) nonsmall cell lung cancer treated with hyperfractionated radiation therapy with and without concurrent chemotherapy: single-Institution Experience in 600 Patients

BACKGROUND:

Influence of potential clinical prognostic factors on overall survival (OS), local progression‐free survival (PFS), and distant metastasis‐free survival (MFS) in patients with locally advanced nonsmall cell lung cancer treated with hyperfractionated radiation therapy (HFX RT) with or without concurrent chemotherapy was investigated.

METHODS:

Three phase 3 and 2 phase 2 studies have been designed and executed with a total of 600 patients. HFX RT alone was given in 127 and HFX RT‐chemotherapy was given in 473 patients. HFX RT doses were either 64.8 grays (Gy) or 69.6 Gy using 1.2 Gy twice daily, or 67.6 Gy using 1.3 Gy twice daily. Chemotherapy consisted of concurrent carboplatin and etoposide in 409 patients and concurrent carboplatin and paclitaxel in 64 patients. Sex, age, Karnofsky performance score (KPS), weight loss (>5%), stage, histology, interfraction interval, and treatment (the addition of concurrent chemotherapy) were investigated as potential prognostic factors.

RESULTS:

The median OS, median local PFS, and median distant MFS times were 19, 21, and 23 months, respectively. Five‐year OS, local PFS, and distant MFS rates were 19%, 29%, and 35%, respectively. Univariate and multivariate analysis showed that only age did not influence OS and local PFS, whereas female sex, lower KPS, less pronounced weight loss, lower stage, squamous histology, shorter interfraction interval, and treatment independently predicted better OS and local PFS. Only age and treatment did not influence distant MFS, whereas histology was of borderline significance.

CONCLUSIONS:

This study identified independent prognosticators of treatment outcome. These results may have implications for future studies in this disease. Cancer 2011. © 2011 American Cancer Society.     

Ⅳ期NSCLC化疗同期3DRT的前瞻性多中心Ⅱ期临床研究-PPRA-RTOG003

目的 探讨Ⅳ期NSCLC化疗同期3DRT的疗效和安全性。方法 2008-2012年共 198例患者符合以下入组标准:年龄 18~80岁,KPS≥70,无放化疗禁忌,组织或细胞病理学确诊的初治NSCLC,临床分期为Ⅳ期,转移器官数≤3个。主要研究终点为生存率及急性不良反应。结果 随访率98.5%,3年样本量为 165例。中位OS期和PFS期分别为13.0(95%CI为 11.7~14.3) 和9.0(95%CI为 7.7~10.3)个月,1、2、3年OS率分别为53.5%、15.8%、9.2%。多因素分析显示原发肿瘤体积<134 cm³(P=0.008)、治疗后KPS稳定或增加(P=0.010)及放疗剂量≥63 Gy (P=0.014)是延长生存因素。3-4级中性粒细胞降低占37.9%、血小板降低占10.1%、血红蛋白降低占6.9%,3级急性放射性食管炎和肺炎分别占2.5%和6.6%。主要死因为远处转移,仅10%单纯复发死亡。     

三维适形放疗非小细胞肺癌预后因素分析

目的回顾性分析非小细胞肺癌(NSCLC)三维适形放疗(3DCRT)疗效及其预后因子。方法接受3DCRT的178例NSCLC中男136例,女42例,中位年龄65岁。放疗剂量2～3 Gy/次,6次/周,总剂量60～75Gy。对相关指标进行单因素、多因素分析,并用预后指数模型综合评价放疗疗效。结果中位随访期16个月(14～38个月),1、2年生存率分别为62.4%、39.7%,中位生存时间16个月。单因素分析显示性别、疗前体重下降、病理类型、T分期、原发肿瘤最大横径、GTV体积、照射总剂量对生存期有影响。多因素分析显示疗前体重下降、病理类型、GTV体积和照射总剂量为独立的预后因子,综合以上4种因素的预后指数模型能较好地区分不同的预后亚组。结论疗前体重下降、病理类型、GTV体积及照射总剂量是NSCLC患者3DCRT的独立预后因子,预后指数模型比单个因素能更好地反映3DCRT预后。     

Induction chemotherapy plus three-dimensional conformal radiation therapy in the definitive treatment of locally advanced non-small-cell lung cancer

PURPOSE: To evaluate our institution's experience using chemotherapy in conjunction with three-dimensional conformal radiation therapy (3D-CRT). METHODS AND MATERIALS: From 1991 to 1998, 152 patients with Stage III non-small-cell lung cancer (NSCLC) were treated with 3D-CRT at Memorial Sloan-Kettering Cancer Center. A total of 137 patients (90%) were surgically staged with either thoracotomy or mediastinoscopy. The remainder were staged radiographically. Seventy patients were treated with radiation therapy alone, and 82 patients received induction chemotherapy before radiation. The majority of chemotherapy-treated patients received a platinum-containing regimen. Radiation was delivered with a 3D conformal technique using CT-based treatment planning. The median dose in the radiation alone group was 70.2 Gy, while in the combined modality group, it was 64.8 Gy. RESULTS: The median follow-up time was 30.5 months among survivors. Stage IIIB disease was present in 36 patients (51%) in the radiation-alone group and 57 patients (70%) in the combined-modality group. Thirty-nine patients had poor prognostic factors (KPS < 70 or weight loss > 5%), and they were equally distributed between the two groups. The median survival times for the radiation-alone and the combined-modality groups were 11.7 months and 18.1 months, respectively (p = 0.001). The 2-year rates of local control in the radiation-alone and combined-modality groups were 35.4% and 43.1%, respectively (p = 0.1). Grade 3 or worse nonhematologic toxicity occurred in 20% of the patients receiving radiation alone and in 16% of those receiving chemotherapy and radiation. Overall, there were only 4 cases of Grade 3 or worse esophagitis. CONCLUSION: Despite more Stage IIIB patients in the combined-modality group, the addition of chemotherapy to 3D-CRT produced a survival advantage over 3D-CRT alone in Stage III NSCLC without a concomitant increase in toxicity. Chemotherapy thus appears to be beneficial, even in patients who are receiving higher doses of radiation therapy than are typically given with conventional techniques. Because locoregional failure remains a major challenge in patients with advanced disease, 3D-CRT in conjunction with chemotherapy may allow safe treatment to the dose levels required to further enhance local control.     

Clinical prognostic factors in patients with malignant glioma treated with combined modality approach

The impact of various clinical pretreatment prognostic factors in patients with malignant glioma treated with a combined modality approach was investigated in 229 patients treated on four consecutive prospective phase II studies. The median survival time for all 229 patients is 14 months, and 2- and 5-year survival rates are 34%, and 9%, respectively. The median time to tumor progression is 14 months, and 2- and 5-year progression-free survival rates are 32%, and 9%, respectively. Females did better than males, while patients 55 years or less did better than those more than 55 years. Patients with Karnofsky performance status (KPS) 80 to 100 did better than those with KPS 50 to 70 as well as did patients having preoperative tumor sizes 4 cm or less when compared to those with larger tumors. Frontal tumor location as well as more extensive surgery favorably influenced survival. Patients harboring anaplastic astrocytoma fared significantly better than those with glioblastoma multiforme. Both univariate and multivariate Cox analyses confirmed independent influence of these prognosticators. When progression-free survival was used as an endpoint, all seven variables remained independent prognosticators. This study showed that sex, age, KPS, tumor size, tumor location, histology, and extent of surgery are independent prognosticators in patients with malignant glioma treated with combined modality approach.     

Lack of effect of tumor size on the prognosis of carcinoma of the uterine cervix Stage IB and IIA treated with preoperative irradiation and surgery.

PURPOSE: The purpose of this analysis was to evaluate the prognostic significance of cervical tumor size in patients with Stages Ib and IIa carcinoma of the cervix treated with preoperative irradiation and radical or conservative hysterectomy. METHODS AND MATERIALS: This study is a retrospective analysis of 177 patients. One hundred forty-one patients had Stage Ib and 36 patients had Stage IIa carcinoma of the cervix. All patients were treated with preoperative irradiation and surgery. Radiation therapy consisted of external pelvic irradiation and intracavitary brachytherapy; total doses ranged from 30 to 60 Gy to the pelvic sidewall and 60 to 70 Gy to point A. Surgery consisting of radical hysterectomy and lymph node dissection or a conservative hysterectomy and lymph node dissection was performed 4 to 6 weeks after completion of irradiation. RESULTS: The 5-year progression-free survivals were 80% for Stage Ib and 63% for Stage IIa (p = 0.03). The 5-year cumulative pelvic failure rates for Stage Ib were 16% for tumors <3 cm and 9% for tumors >3 cm (p = 0.90). The 5-year cumulative pelvic failure rates for Stage IIa were 22% for tumors <3 cm and 22% for tumors >3 cm (p = 0.75). The corresponding cumulative distant metastasis failure rates at 5 years for Stage Ib were 21% for tumors <3 cm and 21% for tumors >3 cm (p = 0.60). For patients with Stage IIa disease, the 5-year cumulative distant metastasis rates were 33% for tumors <3 cm and 36% for tumors >3 cm (p = 0.70). A multivariate analysis was performed to evaluate prognostic factors for the endpoint of progression-free survival. The variables that were analyzed were patient age, tumor histology, tumor size, clinical stage, point A and pelvic lymph node irradiation dose, and cervical tumor status and pelvic lymph node status at the time of hysterectomy. The variables that were found to be of independent significance for progression-free survival by multivariate analysis were pelvic lymph node irradiation dose (p <0.001), pelvic lymph node status at the time of hysterectomy (p = 0.01), and clinical stage (p = 0.02). Cervical tumor size at the time of diagnosis and the presence of tumor cells in the cervix in the hysterectomy specimen was not an independent prognostic factor by multivariate analysis. The overall severe complication rate was 11% for all patients. CONCLUSIONS: For this population of patients treated with preoperative irradiation and surgery, pelvic lymph node status at the time of hysterectomy and the preoperative irradiation dose to the pelvic lymph nodes are independent predictors of progression-free survival and the development of distant metastasis. The pretreatment cervical tumor size is of less importance for predicting progression-free survival and the development of distant metastasis but clinical stage is an important prognostic variable. These results are in contrast with those of surgery or irradiation alone, in which primary tumor size is a critical prognostic factor for all outcome parameters.     

Clinical Outcome of Helical Tomotherapy for Inoperable Non-Small Cell Lung Cancer: The Kyung Hee University Medical Center Experience

Background: Published studies on clinical outcome of helical tomotherapy for lung cancer are limited. Thepurpose of this study was to evaluate clinical outcomes and treatment-related toxicity in inoperable non-smallcell lung cancer (NSCLC) patients treated with helical tomotherapy in Korea. Materials and Methods: Twentysevenpatients with NSCLC were included in this retrospective study. Radiotherapy was performed using helicaltomotherapy with a daily dose of 2.1-3 Gy delivered at 5 fractions per week resulting in a total dose of 62.5-69.3Gy. We assessed radiation-related lung and esophageal toxicity, and analyzed overall survival, locoregionalrecurrence-free survival, distant metastasis-free survival, and prognostic factors for overall survival. Results:The median follow-up period was 28.9 months (range, 10.1-69.4). The median overall survival time was 28.9months, and 1-, 2-, and 3-year overall survival rates were 96.2%, 92.0%, and 60.0%. The median locoregionalrecurrence-free survival time was 24.3 months, and 1-, 2-, and 3-year locoregional recurrence-free survival rateswere 85.2%, 64.5%, and 50.3%. The median distant metastasis-free survival time was 26.7 months, and 1-, 2-,and 3-year distant metastasis-free survival rates were 92.3%, 83.9%, and 65.3%, respectively. Gross tumorvolume was the most significant prognostic factor for overall survival. No grade 4 or more toxicity was observed.Conclusions: Helical tomotherapy in patients with inoperable NSCLC resulted in high survival rates with anacceptable level of toxicity, suggesting it is an effective treatment option in patients with medically inoperableNSCLC.     

Treatment results for nasopharyngeal carcinoma in the modern era: the Hong Kong experience

PURPOSE: To analyze the treatment results achievable for nasopharyngeal carcinoma in the modern era to identify the key failures for future improvement and to provide an updated baseline for future trials. METHODS AND MATERIALS: The results of 2687 consecutive patients treated at all public oncology centers in Hong Kong during 1996-2000 were retrospectively analyzed. The stage distribution (by American Joint Committee on Cancer and International Union Against Cancer staging system, 1997) was 7% Stage I, 41% Stage II, 25% Stage III, and 28% Stage IVA-B. All patients were irradiated with 6-MV photons and the median total dose was 66 Gy. Only 23% of patients had additional treatment with chemotherapy. RESULTS: The 5-year local, nodal, and distant failure-free rates were 85%, 94%, and 81%, respectively; patients with local failure had significantly higher risk of nodal and distant failures. The 5-year progression-free, overall, and cancer-specific survival rates were 63%, 75%, and 80%, respectively. The presenting stage was the most important prognostic factor for all endpoints: with overall survival decreasing from 90% for Stage I to 58% for Stage IVA-B. The results achieved by the 2070 patients treated by radiotherapy alone were almost identical to that of the whole series, the distant failure-free rate among patients with locoregional control was 89% for Stage I-II and 75% for Stage III-IVB. The 860 patients (32%) staged with magnetic resonance imaging achieved significantly better results than those staged by computed tomography, the overall survival being 93% vs. 83% for Stages I-II, and 72% vs. 63% for Stages III-IVB (p = 0.001). CONCLUSIONS: Treatment results for nasopharyngeal carcinoma have substantially improved in the modern era; future trials should be based on updated baseline results. Further reduction of distant failure is important for future breakthrough, particularly for patients with advanced disease.     

Has 3-D conformal radiotherapy (3D CRT) improved the local tumour control for stage I non-small cell lung cancer?

AIMS AND BACKGROUND: The high local failure rates observed after radiotherapy in stage I non-small cell lung cancer (NSCLC) may be improved by the use of 3-dimensional conformal radiotherapy (3D CRT). MATERIALS AND METHODS: The case-records of 113 patients who were treated with curative 3D CRT between 1991 and 1999 were analysed. No elective nodal irradiation was performed, and doses of 60Gy or more, in once-daily fractions of between 2 and 3Gy, were prescribed. RESULTS: The median actuarial survival of patients was 20 months, with 1-, 3- and 5-year survival of 71, 25 and 12%, respectively. Local disease progression was the cause of death in 30% of patients, and 22% patients died from distant metastases. Grade 2-3 acute radiation pneumonitis (SWOG) was observed in 6.2% of patients. The median actuarial local progression-free survival (LPFS) was 27 months, with 85 and 43% of patients free from local progression at 1 and 3 years, respectively. Endobronchial tumour extension significantly influenced LPFS, both on univariate (P=0.023) and multivariate analysis (P=0.023). The median actuarial cause-specific survival (CSS) was 19 months, and the respective 1- and 3-year rates were 72 and 30%. Multivariate analysis showed T2 classification (P=0.017) and the presence of endobronchial tumour extension (P=0.029) to be adverse prognostic factors for CSS. On multivariate analysis, T-stage significantly correlated with distant failure (P=0.005). CONCLUSIONS: Local failure rates remain substantial despite the use of 3D CRT for stage I NSCLC. Additional improvements in local control can come about with the use of radiation dose escalation and approaches to address the problem of tumour mobility.     

Comorbidity and Karnofksy performance score are independent prognostic factors in stage III non-small-cell lung cancer: an institutional analysis of patients treated on four RTOG studies. Radiation Therapy Oncology Group

PURPOSE: To determine the prognostic role of comorbidity in Stage III non-small cell lung cancer (NSCLC) treated definitively with radiotherapy alone. METHODS AND MATERIALS: A total of 112 patients with clinical Stage III NSCLC (American Joint Commission on Cancer 1997) enrolled in four Radiation Therapy Oncology Group studies (83-11, 84-03, 84-07, and 88-08 nonchemotherapy arms) at a single institution were analyzed retrospectively for overall survival (OS) and comorbidity. Of the 112 patients, 105 (94%) completed their assigned radiotherapy. The median assigned dose was 50.4 Gy to the lymphatics (range 45-50.4 Gy) and 70.2 Gy to the primary tumor (range 60-79.2 Gy). Comorbidity was rated retrospectively using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G) and Charlson scales. Karnofsky performance scores (KPSs) and weight loss were prospectively recorded. Because only 8 patients had a KPS of <70, these patients were combined with patients who had a KPS of 70. The OS of this group was compared with that of the patients with better KPSs (>70). RESULTS: The median survival was 10.39 months (range 7.87-12.91). The 2-, 3-, and 5-year OS rate was 20.5%, 12.5%, and 7.1%, respectively. On univariate analysis, clinical stage (IIIA vs. IIIB) was found to be a statistically significant factor influencing OS (p = 0.026), and the histologic features, grade, tumor size as measured on CT scans, age, tobacco use, weight loss >or=5%, and total dose delivered to the primary tumor were not. A KPS of 2 (p <0.0001) were associated with statistically significant inferior OS. Multivariate analysis with clinical stage, KPS, and comorbidity (severity index) of all patients showed that a KPS 2 were independently associated with inferior OS; clinical tumor stage was not found to be an independent prognostic factor. CONCLUSION: KPS and comorbidity are important independent prognostic factors in Stage III NSCLC. Comorbidity should be included in protocols studying advanced stage NSCLC and used for stratification.