A phase II study of continuous concurrent thoracic radiotherapy in combination with mitomycin, vindesine and cisplatin in unresectable stage III non-small cell lung cancer

The split-course concurrent thoracic radiation therapy (TRT) and full-dose chemotherapy for unresectable stage III non-small cell lung cancer (NSCLC) has produced promising results by comparison with the sequential approach. Instead of split-course radiation, we conducted a phase II study to investigate the feasibility of continuous concurrent TRT and chemotherapy. Twenty-two patients with unresectable NSCLC were enrolled onto a phase II study of continuous concurrent radiotherapy and chemotherapy. Treatment consisted of two courses of cisplatin (80 mg/m(2) on days 1 and 29), vindesine (3 mg/m(2) on days 1, 8, 29 and 36), and mitomycin (8 mg/m(2) on days 1 and 29). TRT began on day 2 at a dose of 60 Gy (2 Gy per fraction and 5 fractions per week for a total of 30 fractions). Of 22 patients assessable for response, none achieved a CR and 17 (77.3%) achieved a PR with an overall response rate of 77.3% (95% confidence interval, 54.6-92.2%). Grade 3 or 4 leukopenia was observed in 5/13 (81.8%) patients. Six patients (27.3%) experienced > or = grade 3 thrombocytopenia. Non-hematological toxicity was relatively mild. The overall median survival time was 19.0 months and the 1- and 2-year survival rates were 84.8 and 34.5%, respectively. It was possible to administer two courses of chemotherapy in 18 patients (81.8%) as planned. Nineteen (86.4%) of the 22 patients received the planned 60 Gy radiation. It seems to be difficult to administer the planned treatment without any interruption for the majority of patients. However, in the selected patients who completed the 60 Gy TRT, nearly half of the patients completed TRT without interruption. This combination regimen is considered to be feasible on condition that the stopping rule of the treatment is followed. We recommend administering radiotherapy continuously as far as possible.     

Phase I study of cisplatin, vinorelbine, and concurrent thoracic radiotherapy for unresectable stage III non-small cell lung cancer

To determine the recommended phase II dose of vinorelbine in combination with cisplatin and thoracic radiotherapy (TRT) in patients with unresectable stage III non-small cell lung cancer (NSCLC), 18 patients received cisplatin (80 mg/m2) on day 1 and vinorelbine (20 mg/m2 in level 1, and 25 mg/m2 in level 2) on days 1 and 8 every 4 weeks for 4 cycles. TRT consisted of a single dose of 2 Gy once daily for 3 weeks followed by a rest of 4 days, and then the same TRT for 3 weeks to a total dose of 60 Gy. Fifteen (83%) patients received 60 Gy of TRT and 14 (78%) patients received 4 cycles of chemotherapy. Ten (77%) of 13 patients at level 1 and all 5 patients at level 2 developed grade 3-4 neutropenia. Four (31%) patients at level 1 and 3 (60%) patients at level 2 developed grade 3-4 infection. None developed > or = grade 3 esophagitis or lung toxicity. Dose-limiting toxicity was noted in 33% of the patients in level 1 and in 60% of the patients in level 2. The overall response rate (95% confidence interval) was 83% (59-96%) with 15 partial responses. The median survival time was 30.4 months, and the 1-year, 2-year, and 3-year survival rates were 72%, 61%, and 50%, respectively. In conclusion, the recommended dose is the level 1 dose, and this regimen is feasible and promising in patients with stage III NSCLC.     

Phase II trial of daily low-dose carboplatin and thoracic radiotherapy in elderly patients with locally advanced non-small cell lung cancer

BACKGROUND: The purpose of this study was to investigate the feasibility of concurrent thoracic radiotherapy (TRT) and daily low-dose carboplatin (CBDCA) in elderly patients with locally advanced non-small cell lung cancer (NSCLC) and to estimate tumor response, toxicity and survival. METHODS: Forty patients were entered in a multicenter phase II study. All were patients with pathologically documented unresectable stage IIIA or IIIB or medically inoperable stage I, II NSCLC. CBDCA 30 mg/m2 was given on days 1-5 in weeks 1-4 concurrently with TRT, mainly for radiosensitization. TRT was started 1 h after CBDCA (30 min infusion) was given. TRT was given in 2 Gy/fraction/day, 5 days a week for a total of 50-60Gy. RESULTS: Thirty-eight patients were assessable for treatment response and toxicity. One patient had a CR and 18 patients PRs with a response rate of 50% (95% CI, 33.4-66.6%). The main toxicities were hematological toxicity. Other toxicities were grade > or =2 esophagitis in one patient, grade 3 nausea/vomiting in one and grade > or =3 pulmonary toxicity in two. There was one treatment-related death due to pulmonary toxicity. For stage IIIA + IIIB patients, the median survival time was 15.1 months and 1-and 2-year actuarial survival rates were 52.6 and 20.5%, respectively. For stage I + II patients, 1- and 3-year actuarial survival rates were 90.9 and 69.3%, respectively. CONCLUSIONS: The data suggest that TRT with daily low-dose CBDCA in elderly patients is effective and feasible because of its low toxicity and survival.     

Ⅳ期非小细胞肺癌化疗同期胸部三维放疗的前瞻性临床研究(一)——疗效与不良反应

目的 研究Ⅳ期非小细胞肺癌(NSCLC)化疗同期胸内病灶三维放疗的疗效和安全性.方法 2003-2010年共入组201例,可疗效分析182例,安全性分析201例.化疗以铂类为基础二药联合方案,中位周期数为4个.胸内病灶中位计划靶体积剂量为63 Gy.分析患者的生存情况,胃肠道、血液学不良反应,放射性肺炎和食管炎.用Kaplan-Meier法进行生存分析,Cox回归模型进行多因素分析.结果 201例的随访率为97.5％,随访满＜1、1～2、≥3年者分别为201、170、134例.全组182例中4～5个周期化疗同期三维放疗和同期三维放疗≥63 Gy的1、2、3年生存率以及中位生存期(MST)分别为54％和66％、20％和23％、13％和19％以及14.3个月和16.1个月;相似放化疗强度下单器官和多器官转移的MST分别为13.0个月和8.5个月(x2=10.10,P=0.001);同期放疗≥63 Gy 和＜63 Gy的MST在全组、4～5个周期化疗的分别为14.9个月和8.4个月(x2=20.48,P=0.000)、16.1个月和8.8个月(x2 =11.75,P=0.001),单器官、多器官的分别为16.0个月和9.0个月(x2=10.51,P=0.001)、11.0个月和7.0个月(x2=7.90,P=0.005).多因素分析显示4～5个周期化疗同期放疗≥63 Gy(β=0.243,P=0.019)、治疗后卡氏评分变化(β=1.268,P=0.000)对生存有影响.201例患者的2+3级胃肠反应发生率为45.0％;3+4级白细胞、血小板、血红蛋白不良反应发生率分别为35.0％、18.0％、15.0％;2+3级放射性肺炎和食管炎发生率分别为9.5％和13.4％.结论 Ⅳ期NSCLC化疗同期原发灶高剂量三维放疗可能使生存期延长,不良反应可接受.     

High-dose 3-dimensional conformal radiotherapy with concomitant vinorelbine plus carboplatin in patients with non-small cell lung cancer: A feasibility study

The aim of this study was to evaluate the feasibility of high-dose 3-dimensional conformal radiotherapy (3DCRT) (70 Gy) with concomitant vinorelbine (NVB) plus carboplatin (CBP) chemotherapy in patients with non-small cell lung cancer (NSCLC). Patients with advanced NSCLC were treated with 3-dimensional conformal radiotherapy in conventional fractionation: 2 Gy/fraction, 1 fraction/day, 5 fractions/week; total dose 70 Gy. The radiotherapy planning of every case had met the following conditions: the percentage of total lung volume receiving 20 Gy (V20) ≤30% and the percentage of total lung volume receiving 30 Gy (V30) ≤20%. Chemotherapy was commenced on the first day of radiotherapy: NVB 25 mg/m(2), day 1 and day 8, CBP at AUC of 5 mg/ml(-1).min(-1), day 8, repeated for 28 days, two concomitant cycles during radiotherapy, and not more than 4 cycles following radiotherapy. A total of 37 patients were recruited and each of them completed the entire radiation procedure. No Grade V toxicity was observed within the group. The hematological toxicity rates were: Grade III/IV neutropenia was observed in 18.9% (7/37) of cases, Grade III/IV thrombocytopenia in 8.1% (3/37) of cases, but no cases of Grade III/IV anemia were noted. For non-hematological toxicities the rates were: Grade III radiation pneumonitis, 8.1% (3/37) of cases; Grade III radiation esophagitis, 13.5% (5/37); but no cases of Grade IV/V non-hematological toxicities. High-dose 3DCRT also achieved a favorable efficacy: the complete response (CR) rate was 13.5% (5/37) and the partial response (PR) rate was 64.9% (24/37). The total response (CR+PR) rate was 78.4% (29/37). The median survival time was 12 months and the 1-year overall survival rate was 45.1%. Given that 35% of patients in the study had stage IV disease, the survival results were comparable with other similar studies. In conclusion, in our small-sample exploratory study, the high-dose regimen of 70 Gy using 3DCRT with concomitant NVB plus CBP was feasible for patients with NSCLC. Further evaluation of this regimen is ongoing in a prospective controlled phase II trial.     

Phase I North Central Cancer Treatment Group Trial-N9923 of escalating doses of twice-daily thoracic radiation therapy with amifostine and with alternating chemotherapy in limited stage small-cell lung cancer

PURPOSE: The primary goal was to identify the maximum tolerable dose (MTD) of thoracic radiation therapy (TRT) that can be given with chemotherapy and amifostine for patients with limited-stage small-cell lung cancer (LSCLC). METHODS AND MATERIALS: Treatment began with two cycles of topotecan (1 mg/m(2)) Days 1 to 5 and paclitaxel (175 mg/m(2)) Day 5 (every 3 weeks) given before and after TRT. The TRT began at 6 weeks. The TRT was given in 120 cGy fractions b.i.d. and the dose escalation (from 4,800 cGy, dose level 1, to 6,600 cGy, dose level 4) followed the standard "cohorts of 3" design. The etoposide (E) (50 mg/day) and cisplatin (C) (3 mg/m(2)) were given i.v. before the morning TRT and amifostine (500 mg/day) was given before the afternoon RT. This was followed by prophylactic cranial irradiation (PCI). The dose-limiting toxicities (DLTs) were defined as Grade > or =4 hematologic, febrile neutropenia, esophagitis, or other nonhematologic toxicity, Grade > or =3 dyspnea, or Grade > or =2 pneumonitis. RESULTS: Fifteen patients were evaluable for the Phase I portion of the trial. No DLTs were seen at dose levels 1 and 2. Two patients on dose level 4 experienced DLTs: 1 patient had a Grade 4 pneumonitis, dyspnea, fatigue, hypokalemia, and anorexia, and 1 patient had a Grade 5 hypoxia attributable to TRT. One of 6 patients on dose level 3 had a DLT, Grade 3 esophagitis. The Grade > or =3 toxicities seen in at least 10% of patients during TRT were esophagitis (53%), leukopenia (33%), dehydration (20%), neutropenia (13%), and fatigue (13%). The median survival was 14.5 months. CONCLUSION: The MTD of b.i.d. TRT was 6000 cGy (120 cGy b.i.d.) with EP and amifostine.     

HI-CHART: a phase I/II study on the feasibility of high-dose continuous hyperfractionated accelerated radiotherapy in patients with inoperable non-small-cell lung cancer

PURPOSE: To determine the feasibility of high-dose continuous hyperfractionated accelerated radiotherapy in patients with inoperable non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: In a prospective, Phase I/II study, according to the risk for radiation pneumonitis, three risk groups were defined: V(20) <25%, V(20) 25-37%, and V(20) >37%. The dose was administered in three steps from 61.2 Gy/34 fractions/23 days to 64.8 Gy/36 fractions/24 days to 68.40 Gy/38 fractions/25 days (1.8 Gy b.i.d. with 8-h interval), using a three-dimensional conformal technique. Only the mediastinal lymph node areas that were positive on the pretreatment (18)F-deoxy-D-glucose positron emission tomography scan were included in the target volume. The primary endpoint was toxicity. RESULTS: A total of 48 Stage I-IIIB patients were included. In all risk groups, 68.40 Gy/38 fractions/25 days could be administered. Maximal toxicity according to the risk groups was as follows: V(20) <25% (n = 35): 1 Grade 4 (G4) lung and 1 G3 reversible esophageal toxicity; V(20) 35-37% (n = 12): 1 G5 lung and 1 G3 reversible esophageal toxicity. For the whole group, local tumor recurrence occurred in 25% (95% confidence interval 14%-40%) of the patients, with 1 of 48 (2.1%; upper one-sided 95% confidence limit 9.5%) having an isolated nodal recurrence. The median actuarial overall survival was 20 months, with a 2-year survival rate of 36%. CONCLUSIONS: High-dose continuous hyperfractionated accelerated radiotherapy up to a dose of 68.40 Gy/38 fractions/25 days (a biologic equivalent of approximately 80 Gy when delivered in conventional fractionation) in patients with inoperable NSCLC and a V(20) up to 37% is feasible.     

Mid-course thoracic radiotherapy with cisplatin-etoposide chemotherapy in limited-stage small-cell lung cancer

Combination chemoradiotherapy is a standard treatment for limited-stage small-cell lung cancer (LS-SCLC). However, there is still controversery about the optimal timing of thoracic radiotherapy (TRT). In this study, the outcome of 70 patients who had received TRT at a dose of median 50 Gy (range, 46–60 Gy) with a second or third cycle of chemotherapy (CHT) either concurrently (n=41) or sequentially (n=29) were analyzed retrospectively. All patients were administered a median of five cycles (range, four to six cycles) cisplatin plus etoposide (EP) CHT. Prophylactic cranial radiotherapy was delivered to 30 (43%) patients. The median follow-up for all patients was 15 mo (range, 6–60 mo). The median overall survival was 19 mo in the concurrent arm vs 15 mo in the sequential arm. The 2-yr local control, disease-free survival, and overall survival rates were 60%, 19%, and 36%, respectively. The most common toxicity was esophagitis. However, there were no grade 3–4 esophagitis in either arm. Grade 3–4 hematologic toxicity, on the other hand, appeared significantly more in the concurrent arm (p<0.001). Mid-course of once-daily TRT at a moderate total dose with CHT failed to show any improvement in survival. Additionally, there were no differences between concurrent and sequential CHT with TRT. However, acceptable toxicity rates support the use of once-daily fractionation to higher total dose of TRT.     

73.6 Gy and beyond: hyperfractionated, accelerated radiotherapy for non-small-cell lung cancer.

PURPOSE: To assess results with twice-daily high-dose radiotherapy (RT) for non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Between 1991 and 1998, 94 patients with unresectable NSCLC were prescribed > or = 73.6 Gy via accelerated fractionation. Fifty were on a phase II protocol (P group); 44 were similarly treated off-protocol (NP group). The clinical target volume received 45 Gy at 1.25 Gy bid (6-hour interval). The gross target volume received 1.6 Gy bid to 73.6 to 80 Gy over 4.5 to 5 weeks using a concurrent boost technique. Overall survival (OS) and local progression-free survival (LPFS) were calculated by the Kaplan-Meier method. Median follow-up durations for surviving P and NP patients were 67 and 16 months, respectively. RESULTS: Total doses received were > or = 72 Gy in 97% of patients. The median OS by stage was 34, 13, and 12 months for stages I/II, IIIa, and IIIb, respectively. LPFS was significantly longer for patients with T1 lesions (median, 43 months) versus T2-4 (median, 7 to 10 months; P =.01). Results were similar in the P and NP groups. Acute grade > or = 3 toxicity included esophagus (14 patients; 15%), lung (three patients; 3% [one grade 5]), and skin (four patients; 4%). Grade > or = 3 late toxicity in 86 assessable patients included esophagus (three patients; 3%), lung (15 patients; 17% [three grade 5]), skin (five patients; 6%), heart (two patients; 2%), and nerve (one patient; 1%). CONCLUSION: This regimen yielded favorable survival results, particularly for T1 lesions. Acute grade > or = 3 toxicity seems greater than for conventional RT, though most patients recovered. Late grade > or = 3 pulmonary toxicity occurred in 17%. Because of continued locoregional recurrences, we are currently using doses > or = 86 Gy.     

Concurrent paclitaxel-cisplatin and twice-a-day irradiation in stage IIIA and IIIB NSCLC shows improvement in local control and survival with acceptable hematologic toxicity

Non-small-cell lung cancer (NSCLC) has one of the highest death rates among the various forms of cancer. In attempts to improve on this unsatisfactory outcome, different radiation schedules and chemo-therapy agents have been examined in phase II or III studies. These have led to modest improvements in local control and survival, but combined therapies are associated with substantial hematologic toxicity. In this phase II study, 80 consecutive stage IIIA or IIIB NSCLC patients were treated with concomitant chemotherapy and twice-a-day irradiation in a total dose of 60 Gy in 1.5 Gy fractions. Patients scheduled for surgery received 45 Gy only. Paclitaxel (30 mg/m 2 ) on days 1-4 and cisplatin (100 mg/m 2 ) on day 5 were administered in the first and fourth weeks of treatment. Granulocyte colony stimulating factor (30 ng/m 2 ) was given on days 10-15. The local control, the 1- and 2-year survival rates and the occurrence of acute hematologic toxicity in the non-surgically treated patients were examined. Fifty-two patients were treated without and 28 with surgery. Among the non-surgically treated cases, 43 were evaluable for response and 47 for acute toxicity during a median follow-up of 22 months. The rate of local control was 65% (28/43), and the 1- and 2-year survival rates proved to be 68% and 48%, respectively, with a median survival of 28 months. Severe acute grade 3-4 toxicities included grade 4 leukopenia in 6 cases (13%), grade 3 leukopenia in 4 cases (9%), grade 3 esophagitis in 3 cases (6%) and grade 3 anemia in 3 cases (6%). Our results and the relevant data from the literature support the application of twice-a-day irradiation with concomitant chemotherapy in stage IIIA and IIIB NSCLC. Local control and survival were improved relative to once-a-day irradiation with sequential or concomitant chemotherapy.     

Uracil/tegafur plus cisplatin with concurrent radiotherapy for locally advanced non-small-cell lung cancer: a multi-institutional phase II trial.

PURPOSE: To evaluate the efficacy and toxicity of a novel combination treatment using concurrent radiotherapy with cisplatin plus UFT, which is comprised of uracil and tegafur, in locally advanced non-small cell lung cancer (NSCLC) patients. EXPERIMENTAL DESIGN: In this Phase II trial, patients with unresectable stage III NSCLC were treated with the oral administration of UFT (400 mg/m(2)/d tegafur) on days 1-14 and days 29-42 whereas 80 mg/m(2) cisplatin was administered i.v. on days 8 and 36. Radiotherapy, with a total dose of 60 Gy, was delivered in 30 fractions from day 1. RESULTS: Seventy patients were enrolled and eligible, as follows: 57 males/13 females; mean age 61 ranging from 36 to 74; performance status 0/1:45/25; stage IIIA/IIIB, 14/56. A complete response was observed in two patients and a partial response in 54 patients, and the overall response rate was 81% (95% confidence interval; 70-89%). The median survival, the 1- and 2-year survival rates were 16.5 months, 67% and 33%, respectively. Grade 3/4 leukopenia occurred in 14%/1% of the patients. Grades 3 non-hematological toxicities were only reported in three patients with nausea, two with esophagitis and one with pneumonitis whereas no grade 4 non-hematological toxicity was observed. CONCLUSIONS: UFT plus cisplatin with concurrent radiotherapy is considered to be a feasible and effective treatment for locally advanced NSCLC patients. Additional study of this concurrent chemoradiotherapy is warranted.     

Multicenter phase II trial of paclitaxel, cisplatin, and etoposide with concurrent radiation for limited-stage small-cell lung cancer.

PURPOSE: To investigate the feasibility, efficacy, and safety of adding paclitaxel to cisplatin/etoposide chemotherapy and concurrent thoracic radiotherapy (TRT) in treatment of limited-stage small-cell lung cancer (LD-SCLC). PATIENTS AND METHODS: Patients received five courses of chemotherapy (paclitaxel 175 mg/m2 1-hour intravenous [IV] infusion day 1; cisplatin 50 mg/m(2) IV day 1; etoposide 100 mg/m2 IV day 1; oral etoposide 100 mg bid days 2 to 5) at 3-week intervals. TRT (42 Gy administered in 15 fractions) was administered concurrent with chemotherapy cycle 3. All patients were evaluated before starting TRT and 4 weeks after termination of chemotherapy. Patients achieving complete remission (CR) were administered prophylactic cranial irradiation. RESULTS: Thirty-nine patients were included, and the median age was 63 years. The median follow-up was 36 months (range, 19 to 57 months). The overall response rate was 92% (CR, 81%; partial response, 11%), and the median survival was 21 months. The 1- and 2-year disease-specific survival rates were 69% and 37%, respectively. Of 29 CR patients, 83% have relapsed. Brain metastasis was as frequent as local recurrences (42%). Hematologic toxicity included grade 3 to 4 leukopenia in 74% of patients and grade 3 thrombocytopenia in 10%. One treatment-related death occurred as a result of severe neutropenia and septicemia. Hematotoxicity caused dose reductions in 31% of courses. One patient had an anaphylactic reaction during the first paclitaxel infusion. Paclitaxel-related neuropathy and myalgia were reversible. Grade 3 esophagitis was seen in five patients during and shortly after TRT. CONCLUSION: This novel multimodal regimen is effective and well tolerated in patients with LD-SCLC. It compares favorably with previously published phase II studies.     

Concurrent chemoradiotherapy for squamous cell carcinoma of thoracic esophagus: feasibility and outcome of large regional field and high-dose external beam boost irradiation

OBJECTIVE: To assess the feasibility and outcome of concurrent chemoradiotherapy (CT-RT) with large regional field and high-dose external beam boost irradiation in thoracic esophageal cancer. METHODS: Patients with clinical stage T1 (submucosal)-4N0-1M0 (UICC 1997) squamous cell carcinoma of the thoracic esophagus were eligible. Radiotherapy consisted of regional irradiation (extending from supraclavicular fossa to the paracardial area) with 39.6 Gy followed by high-dose external beam boost up to 66.6 Gy (1.8 Gy/day, five times per week). Two-hour infusion of cisplatin (80 mg/m(2) on day 1) and continuous infusion of 5-fluorouracil (800 mg/m(2)/day on days 2-6) were administered concurrently with radiotherapy, every 3-4 weeks, for two cycles. RESULTS: Thirty patients (stage I, 3; stage II, 11; stage III, 16) were entered into the study. Twenty-one patients (70%) completed the planned treatment. In elderly (> or = 70 years) patients, four of six withdrew. Grade 3 and 4 toxicities (NCI-CTC) were observed in 20 (67%) and three (10%) patients, respectively. Major toxicities were blood, gastrointestinal (i.e. nausea and esophagitis) and pulmonary. There was no grade 5 (fatal) toxicity. The median follow-up period for surviving patients was 27 months (range: 9-49 months). The median survival time was 21 months. The 1- and 2-year survival rates were 65 and 49% for all 30 patients. The incidence of esophageal stricture (grade 1-2: RTOG) was 21%. No patient suffered fistula formation. CONCLUSIONS: Despite poor compliance for elderly patients and frequent severe toxicities, our concurrent CT-RT resulted in a favorable outcome in thoracic esophageal cancer.     

食管癌术后局部复发的立体适形放疗疗效分析

目的　评价立体适形放射治疗食管癌术后局部复发灶的近期疗效。方法　 2 0 0 0年 1月至 2 0 0 2年 12月间收治的 2 5例食管癌术后纵隔瘤床区复发或纵隔加吻合口复发病例 ,采用CT模拟定位技术和立体适形放疗技术 ,PTV为CTV外放 1 0cm ,采用 5～ 7个非共面野照射 ,用剂量体积直方图和等剂量线优化治疗计划 ,15MVX线 ,单次剂量 3Gy ,每周 5次 ,总剂量 60～ 66Gy ,PTV被 85 %等剂量线所包绕 ,PTV均匀性为 95 %～ 10 7%。结果　近期疗效为CR 4例 ,PR 2 1例 ,总有效率为 10 0 %。1、2年生存率及 1年局控率分别为 72 %、3 2 %、88%。按RTOG标准评价 :急性放射性食管炎Ⅰ～Ⅱ级 6例 (2 4% ) ,Ⅲ级 1例 (4 % ) ,急性放射性肺炎Ⅰ～Ⅱ级 8例(3 2 % ) ,Ⅲ级 1例 (4 % ) ,骨髓抑制Ⅰ～Ⅱ级 4例 (16% ) ,急性心脏损伤Ⅰ～Ⅱ级 2例 (8% )。结论　立体适形放射治疗能有效提高食管癌术后局部复发灶的局部控制率 ,改善临床症状 ,延长生存期 ,是局部剂量升级的有效方法 ,能提高生存质量 ,近期疗效满意。     

Combined chemotherapy with twice-daily radiation therapy for inoperable squamous cell carcinoma of the thoracic esophagus

Background A study with chemotherapy and twice-a-day radiotherapy in patients with esophageal carcinoma was performed to evaluate toxicity and efficacy. Methods Thirty-seven patients with squamous cell carcinoma of the thoracic esophagus (1, stage IIB; 19, stage III; 17, stage IV) were enrolled. The chemotherapy regimen consisted of 3 cycles with cisplatin (70 mg/m² on day 1) and 96-hour continuous infusion 5-fluorouracil (700 mg/m² per day on days 1 to 4). Second and third cycles were initiated on day 22 and day 92, respectively. Radiotherapy was administered twice daily with concomitant boost technique over days 43 to 75, up to a total dose of 60 Gy. Daily fractions were 2.0 Gy for large fields and 1.0 Gy for small fields at 4- to 6-hour intervals. Results Twenty-nine patients (78%) received the full treatment. Of the 36 patients who started radiotherapy, 94% were able to complete the full course. Grade 3+toxicities observed were leukopenia 5%, anemia 14%, thrombocytopenia 5%, vomiting 14%, esophagitis 5%, pulmonary toxicity 5%, cardiac toxicity 3%, hepatic dysfunction 3%, and nephrotoxicity 3%. Of the 36 patients who started radiotherapy, 8 (22%) showed complete response, and 16 (44%) had partial response. The median survival time was 9 months, with a 1-year actuarial survival rate of 33%. Death was due to local-regional tumor manifestations in 18 patients. Conclusion The preliminary analysis showed that this treatment scheme was well tolerated with acceptable toxicity, but local-regional failure remains the principal cause of death. New treatment schemes such as concurrent use of chemotherapy with radiation warrant further investigation.     

Dosimetric correlations of acute esophagitis in lung cancer patients treated with radiotherapy

PURPOSE: To evaluate the factors associated with acute esophagitis in lung cancer patients treated with thoracic radiotherapy. METHODS AND MATERIALS: We examined 35 patients with non-small-cell lung cancer (n = 27, 77%) and small-cell lung cancer (n = 8, 23%) treated with thoracic radiotherapy between February 2003 and November 2004. The median patient age was 70 years (range, 50-83 years). The disease stage was Stage I in 2 patients (6%), Stage II in 1 (3%), Stage IIIa in 10 (28%), Stage IIIb in 9 (26%), and Stage IV in 9 (26%); 4 patients (11%) had recurrent disease after surgery. A median dose of 60 Gy (range, 50-67 Gy) was given to the isocenter and delivered in single daily fractions of 1.8 or 2 Gy. With heterogeneity corrections, the median given dose to the isocenter was 60.3 Gy (range, 49.9-67.2 Gy). Of the 35 patients, 30 (86%) received concurrent chemotherapy consisting of a platinum agent, cisplatin or carboplatin, combined with paclitaxel in 18 patients (52%), irinotecan hydrochloride in 7 (20%), vincristine sulfate and etoposide in 2 (5%), vinorelbine ditartrate in 1 (3%), etoposide in 1 (3%), and docetaxel in 1 patient (3%). Three of these patients underwent induction therapy with cisplatin and irinotecan hydrochloride, administered before thoracic radiotherapy, and concurrent chemotherapy. Esophageal toxicity was graded according to the Radiation Therapy Oncology Group criteria. The following factors were analyzed with respect to their association with Grade 1 or worse esophagitis by univariate and multivariate analyses: age, gender, concurrent chemotherapy, chemotherapeutic agents, maximal esophageal dose, mean esophageal dose, and percentage of esophageal volume receiving >10 to >65 Gy in 5-Gy increments. RESULTS: Of the 35 patients, 25 (71%) developed acute esophagitis, with Grade 1 in 20 (57%) and Grade 2 in 5 (14%). None of the patients had Grade 3 or worse toxicity. The most significant correlation was between esophagitis and percentage of esophageal volume receiving >35 Gy on univariate (p = 0.002) and multivariate (p = 0.018) analyses. CONCLUSION: The percentage of esophageal volume receiving >35 Gy was the most statistically significant factor associated with mild acute esophagitis.     

The safety and usefulness of high-dose-rate endoluminal brachytherapy as a boost in the treatment of patients with esophageal cancer with external beam radiation with or without chemotherapy

PURPOSE: This study reports the results of a single-institution experience with high-dose-rate brachytherapy (HDRBT) used as a boost in the treatment of esophageal cancer with external beam radiation therapy (ERT) with or without chemotherapy. METHODS AND MATERIALS: Patients without evidence of metastatic disease were identified. HDRBT was given before ERT with a dose of 20 Gy in 5 fractions. Patients with a Karnofsky performance of more than 70 received treatment with 50 Gy in 25 fractions and concurrent 5-fluorouracil and cis-platinum during Weeks 1 and 5, whereas patients with a Karnofsky performance of less than 70 were treated with radiation therapy alone with 35 Gy in 14 fractions. RESULTS: Fifty-three patients received HDRBT treatment with combined ERT and chemotherapy and 17 patients with ERT alone. The incidence of acute bone marrow toxicity was 55% Grade 2 and 15% Grade 3, and 85% of patients had Grade 2 esophagitis. With a median follow-up time of 26 months, the median survival was 21 months; the 2-year local recurrence was 25%, and the 5-year survival rate was 28%. CONCLUSION: HDRBT is safe and beneficial for local control in the radical treatment of patients with esophageal cancer.     

Hyperfractionated accelerated radiotherapy (HART) for inoperable, nonmetastatic non-small cell lung carcinoma of the lung (NSCLC): results of a phase II study for patients ineligible for combination radiochemotherapy

Purpose: To evaluate a hyperfractionated and accelerated radiotherapy (HART) protocol in patients with inoperable non-small cell lung carcinoma (NSCLC) who were ineligible for combination radiochemotherapy studies.

Methods and Materials: From February 1989 through August 1994, 23 patients ineligible for available combined modality protocols in our institution were enrolled and treated with HART, consisting of 63 Gy given in 42 fractions of 1.5 Gy each, twice daily, with a minimum time interval of 6 h between fractions, 5 days a week, over an elapsed time of 4.2 weeks, or 29 days. There was no planned interruption.

Results: The 1-, 2-, and 3-year survival rates were 61%, 39%, and 19%, respectively, with a median survival of 16.8 months. At the time of analysis, 4 patients are alive and 19 have died, 16 from NSCLC and 3 from cardiac disease. Overall response rate was 48%, with 22% of patients achieving a complete response and 26% a partial response. Correlation between acute response rate and survival was poor. First site of relapse was local-regional in 8 patients (35%), distant in 6 patients (26%), and local-regional and distant in 4 (17%) patients. One patient had Grade IV and 2 had Grade III esophagitis. One patient presented with chronic Grade III lung toxicity. There were no treatment-related deaths.

Conclusion: In this group of 23 patients ineligible for radiochemotherapy, this HART regime was quite feasible and was followed by little toxicity. Results in this particularly poor prognosis NSCLC patient category should be compared to series with a similar patient profile; however, median survival is at least similar to that obtained in recent series of combination radiochemotherapy.     

Induction and concurrent paclitaxel/carboplatin every 3 weeks with thoracic radiotherapy in locally advanced non-small-cell lung cancer: an interim report

The paclitaxel/carboplatin combination has demonstrated promising activity in metastatic non-small-cell lung cancer (NSCLC); therefore, we mounted an exploratory study of these agents with thoracic radiation (TRT) in locally advanced NSCLC. Eligibility stipulated a Karnofsky performance status >or= 70%, weight loss or= 2 esophagitis has corresponded to length (> 16 cm) of esophagus in the radiation treatment field (Fisher's exact test, P = 0.006). The partial response rate to induction therapy was 40% and to the combined modality therapy was 60%. The median survival for all 49 patients is 15.3 months, with a median disease-free survival (DFS) of 7.8 months. In the subset of 22 patients treated on the phase I portion of the study, the median survival and DFS were 18.5 months and 13.5 months, respectively. Induction therapy with paclitaxel and carboplatin followed by concurrent chemoradiotherapy with the same agents is an active and well-tolerated treatment approach in locally advanced NSCLC. To date, paclitaxel 175 mg/m2 plus carboplatin AUC 5 administered at 3-week intervals for 2 cycles is safe in combination with TRT.