Concomitant boost radiation therapy for inoperable non-small-cell lung cancer: preliminary report of a prospective randomized study

PURPOSE: The radiation therapy results for patients with inoperable non-small-cell lung cancer (NSCLC) have been disappointing. Tumor dose escalation using concomitant boost technique (CBT) has been shown to improve local control in a few prospective studies. This trial was carried out to prospectively assess the radiation response and acute toxicity of CBT in comparison to the conventional treatment technique (CTT). METHODS AND MATERIALS: Ninety-seven consecutive eligible patients were entered in this prospective clinical trial between November 1994 and February 1998. Patients were randomized to receive either CBT (43 patients) or CTT (54 patients) radiation therapy. These patients either refused chemotherapy or were judged as unsuitable for chemotherapy. Patients in the CBT group received 46.8 Gy in 26 fractions using large fields that encompassed the gross and occult disease. A concomitant boost of 18.2 Gy (0.7 Gy per fraction) was delivered to the gross disease using small fields with 1.5-cm margins. The small fields were treated concurrently with the large fields and the total dose to the tumor area was 65 Gy in 26 fractions. Patients in the CTT group received 70.8 Gy in 38 fractions. The acute toxicity between each group was compared. The response rate was analyzed and compared by treatment group, gender, age, stage, histology, initial Karnofsky performance score (KPS), severity of acute toxicity, and maximum body weight loss (MBWL) during treatment course. RESULTS: The demographic parameters such as sex, age, and stage were evenly distributed in each treatment group. The majority of these patients had Stage IIIA and IIIB disease. Overall median treatment times were 39 days for the CBT group of patients and 62 days for the CTT group. No treatment-related mortality was found. There were 2 patients in the CTT group with acute RTOG Grade 3 lung toxicity, and no Grade 3 lung or esophageal toxicity was observed in CBT group. The response rates, assessed by radiographic images, were 69.8% and 48.1% for the CBT and CTT patients, respectively. Univariate and multivariate analysis revealed that patients in the CBT group, patients with better KPS, and patients with more severe acute toxicity had a higher response rate. CONCLUSION: This study demonstrates that concomitant boost radiation therapy is tolerable, and produces a superior response rate than conventional radiation therapy for patients with inoperable NSCLC. The length of treatment was reduced from 38 to 26 treatment days, almost a 30% reduction.     

RTOG 96-10: reirradiation with concurrent hydroxyurea and 5-fluorouracil in patients with squamous cell cancer of the head and neck

Purpose: Patients with recurrent squamous cell cancer of the head and neck (SCH&N) are generally treated with systemic chemotherapy. Improvement in survival has not occurred, despite an increased objective response rate. This study was undertaken to explore the feasibility and toxicity, and estimate the therapeutic impact of, reirradiation (RRT) with concurrent hydroxyurea and 5-fluorouracil.

Methods and Materials: The eligibility requirements included SCH&N presenting as a second primary or recurrence ≥6 months after definitive RT to ≥45 Gy, with ≥75% of the tumor volume within the previous field. The cumulative spinal cord dose was limited to 50 Gy, and measurable disease was required. Four weekly cycles were given, each separated by 1 week of rest. A cycle consisted of 5 days, Monday through Friday, of 1.5-Gy twice-daily repeated RT, with the fractions separated by ≥6 h, with 1.5 g of hydroxyurea given 2 h and 300 mg/m² of a 5-fluorouracil IV bolus given 30 min before each second daily fraction.

Results: Eighty-six patients were entered; 81 patients were assessable. The median prior radiation dose was 61.2 Gy. The 4 planned cycles were delivered in 79% of patients. Grade 3 mucositis occurred in 14% of patients, and Grade 4 in 5%. Grade 3 acute pharyngeal toxicity was seen in 17%. Grade 3 neutropenia occurred in 9%, Grade 4 in 10%, and Grade 5 in 7%. Six patients died of treatment-related toxicity. Two died of hemorrhage from the tumor site without thrombocytopenia. With a median follow-up of 16.3 months for living patients, the estimated median overall survival was 8.2 months and the estimated 1-year survival rate 41.7%. Patients treated >3 years after the previous RT had a 1-year survival rate of 48% compared with 35% for patients treated within 3 years (p = 0.017). The 1-year survival rate for patients with a second primary was 54% compared with 38% for patients with recurrence (p = 0.083).

Conclusion: Repeated RT with concurrent chemotherapy as given in this study is a feasible approach for selected, previously irradiated patients with SCH&N and may produce increased median and 1-year survival rates compared with systemic chemotherapy trials reported in the literature. A randomized study should be conducted to compare these two different approaches.     

后程加速超分割适形放疗同步化疗治疗食管癌的临床观察

目的:观察后程加速超分割适形放疗同步化疗治疗食管癌临床疗效。方法:69例患者随机分为两组:后加组(后程加速超分割适形放疗同步化疗组)35例和对照组(常规分割放疗同步化疗组)34例。采用6/15MVX线外照射,后加组常规分割放疗40Gy/20次后改为2次/d,间隔>6h,1.4Gy/次,总剂量为65.2Gy/38次。对照组2Gy/次,5次/周,总剂量60～66Gy。两组均从放疗第1天开始化疗,化疗方案如下:顺铂(DDP)20mg,替加氟1.0g,甲酰四氢叶酸钙(CF)0.2g,均静脉滴入,d1～d5,21d为1个周期。结果:后加组与对照组1年局部控制率分别为85.7%(30/35)和64.7%(22/34),P=0.043;后加组1年总生存率及疾病无进展生存率分别为77.2%和52.9%,对照组分别为71.5%和47.1%,P值分别为0.035和0.039;后加组2年预期生存率和疾病无进展生存率分别为68.9%和44.2%,对照组分别为60.0%和35.3%,P值分别为0.039和0.040。后加组Ⅱ、Ⅲ级急性放射性食管炎发生率分别为8.6%(3/35)和5.7%(2/35),对照组分别为8.8%(3/34)和5.9%(2/34);后加组Ⅱ、Ⅲ级急性放射性肺炎发生率分别为2.9%(1/35)和0,对照组分别为5.9%(2/34)和2.9%(1/34)。结论:与对照组相比,后程加速超分割适形放疗同步化疗治疗食管癌明显提高了患者的近期疗效及局部控制率,且正常组织的放射性损伤未明显增加。     

改良同步后程加速超分割放化疗治疗局部晚期食管鳞癌的临床观察

 目的 探讨改良同步后程加速超分割放疗联合含铂类方案的化疗治疗局部晚期食管鳞癌的疗效和不良反应.方法 68例经病理证实的食管鳞癌患者入组。先行常规分割放疗40 Gy/20次后改行加速超分割放疗1.4 Gy/次,2次/d,间隔≥6 h,照射14次,总剂量59.6 Gy。同步给予以顺铂为基础的联合化疗2个周期,同步放化疗结束后再行2周期化疗。观察患者近期疗效,1、3、5年生存率及治疗相关不良反应。结果 所有患者完成放疗计划,总有效率为91.6%（62/68）。1、3、5年生存率分别为75.5%、46.5%、22.7%。≥3级放射性食管炎的发生率为26.4%;无3级及以上的放射性肺炎发生;放射性皮肤损伤多为0~1级;3级白细胞减少和血小板减少的发生率分别为29.4%和7.4%,4级白细胞减少和血小板减少的发生率均为2.9%。无食管狭窄及严重的肺纤维化发生,有2例（2.9%）出现食管纵隔瘘。结论 改良同步后程加速超分割放化疗治疗局部晚期食管鳞癌疗效满意,治疗相关不良反应发生率降低。     

Clinical results of radiation therapy for stage I esophageal cancer: a single institutional experience

From 1992 through 2001, 29 patients with stage I esophageal cancer were treated with radiation therapy. All patients had squamous cell carcinoma. Seventeen patients were treated with radiotherapy alone, and 12 were treated with a combination of chemotherapy and radiotherapy. Most of the chemotherapy regimens included cisplatin and/or 5-fluorouracil (5-FU). Twelve patients were treated with intracavitary irradiation (low-dose rate: 6, high-dose rate: 6) after external radiotherapy. Median fraction and total doses of external radiotherapy given were 2.0 Gy and 60.6 Gy, respectively. Median doses of intracavitary irradiation were 18 Gy/6 fractions in low-dose-rate brachytherapy and 13.5 Gy/4.5 fractions in high-dose-rate brachytherapy. The 5-year overall survival rate was 62%. The 5-year local control rate was 44%. Of the 29 patients, 9 had in-field recurrence in the esophagus and 1 had recurrence in the esophagus outside of the irradiated field. Of 9 patients with in-field local recurrence, 1 also developed mediastinal lymph node metastases and 1 had distant metastasis. Radiation therapy is an effective treatment modality for stage I esophageal cancer.     

Dose-volumetric parameters of acute esophageal toxicity in patients with lung cancer treated with three-dimensional conformal radiotherapy

PURPOSE: To retrospectively evaluate which dose-volumetric parameters are associated with the risk of > or = Grade 3 acute esophageal toxicity (AET) in lung cancer patients treated with three-dimensional conformal radiotherapy (3D-CRT). METHODS AND MATERIALS: One hundred twenty-four lung cancer patients treated curatively with 3D-CRT were retrospectively analyzed. All patients received conventionally fractionated radiotherapy (RT) with median dose of 60 Gy (range, 54-66 Gy) delivered in 30 fractions (range, 27-33 fractions). Thirty-one patients underwent curative surgery before RT. Ninety-two patients received chemotherapy (induction, 18; concurrent +/- induction, 74). Acute esophageal toxicity was scored by Radiation Therapy Oncology Group criteria. The parameters analyzed included sex; age; Karnofsky performance score; weight loss; surgery; concurrent chemotherapy; the percentages of organ volume receiving > or =20 Gy (V20), > or =30 Gy (V30), > or =40 Gy (V40), > or =50 Gy (V50), > or =55 Gy (V55), > or = 58 Gy (V58), > or =60 Gy (V60), and > or =63 Gy (V63); the percent and absolute length of the esophagus irradiated; the maximum and mean dose to the esophagus; and normal tissue complication probability. RESULTS: Of the 124 patients, 15 patients (12.1%) had Grade 3 AET, and 1 (0.8%) patient had Grade 4 AET. There was no fatal Grade 5 AET. In univariate and multivariate logistic regression analyses, concurrent chemotherapy and V60 were significantly associated with the development of severe (> or = Grade 3) AET (p < 0.05). Severe AET was observed in 15 of 74 patients (20.3%) who received concurrent chemotherapy, and in 1 of 50 patients (2.0%) who did not (p = 0.002). Severe AET was observed in 5 of 87 patients (5.7%) with V60 < or = 30% and in 11 of 37 patients (29.7%) with V60 > 30% (p < 0.001). Among 50 patients who did not receive concurrent chemotherapy, severe AET was observed in 0 of 43 patients (0%) with V60 < or = 30% and in 1 of 7 patients (14.2%) with V60 > 30% (p = 0.140). Among 74 patients who received concurrent chemotherapy, severe AET was observed in 5 of 44 patients (11.4%) with V60 < or = 30% and in 10 of 30 patients (33.3%) with V60 > 30% (p = 0.037). CONCLUSIONS: Concurrent chemotherapy and V60 were associated with the development of severe AET > or = Grade 3. For patients being treated with concurrent chemotherapy, V60 is considered to be a useful parameter predicting the risk of severe AET after conventionally fractionated 3D-CRT for lung cancer.     

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.     

Twice-daily reirradiation for recurrent and second primary head-and-neck cancer with gemcitabine, paclitaxel, and 5-fluorouracil chemotherapy

PURPOSE: We previously demonstrated the efficacy of concurrent gemcitabine, paclitaxel, and 5-fluorouracil in conjunction with twice-daily (1.5-Gy) radiotherapy delivered on alternating weeks (TFGX(2)) in locally advanced head-and-neck cancer. Here, we report the clinical outcome and late toxicity of TFGX(2) in a subset of patients previously irradiated to the head and neck. METHODS AND MATERIALS: Twenty-nine previously irradiated patients, presenting with recurrent or second primary head-and-neck cancer, underwent TFGX(2). Twelve patients underwent attempted surgical resection before chemoradiotherapy, 10 of whom were left with no measurable disease. Patients with measurable disease received a median radiation dose of 72 Gy; those with no measurable disease received a median dose of 61 Gy. The cumulative dose ranged from 74.4 to 156.4 Gy (mean, 125.7 Gy; median, 131.0 Gy). RESULTS: The median follow-up was 19.1 months (50.9 months for living patients). The 5-year overall survival rate was 34.5%, and the locoregional control rate was 54.5%. In patients with measurable disease at treatment, the 5-year overall survival and locoregional control rate was 26.3% and 45.1%, respectively, compared with 50.0% (p = 0.14) and 70% (p = 0.31), respectively, for those with no measurable disease. Measurable disease and radiation dose were highly statistically significant for overall survival and locoregional control on multivariate analysis. Of 14 patients assessable for late toxicity, 3 developed Grade 4-5, 8 Grade 2-3, and 3 Grade 0-1 toxicity. CONCLUSION: Aggressive reirradiation with chemotherapy in locally advanced head-and-neck cancer provides a chance for long-term cure at the expense of toxicity. Attempted surgical resection before chemoradiotherapy improved disease control and survival.     

Routine use of approximately 60 Gy once-daily thoracic irradiation for patients with limited-stage small-cell lung cancer

PURPOSE: To review the outcome of patients with limited-stage small-cell lung cancer receiving daily thoracic irradiation (RT) to approximately 60 Gy. METHODS AND MATERIALS: The records of patients treated with RT for limited-stage small-cell lung cancer between 1991 and 1999 at Duke University were retrospectively reviewed. Sixty-five patients were identified who had received continuous course once-daily 1.8-2 Gy fractions to approximately 60 Gy (range 58-66). All patients received chemotherapy (CHT); 32 received concurrent RT/CHT and 33 sequential CHT and then RT. Prophylactic cranial RT was administered to 17 patients. The time from diagnosis to local failure, tumor progression, and death was assessed using actuarial methods. The median follow-up for all patients was 16.7 months and for surviving patients was 29.6 months. The median age was 64 years (range 36-83), and the median Karnofsky performance status was 80 (range 50-100). RESULTS: The 3-year actuarial rate of local failure, progression-free survival, and overall survival was 40%, 25%, and 23%, respectively. One case of acute Grade 3 esophagitis developed. Ten late complications occurred: four pulmonary, two esophageal, two infectious, one leukemia, and one retinal toxicity with prophylactic cranial RT. Six were mild and resolved with treatment. CONCLUSION:CHT plus approximately 60 Gy of once-daily RT for limited-stage small-cell lung cancer was generally well tolerated. The survival rates were less than have been reported using 45 Gy in 1.5-Gy twice-daily fractions (2-year overall survival rate 47% compared with 30% in this study), but may be comparable because fewer than one-half our patients received concurrent CHT/RT and only 26% received prophylactic cranial RT. The relatively low rate of normal tissue morbidity in our patients supports the use of conventional once-daily fractionation to > or = 60 Gy. A randomized trial would be required to compare the outcomes after maximally tolerated dose twice-daily RT vs. maximally tolerated dose daily RT.     

同步放化疗治疗食管癌纵隔转移的临床疗效分析

目的探讨放化疗同步治疗食管癌纵隔淋巴结转移的临床疗效。方法将76例食管癌治疗后发生纵隔淋巴结转移的患者随机分为两组,观察组(同步放化疗组)36例和对照组(单纯放疗组)40例。观察组采用FD方案化疗,同时给予三维适形放射治疗,2.5~3.5Gy/次,5次/周,照射总剂量60~68 Gy。对照组采用单纯放射治疗,放疗方法同观察组。结果治疗后1个月复查,观察组CR 26例,PR 10例;对照组CR 19例,PR 19例,无进展病例。观察组和对照组1,2,3年生存率分别为88.9%、55.6%、27.8%和82.5%、37.5%、15.0%。结论同步放化疗治疗食管癌纵隔淋巴结转移,疗效优于单纯放疗,能提高生存期。     

Two fractions of high-dose-rate brachytherapy in the management of cervix cancer: clinical experience with and without chemotherapy

PURPOSE: In recent years, high-dose-rate brachytherapy has become popular in the management of carcinoma of the uterine cervix, because it eliminates many of the problems associated with low-dose-rate brachytherapy. However, the optimum time-dose-fractionation remains controversial. Two fractions of high-dose-rate brachytherapy are convenient for patients, but most radiation oncologists in the United States do not use them, because of fear that they could lead to excessive rectal or bladder toxicity. Here we present our experience, which suggests that a two-fraction regimen is indeed safe and effective. METHODS: We treated 49 patients with Stages I-III biopsy-proven carcinoma of the uterine cervix by external beam radiation therapy (EBRT), plus two fractions of high-dose-rate brachytherapy. The histology was squamous cell carcinoma in 43 patients (88%) and nonsquamous in 6 (12%). The median size of the primary tumor was 6 cm (range: 3-10 cm). Each patient received EBRT to the pelvis to a median dose of 45 Gy (range: 41.4-50.4 Gy), followed by a parametrial boost when indicated. Thirty patients (61%) also received irradiation to the para-aortic lymph nodes to a dose of 45 Gy. After EBRT, each patient underwent two applications of high-dose-rate brachytherapy, 1 week apart. The dose delivered to point A was 9 Gy per application for 49 applications (50%) and 9.4 Gy for 43 applications (44%), and it varied from 7 to 11 Gy for the rest (6%). The total dose to the rectum from both high-dose-rate brachytherapy applications ranged from 4.7 to 11.7 Gy (median: 7.1 Gy), and the total dose to the bladder from 3.8 to 15.5 Gy (median: 10.5 Gy). Twenty-five of the 49 patients (51%) received concomitant chemotherapy (cisplatin 20 mg/m(2)/day for 5 days) during the first and fourth weeks of EBRT and once after the second high-dose-rate brachytherapy application. Chemotherapy was not assigned in a randomized fashion. The use of chemotherapy increased during the time period spanned by this study as increasing evidence supporting the use of chemotherapy began to appear. RESULTS: The observed survival rates after 2, 3, and 5 years were 83%, 78%, and 78%, respectively. The surviving patients have been followed up for a median of 3 years (range: 2-6 years). Eight of the 49 patients suffered local failures. Among patients treated without chemotherapy, the 3-year local control rate was 77%; it was 88% among those receiving chemotherapy. There have been no regional failures. Four patients developed distant metastases. At 3 years, 91% of the patients in each group were free of distant metastases. Ten of the 49 patients (20%) suffered Grade 3 acute toxicity; 11 (22%) had Grade 4. Among the 24 patients treated without chemotherapy, only 1 (4%) suffered Grade 3 toxicity. Among the 25 patients receiving chemotherapy, in contrast, 8 (32%) suffered Grade 3 and 12 (48%) Grade 4 acute toxicity. Only 2 patients suffered late toxicity: One suffered Grade 2 and the other Grade 3 late toxicity. The actuarial risk of Grade 2 or worse late toxicity was 5%, with or without chemotherapy. CONCLUSIONS: Our experience suggests that two fractions of high-dose-rate brachytherapy are safe and effective in the management of cervix cancer, even in conjunction with concomitant cisplatin. The fears that the use of two fractions would lead to excessive rectal or bladder toxicity proved unfounded. Guidelines for ensuring a low complication rate are discussed.     

Improvement of local control of T3 and T4 nasopharyngeal carcinoma by hyperfractionated radiotherapy and concomitant chemotherapy

PURPOSE: When the primary tumor of nasopharyngeal carcinoma (NPC) is treated at the base of skull and intracranium with conventional radiotherapy, the result is generally poor. In this report, we investigated whether hyperfractionated radiotherapy (HFRT) and concomitant chemotherapy (CCT) could achieve better local control and survival in NPC patients with T3 and T4 lesions. PATIENTS AND METHODS: Forty-eight patients (11 T3 and 37 T4 NPC) were treated with HFRT and CCT. HFRT was administered at 1.2 Gy per fraction, two fractions per day, Monday-Friday for 62 fractions for a total dose of 74.4 Gy. Concomitant chemotherapy consisting of cis-diamino-dichloroplatinum (CDDP) alone or CDDP and 5-fluorouracil was delivered simultaneously with radiotherapy during Weeks 1 and 6. Adjuvant chemotherapy consisted of CDDP and 5-fluorouracil for 2 to 3 cycles and was given monthly beginning 1 month after completion of radiation. RESULTS: With a median follow-up of 57 months (range: 28-94 months), the 3-year locoregional control rate was 93%, the disease-free survival rate was 71%, and the overall survival rate was 72%. For T4 patients, the 3-year locoregional control rate was 91%, disease-free survival was 62%, and overall survival was 63%. The major acute toxicity was Grade 3 mucositis in 73% and Grade 2 weight loss in 31% of patients. Fifty percent of patients were tube fed. Most patients tolerated the combined modality treatments relatively well; 88% of patients completed their radiation treatment within 8 weeks. CONCLUSION: HFRT and CCT for T3 and T4 NPC were associated with excellent local control and improved survival. The treatment-related toxicity was acceptable and reversible. We would recommend using HFRT with CCT for advanced T-stage NPC if the three-dimensional conformal radiation planning shows a significant portion of the brainstem to be inside the treatment field.     

Hyperfractionated radiotherapy for clinical stage II non-small cell lung cancer.

BACKGROUND AND PURPOSE: Patients with stage II non-small cell lung cancer who are not suitable for or refuse surgery are treated with radiotherapy, but the results reported so far are not satisfactory. To improve the prognosis of such patients, we have used hyperfractionated radiotherapy. In this paper, we retrospectively analyzed results of the treatment. MATERIALS AND METHODS: Between 1988 and 1993, 67 patients were treated with hyperfractionated radiotherapy with 1.2 Gy twice daily to a total dose of 69.6 Gy. All patients were technically operable, but 43 had medical problems and 24 refused surgery. The median age and Karnofsky performance status score was 60 and 90 years, respectively. No patient received chemotherapy or immunotherapy. The median follow-up period was 61 months. RESULTS: The median survival time and the 5-year survival rate were 27 months and 25% (standard error, SE, 6%), respectively. The 5-year local control rate was 44% (SE,7%). Univariate analysis of prognostic factors revealed that a higher Karnofsky performance status score, weight loss of < or =5% before treatment, and T1 stage were associated with better prognosis, and peripheral location was of borderline significance (P = 0.053). There were two bronchopulmonary and two esophageal acute grade 3 toxicities, and one bronchopulmonary and two esophageal late grade 3 toxicities. No grade 4 or 5 toxicity was observed. CONCLUSION: These results are encouraging and further studies on the use of hyperfractionation seem to be warranted for stage II non-small cell lung cancer.     

Combined treatment modality for anaplastic oligodendroglioma and oligoastrocytoma: a 10-year update of a phase II study

PURPOSE: To provide updated outcome data (10 years) of a Phase II study of combined surgery, postoperative radiotherapy, and adjuvant chemotherapy in patients with anaplastic oligodendroglioma and oligoastrocytoma. METHODS AND MATERIALS: In 23 adult patients, surgery, postoperative radiotherapy (60 Gy in 30 daily fractions within 6 weeks), and adjuvant modified chemotherapy (procarbazine 60 mg/m(2) on Days 1-14, lomustine 100 mg/m(2) on Day 1, and vincristine 1.4 mg/m(2) [maximum 2 mg] on Days 1 and 8) were administered every 6 weeks for up to six cycles or until progression occurred. RESULTS: The median follow-up was 116 months for all patients. The median survival time was 118 months, and the 5-year and 10-year survival rate was 57% and 47%, respectively. The median time to tumor progression was 78 months, with a 5-year and 10-year progression-free survival rate of 52% and 39%, respectively. Gender, age, Karnofsky performance status, location, and histologic type did not influence survival. Patients with tumors 4 cm (p = 0.0470), as did those with total tumor resection compared with those with subtotal tumor resection or biopsy only (p = 0.0024). Gender, Karnofsky performance status, location, and histologic type did not influence progression-free survival, but younger age (p = 0.0389), smaller tumor size (p = 0.0357), and more radical surgery (p = 0.0033) correlated positively with it. Acute high-grade (Grade 3 or worse) chemotherapy-related toxicity was mainly hematologic, with 3 patients (13%) experiencing acute Grade 4 toxicity. CONCLUSION: The results of this 10-year update confirmed that the trimodality approach is effective in patients with anaplastic oligodendroglioma and oligoastrocytoma.     

食管癌后程加速超分割照射剂量学研究

目的探讨食管癌后程加速超分割照射剂量并观察两组的近期疗效、局部控制率、放疗耐受性及副反应，并随访其长期生存率。方法采用随机抽签法将100例食管癌随机均分为60Gy组和75Gy组。60Gy组前3周采用常规分割照射，第4周起改用超分割照射（1．5Gy／次，2次／d，2次间隔6h，10次／周），DT60Gy分35次，5周完成。75Gy组照射方法完全相同，前3周常规分割，第4周起改用超分割照射，DT75Gy，分45次，6周完成。结果两组近期疗效无差别，75Gy组无C级。1、3、5年局部控制率60Gy组分别为86％、42％、32％，75Gy组分别为88％、52％、48％；1、3、5年生存率60Gy组分别为86％、40％、28％，75Gy组分别为72％、34％、16％；两组比较均无差别。中位生存期60Gy组25个月，75Gy组19个月。75Gy组重度放射性食管炎明显高于60Gy组（28％：10％，P=0．022），但75Gy组与60Gy组死亡原因无差别。结论食管癌后程加速超分割照射不宜追求高剂量，在照射野及照射技术不变的情况下增加剂量，副反应加大。在考虑增加照射剂量时应充分考虑肺及其他正常组织的量照体积及受照剂苗。     

同步整合加量调强放疗治疗颈及胸上段食管癌的临床观察

目的:观察同步整合加量调强放疗技术(SIB-IMRT)与常规调强放疗技术(IMRT)治疗颈及胸上段食管癌的不良反应及临床疗效.方法:颈及胸上段食管癌患者62例,随机分为SIB-IMRT组及常规IMRT组,同步给予单药顺铂同步化疗.处方剂量:SIB-IMRT组:PGTVnx 66Gy/(2.2Gy·30次),PGTVnd 66Gy/(2.2Gy·30次),PTV 54Gy/(1.8Gy·30次).IMRT组:95%PTV 60Gy/(2.0Gy·30次).结果:SIB-IMRT组1、2年的局部控制率(81.8%、64.5%)较IMRT组1、2年的局部控制率(73.5%、52.7%)提高(P<0.05).SIB-IMRT组1、2年的生存率(77.4%、50.7%)与IMRT组1、2年生存率(74.2%、50.1%)相比,两组差别无统计学意义(P＞0.05).两组患者放射性气管炎和血液学毒性的发生率差异无统计学意义(P＞0.05),SIB-IMRT组放射性肺炎、放射性食管炎的发生率较IMRT组降低(P<0.05).结论:SIB-IMRT治疗颈段及胸上段食管癌,有可能成为提高肿瘤剂量从而提高肿瘤局部控制率、延长患者生存的首选放疗方式.     

Prospective trial of concurrent chemoradiotherapy with protracted infusion of 5-fluorouracil and cisplatin for T4 esophageal cancer with or without fistula

PURPOSE: A prospective trial of concurrent chemoradiotherapy (CT-RT) with a protracted infusion of 5-fluorouracil and cisplatin was performed to evaluate the safety and efficacy of this protocol for T4 esophageal cancer (UICC 1997). METHODS AND MATERIALS: Between 1998 and 2000, 28 patients with T4 esophageal squamous cell carcinomas were treated with concurrent CT-RT. Of the 28 patients, 15 had Stage III, 5 Stage IVA, and 8 Stage IV disease. Five of the T4 tumors had evidence of fistula before treatment. Patients received a protracted infusion of 5-fluorouracil 300 mg/m(2)/24 h on Days 1-14, a 1-h infusion of cisplatin 10 mg/body on Days 1-5 and 8-12, and concurrent radiation at a dose of 30 Gy in 15 fractions during 3 weeks. This schedule was repeated twice, with a 1-week split, for a total RT dose of 60 Gy during 7 weeks for 25 patients. For the remaining 3 patients, 30 Gy of preoperative CT-RT was administered. RESULTS: Of the 25 patients who were treated with the full dose of CT-RT, 14 (56%) completed the two courses of the CT-RT protocol, and 8 patients (32%) received the full dose of RT but a reduced dose of chemotherapy. Eight (32%) of the 25 tumors showed complete regression. Although Grade 3 hematologic toxicities were frequently noted, Grade 4 or more hematologic toxicities were few. Of the 5 T4 fistulous tumors, 2 demonstrated the disappearance of the fistula after CT-RT. However, the worsening or development of an esophageal fistula was noted in 5 patients. The 2-year survival rate for patients with Stage III was 27%, and the median survival time for those with Stage III and Stage IVA+IV was 12 and 5 months, respectively. CONCLUSION: Despite its significant toxicity for esophageal fistula, this concurrent CT-RT protocol of protracted 5-fluorouracil infusion and cisplatin appears feasible and effective for T4 esophageal cancer with or without fistulas.     

Multiple fraction per day radiation therapy for inoperable esophageal cancer

Experience with a multiple fractions per day radiation therapy program for inoperable esophageal cancer is reported. The treatment program consisted of 3 daily fractions of 1.6 Gy, with a 4 hr interval between fractions, for 5 consecutive days (24 Gy). After a rest period of 2 weeks, a second course of radiation was given with the same dose and fractionation for a total dose of 48 Gy in an overall treatment time of 4 weeks. Thirty-four patients were treated between February 1981 and July 1983. Acute reactions consisted of mild esophagitis noted in 30% of patients. No treatment related complications were reported. Median survival was 7 months and the 2- and 5-year survival rates were 12 and 9%, respectively. Tumor size and Karnofsky performance status were found to be the most important prognostic indicators for prolonged survival. Prompt palliation of symptoms was noted. Thirty-three per cent of patients had complete resolution and 41% had partial improvement of symptoms after completion of treatment. Four patients (12%) obtained complete tumor regression with negative biopsy at endoscopic examination and 2 of them are free of disease at 58 and 64 months. A partial response was reported in 12 patients (35%) for a median duration of 5 months (3-26). Treatment with multiple fractions per day was feasible in patients with esophageal cancer and could be preferred to more conventional fractionations for promptness of palliation and the shorter treatment time. The expected therapeutic gain is discussed.     

Escalated hyperfractionated accelerated radiation therapy for locally advanced non-small cell lung cancer: a clinical phase II trial.

BACKGROUND AND PURPOSE: To evaluate the feasibility, toxicity and the efficacy for locally advanced non-small cell lung cancer (NSCLC) treated with escalated hyperfractionated accelerated radiation therapy (EHART) combined with chemotherapy. PATIENTS AND METHODS: The EHART consisted of irradiation delivered twice per day with >6-h interval and five treatment days per week. In the first and second weeks, 1.2 Gy/fraction b.i.d, was given, and then 1. /fraction b.i.d in the third week; 1.4 Gy/fraction b.i.d in the fourth week; and 1. /fraction b.i.d in the fifth week, respectively. The total tumor dose delivered was 66 Gy/50 fractions/5 weeks. All patients received neoadjuvant and adjuvant chemotherapy. The chemotherapeutic regimen used was either MVP (mitomycin C, vindesine, cis-platinum), or EP (etoposide and cis-platinum). RESULTS: From February 1997 to February 1999, 73 eligible patients were registered. All were in stage IIIb with median age of 60 years (33-70). Of the 73 patients, 12 cases were withdrawn from the study due to Grade (Gr) III acute complications, distant metastases, or intercurrent diseases. Sixty-one patients completed the combined treatment as planned. A median of 4 cycles of chemotherapy (1-7) was administered and 66 Gy/50 fractions/36 days was delivered finally. The most common acute complication was radiation esophagitis, which occurred in 56 cases (77%), with Gr III in 11 cases (15%). Twenty-nine patients (40%) had acute pulmonary toxicity; with Gr III in 6 cases (8%). The median survival time was 13 months for the entire group. The 1-year and 2-year survival rates were 51 and 10%, respectively. Of the 61 patients who finished EHART, 34 were found to have locoregional progression. Thirty-two patients failed inside radiation fields, and 2 patients, outside radiation fields. The 1-year and 2-year locoregional progression-free rates were 71 and 34%, respectively. The 1-year and 2-year distant metastasis rates were 57 and 84%, respectively. CONCLUSIONS: EHART combined with chemotherapy could be tolerated by most of the stage IIIb NSCLC patients with acceptable complications. Locoregional control was improved, but the long survival was not prolonged significantly predominantly due to distant metastases.