High-dose conformal radiotherapy for treatment of stage IIIA/IIIB non-small-cell lung cancer: technical issues and results of a phase I/II trial

PURPOSE: We completed a Phase I/II clinical trial (Lineberger Comprehensive Cancer Center 9603), in which we treated 62 Stage IIIA/IIIB inoperable non-small-cell lung cancer (NSCLC) patients with two cycles of induction carboplatin/paclitaxel chemotherapy, followed by concurrent weekly carboplatin/paclitaxel with radiation doses escalated from 60 to 74 Gy. The median survival of 24 months, 3-year survival rate of 38%, and the high dose of radiation used justified a critical analysis of the technical and clinical components of this trial. METHODS AND MATERIALS: Between 1996 and 1999, 62 sequential patients with inoperable Stage IIIA/IIIB NSCLC were enrolled and treated with two cycles of induction carboplatin (area under the concentration curve = 6 using the Calvert equation) and paclitaxel (225 mg/m(2)), followed by an escalating radiation dose of 60-74 Gy with concurrent carboplatin weekly (area under the concentration curve = 2) and paclitaxel weekly (45 mg/m(2)). The goals of the trial were to determine whether 74 Gy of radiation could be safely delivered under these circumstances and whether patients could potentially benefit in terms of survival. The radiation treatment plans for all 62 patients were reviewed to determine the prechemotherapy and postchemotherapy tumor volume, as well as the dose-volume histograms of the normal lung and esophagus. RESULTS: Of the 62 patients who entered the trial, 48 completed the entire course of treatment. At last follow-up, 20 patients were alive (crude survival rate 32%). With a median follow-up of 43 months, the median survival was 24 months. The survival rate was 50% at 2 years and 38% at 3 years. Cox regression analysis showed that survival was best predicted by whether the patient had received radiotherapy (finished the trial), performance status, disease stage, and log postchemotherapy tumor volume. The 3-year survival rate for the 48 patients finishing the trial was 45%. Eight patients (13%) suffered locoregional relapse as the only site of failure. Only 1 patient had Grade 2 radiation pneumonitis. Five patients (8%) had Radiation Therapy Oncology Group Grade 3 or 4 esophagitis; 40 (65%) had a Grade 1 or 2 esophagitis. Esophageal toxicity could be predicted by the length of esophagus receiving 40 or 60 Gy. CONCLUSION: Radiation doses of 74 Gy, when given under the guidelines of the Lineberger Comprehensive Cancer Center 9603, appear to be safe and may possibly contribute to increased survival in patients with inoperable Stage IIIA/IIIB NSCLC.     

Squamous Cell Carcinoma of the Maxillary Sinus and the Oral Part of the Upper Jaw: Comparison of treatment results

The treatment results were compared in 77 patients with maxillary sinus squamous cell carcinoma (MC) and 53 patients with squamous cell carcinoma arising from the oral part of the upper jaw (OC). Both sets of patients received radiotherapy alone, or radiotherapy combined with surgery and/or chemotherapy. Computerized tomography was useful for the definition of the treatment volume. Inrraarterial chemotherapy was given in 89 of 130 patients and in these patients the total radiation dose was reduced by about 10 Gy. No difference was found in the 5-year survival rate between the MC (65%) and the OC (66%) groups. The cumulative incidence of local failure was higher in MC (36%) than in OC (26%), whereas the ultimate incidence of neck node metastasis was higher in OC (43%) than in MC patients (18%). Half of the inoperable patients (9/18) were older than 80 years and had contraindications to anaesthesia and major surgery. The local recurrence rate was high in the inoperable MC patients (6/8). Contralateral simus cancers occurred in 4 patients in the MC group.     

原发于上颌窦非霍奇金淋巴瘤15例临床分析

目的对原发于上颌窦非霍奇金淋巴瘤的临床、病理、治疗及预后结合文献进行分析。方法经手术后病理确诊为原发于上颌窦非霍奇金淋巴瘤15例在本院行放疗和化疗的综合治疗。放疗采用60Co-γ线或6MV~8MV高能X线,原发灶放疗中位剂量为56Gy,颈部放疗剂量为50Gy,颈部预防放疗剂量为44Gy。放射治疗前后行CHOP、COPP、COMP、BACOP等方案化疗2个~6个周期。结果5年生存率为53.4%。死亡8例,均死于远处转移。结论上颌窦非霍奇金淋巴瘤需行放射治疗和全身化疗,有条件时给予鞘内预防化疗。     

Clinical report of the treatment of locally advanced lung cancer.

This paper discusses the results of the treatment of 345 patients entered in the Veterans Administration Lung Group Protocol 13L. The study was activated March 1972, and closed for the patient accesion March 1975. All patients had a histological diagnosis of primary lung cancer considered clinically non-resectable or inoperable. Patients were equally randomized into two groups, radiotherapy alone or radiotherapy with chemotherapy. The analysis of the data included: treatment regimen, radiation dose, initial performance status, performance status change, cell type, duration of survival, quality of survival and age. The strongest influence on median survival was the level of radiation dose. The small cell carcinoma patients treated with radiotherapy and chemotherapy showed significant improvement in the median survival (38.2 weeks) over the patients treated with radiotherapy alone (20.6 weeks). The patients treated with radiotherapy and chemotherapy also showed improvement in performance status more frequently than the patients treated with radiotherapy alone. Other parameters of the analysis will be presented.     

Combination of external beam irradiation and high-dose-rate intraluminal brachytherapy for inoperable carcinoma of the extrahepatic bile ducts

PURPOSE: To assess the feasibility and therapeutic benefits of a combination of external beam radiotherapy (EBRT) and high-dose-rate intraluminal brachytherapy (ILBT) for treating patients with inoperable carcinoma of the extrahepatic bile ducts. METHODS AND MATERIALS: Of 31 patients who received RT at the Yonsei Cancer Center, Yonsei University College of Medicine in Seoul, Korea between 1986 and 1995, 17 patients underwent EBRT alone (Group 1) and 14 patients were treated with EBRT in combination with high-dose-rate ILBT (Group 2). After external drainage, EBRT was delivered with a total dose ranging from 36 to 55 Gy (median 50.4) in both groups. High-dose-rate ILBT for the patients in Group 2 was performed using a high-intensity (192)Ir source (Gamma-med remote afterloading system) within the expandable intrabiliary prosthesis (Gianturco stent), inserted transhepatically at the site of the obstruction. The radiation dose of the high-dose-rate ILBT was prescribed at 1.5 cm from the center of the source with a single daily dose of 5 Gy to a total of 15 Gy given in three fractions. The response rate, patterns of treatment failure, treatment morbidity, and survival data in the two groups were compared. RESULTS: Although locoregional recurrence was the most common pattern of failure in both groups, no statistically significant difference was found in the recurrence rates between those who did and did not receive ILBT (53% for Group 1 vs. 36% for Group 2; p > 0.05). However, a prolongation of the median time to tumor recurrence was observed in the Group 2 patients (5 months for Group 1 vs. 9 months for Group 2; p = 0.06). When the EBRT dose delivered was >50 Gy, most patients experienced various degrees of GI symptoms, but the frequency of radiation-induced complications in the two groups was similar. No enhancement in treatment morbidity was attributed to the addition of high-dose-rate ILBT to EBRT. With a median follow-up of 12 months, the overall actuarial 2-year survival rate for Group 2 patients was significantly better than that for Group 1 patients (0% for Group 1 vs. 21% for Group 2; p = 0.015). CONCLUSION: Given these observations, we believe that the combined use of EBRT and high-dose-rate ILBT is a beneficial, relatively safe, and effective method of improving the treatment outcome in selected patients with inoperable carcinoma of the extrahepatic bile ducts.     

Preoperative hyperthermia combined with radiotherapy and chemotherapy for patients with incompletely resected carcinoma of the esophagus

Two hundred eighty-nine patients with squamous cell carcinoma of the esophagus underwent subtotal esophagectomy from December 1965 to June 1986. Resection of esophageal carcinoma was absolutely noncurative in 64 patients (20%) due to invasion to the surrounding structures. These 64 patients were subdivided as follows into three groups based on the type of preoperative treatment: Group I included 16 patients without preoperative treatment; Group II included 38 patients with preoperative radiotherapy combined with chemotherapy (average doses: radiation 37.3 Gy, 1-(2-tetrahydrofuryl)-5-fluorouracil [tegafur] 8.4 g); Group III included 10 patients who underwent preoperative hyperthermia (42 degrees C to 45 degrees C) combined with chemotherapy and radiotherapy (average doses: radiation 33 Gy, bleomycin 33.9 mg, or cis-diamine dichloroplatinum 75 mg, hyperthermia 6.2 times). There were no significant differences in terms of postoperative therapy among the three groups. The median survival times for patients in Groups I, II, and III were 6, 7.5 and 11 months, respectively. The 2-year survival rates for patients in Groups I, II, and III were 0, 15.6%, and 34.3%, respectively. The prognosis in Group III was superior to that for Group I (P less than 0.05) and Group II. These results suggest that preoperative hyperthermia combined with radiotherapy and chemotherapy could prolong survival even in patients who have had noncurative resection.     

Ⅲ期非小细胞肺癌同步放化疗与单纯放疗的临床研究

目的：观察同步放化疗与单纯放疗治疗不能手术的ⅢＡ、ⅢＢ期非小细胞肺癌（ＮＳＣLＣ）的生存情况。方法：６２例ⅢＡ、ⅢＢ期ＮＳＣＬＣ患者被随机分成同步放化疗组（ｎ＝３２）和单纯放疗组（^ｎ＝３０）。单纯放疗组为原发灶和区域淋巴结前程超分割照射,每次１.２Ｇｙ,每天２次,总量４５.６Ｇｙ;后程加速超分割照射,每次1.６Ｇｙ,每天２次,肿瘤灶总量为６８Ｇｙ。同步放化疗组在放疗同时给予足叶乙甙５０ｍｇ／ｍ^２,顺铂２０ｍｇ／ｍ^２,第１～３、１５～１７、２９～３１天。结果：同步放化疗组中位无疾病进展生存期（ＰＦＳ）为１２个月,显著高于单纯放疗组８个月（Ｐ＝０.００２）。同步放化疗组中位总生存期（ＯＳ）为１６个月,显著高于单纯放疗组１４个月（Ｐ＝０.０１１）。同步放化疗组的１年生存率为８１.３％（２６／３２）,单纯放疗组的１年生存率为６３.３％（１９／３０）,两组无统计学差异（Ｐ＝０.１１４）。同步放化疗组的３年生存率为２5.５％,显著高于单纯放疗组３.３％（Ｐ＝０.０１６）。同步放化疗组的５年生存率为１５.６％,显著高于单纯放疗组０（Ｐ＝０.０２４）。结论：化、放疗同步治疗与单纯放射治疗相比能显著提高不能手术治疗的ⅢＡ、ⅢＢ期ＮＳＣＬＣ患者的长期生存率。     

Induction chemotherapy followed by concomitant chemoradiotherapy for non-small cell lung cancer

Multiple concepts of combined modality therapy for locoregionally advanced inoperable non-small cell lung cancer have been investigated. These include induction chemotherapy, concomitant chemoradiotherapy, and intensified radiation therapy schedules. To date, induction chemotherapy has been validated in randomized prospective trials versus radiotherapy alone. Concomitant chemoradiotherapy has led to promising results when combination chemotherapy regimens were used in the phase II setting. In addition, concomitant chemoradiotherapy has been shown to be superior to induction chemotherapy in direct comparison. Finally, accelerated radiotherapy has been shown to lead to improved locoregional control and survival in one randomized study. Based on these observations, the Cancer and Leukemia Group B (CALGB study 9431) investigated the addition of either vinorelbine, paclitaxel, or gemcitabine to cisplatin. In this trial, patients with locally advanced and inoperable non-small cell lung cancer received two cycles of induction chemotherapy with an additional two cycles of concomitant chemoradiotherapy utilizing the same agents accompanied by standard radiation to a total dose of 66 Gy. One hundred eighty-seven patients were entered on this study. An early analysis showed the median survival time was 17 months for all patients entered on the trial. In the context of other CALGB studies, the data from this trial are encouraging, and the regimens used warrant further study.     

Nasopharyngeal carcinomas: analysis of patient, tumor and treatment characteristics determining outcome.

PURPOSE: The present study reviews the experience in treatment of 447 patients with nasopharyngeal carcinomas, analyzing patient, tumor and treatment characteristics determining outcome. MATERIALS AND METHODS: There were 322 males and 125 females, their ages ranging from 7 to 85 years (median, 45 years). Two-hundred and seventy-two patients had World Health Organization (WHO) type 3 carcinomas, 123 patients had T4 tumors and 320 patients had metastatic cervical lymph nodes. Three-hundred and eight patients were treated with radiation therapy alone and 139 patients with chemotherapy in combination with radiation therapy. Cumulative radiation dose to primary tumor ranged from 50 to 76Gy (median, 70Gy) and radiation dose to metastatic cervical lymph nodes ranged from 46 to 74Gy (median, 66Gy). RESULTS: Follow-up ranged from 0.1 to 19.5 years (mean, 7.6 years). Local complete response was achieved in 357 patients. In multivariate analysis, T-classification, cumulative radiation dose to primary tumor and treatment with chemotherapy in combination with radiation therapy predicted local response. Nodal complete response was achieved in 272 patients. In multivariate analysis, N-classification and radiation dose to metastatic cervical lymph nodes predicted nodal response. Local failure was observed in 70 patients, nodal failure in 35 patients and systemic failure in 114 patients. Overall survival, disease-free survival and disease-specific survival were 33, 32 and 37%, respectively, at 10 years. In multivariate analysis, age, T-classification, N-classification, radiation dose and treatment with chemotherapy in combination with radiation therapy predicted overall survival whereas T-classification, N-classification, radiation dose and treatment with chemotherapy in combination with radiation therapy predicted both disease-free survival and disease-specific survival. CONCLUSIONS: Radiation therapy alone appears to be an adequate and viable treatment for patients with early-stage nasopharyngeal carcinomas, whereas treatment with chemotherapy in combination with radiation therapy appears to improve outcome for patients with advanced-stage nasopharyngeal carcinomas.     

External beam radiation therapy followed by high-dose-rate brachytherapy for inoperable superficial esophageal carcinoma

PURPOSE: The aim of this study was to retrospectively evaluate the feasibility, efficacy, and tolerance of external beam radiotherapy followed by high-dose-rate brachytherapy in inoperable patients with superficial esophageal cancer. PATIENTS AND METHODS: From November 1992 to May 1999, 66 patients with superficial esophageal cancer were treated with exclusive radiotherapy. The median age was 60 years (range, 41-85). Fifty-three percent of them were ineligible for surgery owing to synchronous or previously treated head-and-neck cancer. Most of the patients (n = 49) were evaluated with endoscopic ultrasonography (EUS) or computed tomography (CT). The mean doses of external beam radiotherapy and high-dose rate brachytherapy were 57.1 Gy (+/-4.83) and 8.82 Gy (+/-3.98), respectively. The most frequently used regimen was 60 Gy followed by 7 Gy at 5 mm depth in two applications. RESULTS: Among patients evaluated with EUS or CT, the complete response rate was 98%. The 3-, 5-, and 7-year survival rates were 57.9%, 35.6%, and 26.6%, respectively. Median overall survival was 3.8 years. The 5-year relapse-free survival and cause-specific survival were 54.6% and 76.9%. The 5-year overall, relapse-free, and cause-specific survival of the whole population of 66 patients was 33%, 53%, and 77%, respectively. Local failure occurred in 15 of 66 patients; 6 were treated with brachytherapy. Severe late toxicity (mostly esophageal stenosis) rated according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scale occurred in 6 of 66 patients (9%). CONCLUSION: This well tolerated regimen may be a therapeutic alternative for inoperable patients with superficial esophageal cancer. Only a randomized study could be able to check the potential benefit of brachytherapy after external beam radiation in superficial esophageal cancer.     

Management of nonsinonasal neuroendocrine carcinomas of the head and neck

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

膀胱癌放疗疗效分析

目的 回顾分析局限于盆腔的肌壁浸润性膀胱癌放疗疗效及影响因素、膀胱功能保存情况及不良反应。 方法 自1999-2016年在我院接受放疗的肌壁浸润性膀胱癌患者 45例(移行细胞癌 41例)。全膀胱 ±盆腔淋巴引流区 ±局部补量放疗,膀胱中位剂量45 Gy,肿瘤局部中位剂量56 Gy,24例接受了同步化疗,14例接受了新辅助化疗,29例放疗前接受过经尿道膀胱肿瘤电切术。 结果 中位随访28个月(4~101月),3年总生存率为51%,同步化放疗、单纯放疗 3年总生存率分别为64%、30%(P=0.001),有无新辅助化疗的 3年总生存率分别为59%和47%(P=0.540),放疗前有无局部电切的 3年总生存率分别为58%和43%(P=0.160),有无复发的 3年生存率分别为20%和79%(P=0.001)。局部复发 9例,远处转移 14例,放疗后≥3个月肠道损伤发生率2级 2例,泌尿道损伤发生率2级 4例、3级 2例。除 7例因膀胱肿瘤未控或放疗损伤严重影响患者膀胱功能外,其余均保持了基本正常膀胱功能。 结论 盆腔局限性肌壁浸润性膀胱癌同步化放疗可取得优于单纯放疗疗效,膀胱癌放疗后大部分患者可以保存正常膀胱功能,不良反应可接受。     

Combined chemotherapy and radiation versus radiation alone in the management of localized angiocentric lymphoma of the head and neck.

BACKGROUND AND PURPOSE: To clarify the clinical benefit derived from the combined modality therapy (CMT) comprised of chemotherapy and involved-field radiotherapy (XRT) for stage I and II angiocentric lymphomas of the head and neck. MATERIAL AND METHODS: Of 143 patients with angiocentric lymphoma of the head and neck treated at the Yonsei Cancer Center between 1976 and 1995, 104 patients (XRT group) received involved-field XRT alone with a median dose of 50.4 Gy (range: 20-70 Gy), while 39 patients (CMT group) received a median three cycles (range: 1-6 cycles) of chemotherapy before starting involved-field XRT. The response rate, patterns of failure, complications, and survival data of the XRT group were compared with those of the CMT group. RESULTS: Despite a higher response rate, local failure was the most common pattern of failure in patients of the both groups. The patterns of failure, including the systemic relapse rate were not influenced by the addition of combination chemotherapy. Although both modalities were well tolerated by the majority of patients, aberrant immunologic disorders or medical illnesses, such as a hemophagocytic syndrome, sepsis, intractable hemorrhage, or the evolution of second primary malignancies were more frequently observed in patients of the CMT group. The prognosis of patients in the XRT group was relatively poor, with a 5-year overall actuarial survival rate of 38% and disease-free survival rate of 32%, respectively. However, their clinical outcome was not altered by the addition of systemic chemotherapy. Achieving complete remission was the most important prognostic factor on univariate and multivariate analyses, but treatment modality was not found to be a prognostic variable influencing survival. CONCLUSIONS: Involved-field XRT alone for angiocentric lymphoma of the head and neck was insufficient to achieve an improved survival rate, but the combination of chemotherapy and involved-field XRT failed to demonstrate any therapeutic advantage over involved-field XRT alone.     

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.     

Locoregional treatment outcomes for inoperable anthracycline-resistant breast cancer

To assess the therapeutic outcomes and treatment-related morbidity of patients treated with radiation for inoperable breast cancer resistant to anthracycline-containing primary chemotherapy.

We analyzed the medical records of breast cancer patients treated on five consecutive institutional trials who had been designated as having inoperable locoregional disease after completion of primary chemotherapy, without evidence of distant metastases at diagnosis. The cohort for this analysis was 38 (4.4%) of 867 patients enrolled in these trials. Kaplan-Meier statistics were used for survival analysis, and prognostic factors were compared using log-rank tests. The median follow-up of surviving patients was 6.1 years.

Thirty-two (84%) of the 38 patients were able to undergo mastectomy after radiotherapy. For the whole group, the overall survival rate at 5 years was 46%, with a distant disease-free survival rate of 32%. The 5-year survival rate for patients who were inoperable because of primary disease extent was 64% compared with 30% for those who were inoperable because of nodal disease extent (p = 0.0266). The 5-year rate of locoregional control was 73% for the surgically treated patients and 64% for the overall group. Of the 32 who underwent mastectomy, the 5-year rate of significant postoperative complications was 53%, with 4 (13%) requiring subsequent hospitalization and additional surgical revision. Preoperative radiation doses of ≥54 Gy were significantly associated with the development of complications requiring surgical treatment (70% vs. 9% for doses <54 Gy, p = 0.0257).

Despite the poorer prognosis of patients with inoperable disease after primary chemotherapy, almost one-half remained alive at 5 years and one-third were free of distant disease after multidisciplinary locoregional management. These patients have high rates of locoregional recurrence after preoperative radiotherapy and mastectomy, and the morbidity associated with this approach may limit dose-escalation strategies. Alternative therapeutic strategies such as novel systemic agents, use of planned myocutaneous repair for closure, or radiation combined with radiosensitizing agents, should be considered in this class of patients.     

Phase II trial of paclitaxel, carboplatin, and concurrent radiation therapy for locally advanced non-small-cell lung cancer

We conducted a phase II trial to investigate the efficacy of concurrent chemoradiation in patients with stage III non-small-cell lung cancer (NSCLC). Thirty patients with inoperable NSCLC were enrolled onto a multicenter phase II trial of concurrent chemoradiation therapy. Patients received six weekly cycles of paclitaxel 45 mg/m(2) over 1 h; carboplatin at (area under the curve) AUC 2; and radiation therapy of 60 Gy. Radiation was administered to the primary tumor and regional lymph nodes (40 Gy over 4 weeks) followed by a boost to the primary tumor (20 Gy in 2 weeks). After the initial phase of concurrent chemoradiation, patients received an additional four cycles of paclitaxel 175 mg/m(2) over 3 h and carboplatin at AUC 6 every 3 weeks. The overall objective response rate of 30 assessable patients was 76.7%. At the median follow-up time of 13.1 months, the median survival time was 14.5 months (95% CI, 10.59-18.48). The median progression-free survival was 10.5 months (95% CI, 7.72-13.28). The major toxicity was hematologic. The incidence of grade 3 esophagitis was 10%. In conclusion, this chemoradiation regimen is well tolerated and shows significant clinical results for locally advanced NSCLC. Locoregional failure rate remains an important issue with this newer chemotherapeutic regimen. A novel chemotherapy and radiation therapy is clearly needed.     

诱导化疗加三维适形放疗同步化疗不可手术的局部晚期非小细胞肺癌的疗效分析

目的 探讨诱导化疗+三维适形放疗(3DCRT)联合顺铂单药(每周方案)同步化疗不可手术的局部晚期非小细胞肺癌(NSCLC)的疗效和毒副反应.方法 76例局部晚期NSCLC患者(ⅢA期42例,ⅢB期34例)先接受2个周期的诱导化疗,再行3DCRT(DT 64～74 Gy,中位68 Gy)+同步顺铂(25 mg/m2,每周1次,共6～7周)化疗.结果 诱导化疗后2例达CR,32例达PR,有效(CR+PR)率为45%.同步化放疗后8例达CR,47例达PR,有效率为72%.全组中位生存期和中位无进展生存期分别为16.6个月和10.3个月,1、2、3年总生存率和无进展生存率分别为67%、35%、21%和42%、15%、6%.ⅢA期和ⅢB期的中位生存期、中位无进展生存期分别为19.7个月和15.6个月、10.8个月和9.4个月.主要的毒副反应为放射性食管炎、放射性肺炎、恶心呕吐和白细胞减少.治疗后45例肿瘤局部复发或(和)远处转移,其中4例照射野内复发,3例癌性胸水,38例远处转移.结论 诱导化疗后3DCRT+顺铂单药同步化放疗不可手术的局部晚期NSCLC的疗效和耐受性较好,可进一步研究.     

A Randomized Feasibility Study Evaluating the Effect of Radiotherapy Alone Or Combined with 5-Fluorouracil in the Treatment of Locally Recurrent Or Inoperable Colorectal Carcinoma

The effect of radiotherapy alone or given simultaneously with 5-FU in the treatment of locally recurrent or inoperable colorectal carcinoma was investigated in a randomized feasibility trial. Twenty-nine patients were randomized to radiotherapy alone (50 Gy/5 weeks + 10-20 Gy boost), and 30 patients to the same radiotherapy with weekly 5-FU (600mg/m²) given before treatment every Monday during the first 5 weeks. The two groups were comparable with regard to age, sex, previous treatment, symptoms, tumour size and performance status. Treatment compliance to radiotherapy was the same in both groups with 87% receiving at least 50 Gy. Drug treatment was completed in 18/30 patients. Overall the treatment resulted in a significant palliative effect in 73% of evaluable patients with a median duration of 26 months, and objective response in 32% (8 CR, 11 PR), with a median duration of 18 months. The 3-year actuarial survival rate was 9% (median 12 months). Only patients who achieved CR became long-time survivors (63% 3-year actuarial survival). Similarly, performance status had a strong association with survival. Multivariate analysis showed complete response and high performance status to be the only parameters having prognostic influence on survival. Addition of 5-FU did neither influence the objective or symptomatic response, nor the development of distant metastases. However, addition of the drug resulted in an apparent increase in the frequency of severe acute radiation complications (33'/0 vs. 13% after irradiation alone).     

Late-course accelerated hyperfractionated radiotherapy for localized esophageal carcinoma

PURPOSE: To evaluate the long-term survival results and patterns of failure for localized carcinoma of the esophagus receiving late-course accelerated hyperfractionated (LCAF) radiotherapy (RT). METHODS AND MATERIALS: We studied 201 patients with histologically confirmed squamous cell carcinoma of the esophagus who were treated with LCAF RT between August 1994 and January 2000. The design of the radiation fields was based on the diagnosis by computed tomography and barium examination. All patients received conventionally fractionated RT at 1.8 Gy/d, five fractions weekly for the first two-thirds of treatment to a dose of about 41.4 Gy in 23 fractions within 4-5 weeks. This was followed by LCAF RT using reduced fields, 1.5 Gy/fraction twice daily with a 6-h interval between fractions, to a dose of about 27 Gy within 9 days. Thus, the total dose was 68.4 Gy in 41 fractions within 44 days. RESULTS: The incidence of Grade 3-5 acute radiation-induced bronchitis was 4.0% (8 cases), 3.0% (6 cases), and 0%, respectively. The incidence of Grade 3-5 acute radiation-induced esophagitis was 14.9% (30 cases), 0.5% (1 case), and 0%. Ten patients (5%) died of late complications. The 1-year, 3-year, and 5-year overall survival rate was 73%, 34%, and 26%, respectively. The 1-year, 3-year, and 5-year local control rate was 77%, 58%, and 56%, respectively. The main site of first failure was locoregional failure and distant metastasis (including lymph node metastasis from regional recurrence). Of 201 patients, 77 (38.4%) had local disease alone or with distant metastasis as the first failure, and 70 patients (34.9%) had distant metastasis and/or lymph node metastasis alone or with local failure as the first failure. CONCLUSION: The LCAF regimen offers similar local control and survival to standard chemotherapy plus RT, such as was delivered in the Radiation Therapy Oncology Group studies 85-01 and 94-05.     

A concurrent ultra‐fractionated radiation therapy and temozolomide treatment: A promising therapy for newly diagnosed,inoperable glioblastoma

We report on a phase II clinical trial to determine the effect of a concurrent ultra‐fractionated radiotherapy and temozolomide treatment in inoperable glioblastoma patients. A phase II study opened; patients over 18 years of age who were able to give informed consent and had histologically proven, newly diagnosed inoperable diagnosed and supratentorial glioblastoma were eligible. Three doses of 0.75 Gy spaced apart by at least 4 hr were delivered daily, 5 days a week for six consecutive weeks for a total of 67.5 Gy. Chemotherapy was administered during the same period, which consisted of temozolomide given at a dose of 75 mg/m² for 7 days a week. After a 4‐week break, chemotherapy was resumed for up to six cycles of adjuvant temozolomide treatment, given every 28 days, according to the standard 5‐day regimen. Tolerance and toxicity were the primary endpoints; survival and progression‐free survival were the secondary endpoints. In total, 40 patients were enrolled in this study, 29 men and 11 women. The median age was 58 years, and the median Karnofsky performance status was 80. The concomitant ultra‐fractionated radiotherapy and temozolomide treatment was well tolerated. Complete responses were seen in four patients, and partial responses were reported in seven patients. The median survival from the initial diagnosis was 16 months. Several long‐term survivors were noted. Concurrent ultra‐fractionated radiation therapy and temozolomide treatment are well accepted by the patients. The results showed encouraging survival rates for these unfavorable patients.