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.     

化疗与后程加速超分割联合治疗食管癌临床观察

目的评价化疗联合后程加速超分割放射治疗食管癌的疗效.方法70例食管癌患者,随机分为2组,化放组36例,单纯放疗组34例.放疗采用60Co γ线外照射,先前一后二野等中心照射40 Gy后改用后程加速超分割放疗,(2次/d,1.5 Gy/次),全疗程总剂量共67～70Gy,化疗采用5-FU CF DDP.结果化放组与单放组1、3、5年生存率分别为71.0%、51.6%、29.1%和48.1%、30.0%、10.2%,两组对比差异有显著性(P＜0.05)结论化疗加后程加速超分割治疗食管癌能提高生存率,患者容易耐受.     

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.     

Duodenal adenocarcinoma: patterns of failure after resection and the role of chemoradiotherapy

PURPOSE: To report patterns of disease recurrence after resection of adenocarcinoma of the duodenum and compare outcomes between patients undergoing surgery only vs. surgery with concurrent chemotherapy and radiation therapy (CT-RT). METHODS AND MATERIALS: This was a retrospective analysis of all patients undergoing potentially curative therapy for adenocarcinoma of the duodenum at Duke University Medical Center and affiliated hospitals between 1975 and 2005. Overall survival (OS), disease-free survival (DFS), and local control (LC) were estimated using the Kaplan-Meier method. Univariate regression analysis evaluated the effect of CT-RT on clinical endpoints. RESULTS: Thirty-two patients were identified (23 M, 9 F). Median age was 60 years (range, 32-77 years). Surgery alone was performed in 16 patients. An additional 16 patients received either preoperative (n = 11) or postoperative (n = 5) CT-RT. Median RT dose was 50.4 Gy (range, 12.6-54 Gy). All patients treated with RT also received concurrent 5-fluorouracil-based CT. Two patients treated preoperatively had a pathologic complete response (18%), and none had involved lymph nodes at resection. Five-year OS, DFS, and LC for the entire group were 48%, 47%, and 55%, respectively. Five-year survival did not differ between patients receiving CT-RT vs. surgery alone (57% vs. 44%, p = 0.42). However, in patients undergoing R0 resection, CT-RT appeared to improve OS (5-year 83% vs. 53%, p = 0.07). CONCLUSIONS: Local failure after surgery alone is high. Given the patterns of relapse with surgery alone and favorable outcomes in patients undergoing complete resection with CT-RT, the use of CT-RT in selected patients should be considered.     

后程适形放射治疗联合ＮＰ方案同步化疗治疗Ⅲ期非小细胞肺癌

目的　观察三维适形放射治疗联合长春瑞滨（ＮＶＢ）加顺铂（ＤＤＰ）同步化疗治疗Ⅲ期非小细胞肺癌（ＮＳＣＬＣ）的疗效及耐受性。方法　５０例Ⅲ期ＮＳＣＬＣ患者随机分为同步放化疗组和单放组,每组各２５例。单放组采用６ＭＶ或１５ＭＶＸ线常规外放疗ＤＴ４０Ｇｙ,后采用三维适形放疗２.５～３Ｇｙ／ｆ,１ｆ／ｄ,至ＤＴ７０～７５Ｇｙ,同步放化疗组在放疗的第１～３天联合ＮＰ方案化疗（ＮＶＢ２５ｍｇ／ｍ^２,ｄ_１、ｄ_８,ＤＤＰ３０ｍｇ／ｍ^２,ｄ_１～ｄ_３）,２１天为１周期,放疗后再采用该方案化疗３～６个周期。结果　同步放化疗组与单放组的有效率（ＣＲ＋ＰＲ）分别为８４.０％和６４.０％（Ｐ＞０.０５）;１、２年生存率分别为７６.０％、３６.０％和６８.０％、２４.０％（Ｐ均＞０.０５）。主要毒副反应表现为骨髓抑制和消化道反应。结论　后程三维适形放射治疗联合ＮＰ方案同步化疗治疗Ⅲ期ＮＳＣＬＣ近期疗效好,且毒性反应可以耐受。     

Concurrent CMF and radiation therapy for early stage breast cancer: results of a pilot study

PURPOSE: The optimal sequencing of chemotherapy (CT) and radiotherapy (RT) for patients with early-stage breast cancer treated with breast-conserving therapy is unresolved. Given the concerns arising from delaying either CT or RT, we conducted a pilot study of a concurrent CT-RT regimen in the hope that this would reduce side effects without decreasing efficacy. METHODS AND MATERIALS: From 1992-1994, 112 patients with 0-3 positive nodes received 6 monthly cycles of classic oral chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil (5-FU) (CMF). On day 15 of cycle 1, patients started tangential field RT (39.6 Gy in 22 fractions), followed by a 16 Gy boost in 8 fractions. Median follow-up time for surviving patients was 53 months. RESULTS: Moist desquamation developed during or shortly after RT in 50% of patients, but only 5 patients required treatment breaks. Grade 4 neutropenia during RT occurred in 16 patients, but only 1 required hospitalization. One patient developed Grade 2 radiation pneumonitis. Ninety-three percent of patients received at least 85% of prescribed drug doses. Cosmetic scores of 51 evaluable patients approximately 2 years after the end of chemotherapy were 47% excellent, 43% good, and 10% fair. We have observed 4 local failures and 20 distant failures. CONCLUSIONS: This concurrent CT-RT scheme had acceptable toxicity and outcome. Further comparison of this approach allowing prompt initiation of both CT and RT to alternative sequences is warranted.     

Multi-institutional review of repeat irradiation of chest wall and breast for recurrent breast cancer

PURPOSE: To review the toxicity and clinical outcomes for patients who underwent repeat chest wall or breast irradiation (RT) after local recurrence. METHODS AND MATERIALS: Between 1993 and 2005, 81 patients underwent repeat RT of the breast or chest wall for locally recurrent breast cancer at eight institutions. The median dose of the first course of RT was 60 Gy and was 48 Gy for the second course. The median total radiation dose was 106 Gy (range, 74.4-137.5 Gy). At the second RT course, 20% received twice-daily RT, 54% were treated with concurrent hyperthermia, and 54% received concurrent chemotherapy. RESULTS: The median follow-up from the second RT course was 12 months (range, 1-144 months). Four patients developed late Grade 3 or 4 toxicity. However, 25 patients had follow-up >20 months, and no late Grade 3 or 4 toxicities were noted. No treatment-related deaths occurred. The development of Grade 3 or 4 late toxicity was not associated with any repeat RT variables. The overall complete response rate was 57%. No repeat RT parameters were associated with an improved complete response rate, although a trend was noted for an improved complete response with the addition of hyperthermia that was close to reaching statistical significance (67% vs. 39%, p = 0.08). The 1-year local disease-free survival rate for patients with gross disease was 53% compared with 100% for those without gross disease (p < 0.0001). CONCLUSIONS: The results of our study have shown that repeat RT of the chest wall for patients with locally recurrent breast cancer is feasible, because it is associated with acceptable acute and late morbidity and encouraging local response rates.     

Protracted venous infusion 5-fluorouracil with concomitant radiotherapy compared with bolus 5-fluorouracil for unresectable pancreatic cancer

Radiation therapy (RT) with concurrent 5-fluorouracil (5-FU) administered by protracted venous infusion (PVI) replaced our prior institutional protocol of RT with bolus administration of 5-FU as standard therapy for unresectable pancreatic cancer in 1994. In this article, we compare the treatment intensity, toxicity, and outcome for patients with unresectable pancreatic cancer treated on these sequential protocols. Fifty-four patients, 27 on each protocol, with biopsy-confirmed pancreatic cancer received chemoradiotherapy. The radiotherapy field included the gross tumor volume and regional lymph nodes to a dose of 45 Gy, followed by "boost" to the gross tumor volume to 54 Gy to 60 Gy. From 1987 to 1994, patients received concurrent 5-FU administered by bolus injection, at a dose of 500 mg/m2 on days 1 to 3 and days 29 to 31 of RT. After December 1994, 5-FU was administered by PVI (200-250 mg/m2) beginning on day 1 and continuing until the completion of RT. The chemotherapy treatment intensity was increased in the group receiving 5-FU by PVI, as evidenced by an increased average weekly and cumulative dose of 5-FU (p < 0.01). The radiotherapy treatment intensity was equivalent between the two groups. The incidence of objectively quantified toxicity was not statistically different between treatment groups. Overall survival remained poor in both treatment groups. With a median follow-up of 18 months (range: 3-30 months) for surviving patients, the 6-month, 1-year, and 2-year survivals for the PVI 5-FU-treated group versus the bolus 5-FU-treated group were 56% versus 52%, 34% versus 18%, and 22% versus 13%, respectively (p = 0.9). Radiotherapy with concomitant 5-FU by PVI results in a greater weekly and total dose of chemotherapy. The method of 5-FU administration (bolus versus PVI) did not change the RT treatment intensity, experienced toxicity, or overall survival.     

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.     

Concurrent weekly cisplatin and radiotherapy in routine management of cervical cancer: a report on patient compliance and acute toxicity

PURPOSE: To evaluate patient compliance and acute toxicity accompanying concurrent weekly cisplatin and radiotherapy (RT) in the routine management of cervical cancer. METHODS AND MATERIALS: Locally advanced or high-risk early-stage cervical cancer patients treated with RT and concurrent weekly cisplatin at a dose of 40 mg/m(2) i.v. (maximum dose, 70 mg) for five cycles. Definitive RT included whole pelvis external beam RT to the International Commission on Radiation Units and Measurements reference dose of 40 Gy plus a 10-Gy boost to the parametrium and two brachytherapy applications of 20 Gy to point A each. Postoperative RT consisted of pelvic external beam RT to the International Commission on Radiation Units and Measurements reference dose of 50 Gy and one brachytherapy application of 30 Gy at a depth of 0.5 cm from the applicator surface. RESULTS: Included in this analysis were 112 consecutive cervical cancer patients treated at one institution with concurrent cisplatin and RT between May 1999 and September 2002. The median age was 48 years (range, 28-79 years). Definitive RT was administered to 57 International Federation of Gynecology and Obstetrics "bulky" Stage IB or IIB-IVA patients, and 53 patients underwent postoperative RT; 2 patients underwent RT for stump carcinoma. All but 2 patients (both administered definitive RT) completed RT. A total of 454 cisplatin cycles were administered (median 4 cycles/patient, range 1-6). Overall, 74% of patients received at least four cycles of cisplatin. The planned five cisplatin cycles were administered to 50 patients (45%); 42% were irradiated definitively and 47% postoperatively. The full and timely planned cisplatin dose was administered to 29 patients (26%). For 29% of patients, the interval between cycles was prolonged because of toxicity (n = 11; 10%) or for reasons not related to toxicity (n = 10; 9%). Of the 112 patients, 62 (55%) did not undergo the planned five cycles of cisplatin because of treatment toxicity (n = 35; 31%) or noncompliance with the treatment schedule because of delayed administration of the first cycle or omission of a cycle for reasons other than toxicity (n = 23; 21%). The most common side effects resulting in chemotherapy discontinuation included GI complications (n = 7) and impaired renal function (n = 5). Of the 112 patients, 49 (44%) experienced Grade 1 or 2 leukopenia and 6 (5%) Grade 3 or 4 leukopenia. CONCLUSION: Our results show that pelvic RT combined with weekly cisplatin in cervical cancer patients is accompanied by considerable acute toxicity. Furthermore, a number of patients were unable to comply with the treatment schedule owing to reasons unrelated to treatment toxicity. Thus, administration of the full chemotherapy dose may be difficult, although the delivery of planned RT was generally not compromised. Additional follow-up is needed to assess the late toxicity of combined modality treatment.     

Chemotherapy with concurrent brain and thoracic radiotherapy in brain-only metastases of treatment naive small-cell lung cancer: a phase II study

To study the treatment outcomes of brain-only metastases from small-cell lung cancer (SCLC) at initial diagnose treated by chemotherapy with concurrent brain and thoracic radiotherapy (RT). From Jan 2004 to Jan 2009, 36 treatment-na?ve SCLC patients with brain-only metastases in Sun yat-sen University were enrolled. Treatment contained initial EP chemotherapy with concurrent whole-brain radiotherapy (WBRT). EP regimen consisted of etoposide 100 mg/m(2) IV d1-3, cisplatin 80 mg/m(2) IV d1, repeated every 3 weeks. WBRT with total dose of 30 Gy in 10 fractions was started within 1 week from the beginning of chemotherapy followed by thoracic RT including 2 Gy once daily to a total dose of 60 Gy. Treatment responses were evaluated after 3 cycles of chemotherapy. EP regimen was given totally 6 cycles for no tumor progression. Thirty-four patients were evaluable. All of the 20 CNS symptomatic patients experienced symptoms relief. Objective responses in the brain and primary thoracic lesions were observed in 26 (76.5%, 16CR + 10PR) and 29 (85.3%, 23CR + 6PR) patients, respectively. The median survival time (MST) was 19.2 months, and the 1-and 2-year overall survival rates (OS) were 70.6 and 29.4%, respectively, in all patients. Patients with CR response had the longest MST of 21.9 months and 1-and 2-year OS of 93.8 and 43.8%, respectively. Treatment toxicity profiles were acceptable. The treatment strategy of concurrent chemotherapy with brain and thoracic RT might achieve promising survival outcomes comparable to limited-stage SCLC in initially diagnosed SCLC with brain-only metastases.     

放疗联合周剂量紫杉醇治疗老年食管癌的临床研究

目的探讨放疗联合周剂量紫杉醇治疗老年食管癌的疗效及毒副反应。方法 49例老年食管癌患者随机分为同步放化疗组（24例）和单纯放疗组（25例）,2组放疗均采用常规分割,照射剂量60~66 Gy。同步放化疗组紫杉醇60 mg,每周1次,连续6周。结果同步放化疗组有效率87.5%,高于单纯放疗组的60.0%（P〈0.05）。同步放化疗组Ⅱ、Ⅲ度白细胞减少占54.2%,明显高于单纯放疗组的20.0%（P〈0.05）。结论放疗联合周剂量紫杉醇治疗老年食管癌近期疗效较好,毒副反应相对加重但可耐受。     

Concurrent radiation, mitomycin C and 5-fluorouracil in poor prognosis carcinoma of cervix: preliminary results of a phase I-II study

Between July 1981 and June 1983, 27 patients with advanced primary squamous cell carcinoma (SCC) of cervix (FIGO Stages IIIB, IVA or extensive nodal involvement) and 8 with recurrent disease were treated using a pilot regimen of combination chemotherapy (CT): Mitomycin C (MIT), 5 Fluorouracil (5 FU), and radiation therapy (RT). CT and RT doses on this Phase I-II Study were escalated to the current regimen. A split course of RT was used, either pelvic RT alone (4560 Gy in 28 fractions) or the same pelvic RT plus para-aortic RT (3600 Gy in 24 fractions). CT was given: MIT 6 mg/M2 IV push day 1, and 5 FU 1.0 g/M2 (maximum daily 1.5 g) by continuous IV infusion days 1 through 4 of each half-course of RT. This was followed by one application of intrauterine 137Cs when possible. Three of the 8 patients with recurrence in the pelvis or para-aortic nodes had a complete response (CR) to CT-RT and are alive without disease at 19, 19 and 22 months after treatment, respectively. Twenty of the 27 (74%) primary patients had a CR. With a median duration of follow-up of 6 months 4/20 have relapsed, 1 in RT field, 2 at distant sites, and 1 in both. Pelvic disease remains controlled in 19/27 (70%) including one patient salvaged with surgery. The acute toxicity of this regimen was tolerable: 2/35 developed transient leukopenia with one febrile episode, 9/35 developed transient thrombocytopenia without bleeding. Symptomatic sigmoid strictures developed in two patients, one requiring surgical intervention. Sigmoid perforation occurred in one patient and contributed to death. Typically, near complete regression of tumor is noted on completion of the external RT, reproducing the dramatic responses that have been observed in SCC of the anal canal, esophagus and head and neck, with this CT-RT regimen. A Phase III Study is required to establish whether the enhanced response rates to CT-RT will result in increased pelvic control and cure rates compared to those after RT alone.     

早期宫颈癌术后每周紫杉醇+顺铂同步3DCRT的Ⅰ期临床研究

目的 明确中国人每周紫杉醇和顺铂同步盆腔放疗早期宫颈癌术后患者的MTD。方法 顺序选择有高中危因素的早期宫颈癌术后患者25例,ECOG≤2。盆腔采用6、10 MV X线4个野3DCRT,照射剂量为40 Gy分20次后予盆腔中央挡铅,宫旁加量10~20 Gy分5~10次;¹⁹²Ir高剂量率腔内照射,参考点为阴道黏膜下0.5 cm,处方剂量为5 Gy/次共2~4次。化疗起始剂量为每周紫杉醇 10 mg/m²、顺铂 20 mg/m²,共6个周期。利用3+3设计方法,每3例患者进行剂量递增直至达到DLT水平。结果 入组患者均在7周内完成外照射和腔内照射。第7剂量组4例患者中2例4周期后出现DLT即3级腹泻。3、4级血液学反应主要为白细胞、中性粒细胞减少,主要发生在4~6周期化疗后。第6剂量组1例出现4级白细胞、中性粒细胞减少,但额外增加的3例未出现4级反应。同步化疗未延迟治疗时间。25例患者中22例完成了6周期化疗。中位随访时间59.5个月,3例患者死于复发转移,1例死于呼吸衰竭。结论 早期宫颈癌术后盆腔照射联合每周紫杉醇和顺铂的同步放化疗安全、耐受性好。中国人的MTD为6周期的每周顺铂35 mg/m²和紫杉醇30 mg/m²。     

Chemoradiotherapy for advanced head and neck cancer — Analysis of a prospective, randomized trial

Objective: To study the efficacy of neo-adjuvant chemotherapy followed by radiotherapy in advanced head and neck cancer.Study design: Randomised, prospective study.Setting: Tertiary academic referral center.Patients: One hundred and eighty patients of advanced head and neck squamous cell carcinoma.Intervention: Patients were randomized into two arms. The study arm (CT-RT arm) received 3 cycles of anterior chemotherapy with Inj. Cisplatin 100 mg/m² on D₁ and Inj 5F.U. 700 mg/m² on D₁-D₄ at an interval of 21 days, followed by external radiation. The control arm (RT arm) received external radiotherapy only. The dose of Radiotherapy was 64 to 68 Gy in conventional fractionation.Results: Patients of CT-RT showed better tumour control locally than patients who received only RT. Toxicities were commoner in CT-RT arm but they were manageable. 5 year survival is higher in the CT-RT arm (21% vs 16%; p value> 0.05).Conclusion: Anterior chemotherapy with Cisplatin and 5F.U. is associated with good clinical response which is translated into increased survival along with acceptable toxicities.     

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.     

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.     

Hyperfractionated radiotherapy with concurrent chemotherapy for advanced esophageal cancer

The clinical efficacy and safety of hyperfractionated radiotherapy with concurrent chemotherapy were studied retrospectively in patients with primary advanced esophageal cancer. The subjects were 31 patients who were treated with hyperfractionated radiotherapy and concurrent chemotherapy in our institution between 1990 and 2001. The chemoradiotherapy consisted of cisplatin 70-80 mg/m2 on day one, and continuous infusion of 5-fluorouracil 700-800 mg/m2/24 hours on days 1 to 3, with concurrent hyperfractionated radiotherapy (57.6-72 Gy). Complete remission (CR) was observed in 17 cases, and partial response in 13 cases (response rate: 96. 7%). Three-year survival rate and 5-year survival rate were 35.5% and 26.3%, respectively. Grade 3/4 hematological toxicities included leukocytes in 7 patients (22.6%), hemoglobin in 6 patients (19.4%), and platelets in 4 patients (12.9%). Grade 3 dysphagia-esophageal related to radiation was observed in 3 patients (9.7%). Late toxicities occurred with the following incidences: hypothyroidism in 2 patients, benign esophageal strictures in 2 patients, pericardial effusion in 8 patients, and pleural effusion in 8 patients. The results suggest that combined chemotherapy and hyperfractionated radiotherapy is an effective and well-tolerated regimen.     

紫杉醇与顺铂同步化疗联合放疗治疗老年食管癌33例分析

[目的]探讨紫杉醇与顺铂同步化疗联合放疗治疗老年食管癌患者的疗效和安全性。[方法]33例局部晚期老年食管鳞癌患者,采用根治性同步放化疗,放疗剂量60Cy（分两阶段进行）,放疗的第1d和第29d给予紫杉醇（135mg／m^2,d1）和顺铂（20mg／m^2,d1）化疗。[结果]81．81％的患者完成了治疗计划,24．24％的患者放疗总时间延长;Ⅲ级以上急性毒副反应主要为造血系统毒性（白细胞减少21.21％、血红蛋白减少3．03％、血小板减少12．12％）,放射性食管炎（18．18％）,肌肉酸痛（6．06％）,放射性皮炎（6．06％）,远期毒性反应主要为食管狭窄（15．15％）、放射性肺损伤（6．06％）;中位生存时间18．17个月,5年生存率、局控率、无瘤生存率分别为22．85％、30．90％和18．29％。[结论]紫杉醇与顺铂同步化疗联合放疔治疗老年性食管癌的毒副反应可耐受．值得临床推广应用。