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

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

Uterine papillary serous carcinoma after radiation therapy for carcinoma of the cervix.

This article describes the clinicopathologic features of six cases of uterine papillary serous carcinoma (UPSC), which developed several years after radiation therapy (RT) for cervical carcinoma. The possible etiologic role of radiation is discussed, and the literature on endometrial carcinomas developing after RT is reviewed.     

A randomized trial comparing radiation therapy versus concomitant radiation therapy and chemotherapy in carcinoma of the thoracic esophagus.

From September 1982 to December 1985, 59 previously untreated patients with Stage II squamous cell carcinoma of the thoracic esophagus were randomly assigned to receive radiation therapy (RT) alone versus the concomitant use of RT and chemotherapy (CT) with 5-fluorouracil (5-FU), mitomycin C, and bleomycin (RT + CT). Thirty-one patients were randomized to the RT regimen and 28 to the RT + CT regimen. The complete local response rate was 58% for the RT group and 75% for the RT + CT group (P = 0.77). The median duration of response was 8 months for both groups. The overall 5-year survival rates were 6% and 16% (P = 0.16) for the RT and RT + CT groups, respectively. Acute toxicities were more pronounced in the RT + CT group. This clinical trial did not detect a difference in outcome with combined-technique therapy. This result must be interpreted with caution because of the small number of patients entered in this trial. Confirmation of the value or lack of value for combined therapy will require additional larger clinical trials.     

Indications of particle radiation therapy in the treatment of carcinoma of the esophagus.

Studies were made to evaluate the role of radiations in the treatment of carcinoma of the esophagus to confirm indications for charged particles. Results of the studies showed that prognosis of the patients treated with radiations depend strongly on length of tumor as well as on invasion of tumor cells into the adventitia of the esophagus. It was concluded that patients suffering from carcinoma of the esophagus less than 8 cm length are indicated for particle radiations.     

A controlled evaluation of combined radiation and bleomycin therapy for squamous cell carcinoma of the esophagus

In a controlled, randomized Eastern Cooperative Oncology Group (ECOG) study 77 evaluable patients with squamous cell carcinoma of the esophagus were treated with radiation therapy alone at a recommended dosage of 5000 to 6000 rad administered over five to six weeks in five or six fractions a week or with radiation given in combination with Bleomycin. Whereas the Bleomycin group experienced the additional toxicity of chemotherapy, Bleomycin did not contribute to therapeutic results in terms of either symptomatic palliation or survival. Further application of this approach by the methods we employed is not indicated. Overall treatment results were discouraging; the five year survival in this group of patients with regionally localized squamous cell carcinoma of the esophagus will not exceed 8%. In a non-randomized comparison, patients treated with 6000 rad did not show a therapeutic advantage over those treated with 5000 rad. Most favorable survival after treatment was seen in patients with lesions in the cervical esophagus and middle one-third of the thoracic esophagus. Least favorable survival was seen with lesions of the upper and lower one-third of the thoracic esophagus.     

60例高龄食管癌放射治疗分析

目的研究高龄食管癌患者放射治疗的特点。方法在积极对症,支持治疗的同时,对60例年龄在85-92岁之间的高龄食管癌患者以小照射野、低剂量进行常规放射治疗或适形精确放疗,放疗过程中经常进行食管造影、心肺功能检查。结果59例高龄食管癌患者安全地完成了放射治疗,未出现严重并发症,生存质量明显提高,生存时间明显延长,其中适形精确放疗效果更好,副作用更少。1例溃疡型食管癌患者疗程结束时出现食管穿孔,经食管支架植入后现已存活2年。结论高龄食管癌患者发现晚,病情严重,心、肺功能及全身状况差,放射治疗风险大,但在积极对症、支持治疗的同时,进行放射治疗是有意义的,不能追求大而全,包及所有肿瘤病灶的照射野,不能追求高剂量、高疗效,应经常进行检查,及时处理可能出现的并发症。     

Radiation therapy for squamous cell carcinoma of the esophagus

Between 1965 and 1981, 119 patients with squamous cell carcinoma of the esophagus were treated with radiation therapy with curative intent. Radiation was employed in combination with surgery and delivered pre- and/or postoperatively in 20 patients (17%). The remainder received radiotherapy alone. The overall survival rate was statistically higher in patients who had surgery and radiation compared to the group receiving radiation alone. The one-, two-, and five-year survival rates of patients receiving combined treatment vs radiotherapy alone were 65% vs 35%, 25% vs 14%, and 15% vs 6%. Age, total radiation dose, and inclusion of the supraclavicular areas in the radiation portals did not impact on outcome. Other prognostic factors are discussed. Long term survivors were noted to be at substantial risk for the development of a second epidermoid malignancy in the upper aerodigestive tract. Cumulative risk at five years was approximately 25%.     

Angiosarcoma after tylectomy and radiation therapy for carcinoma of the breast.

BACKGROUND. Angiosarcoma (AS) is an uncommon tumor that rarely develops after external beam radiation therapy (EBRT). Thirty-six cases have been reported in the literature. METHODS. The authors present two additional cases. Each of these patients received breast-conserving treatment for breast carcinoma that consisted of tylectomy and EBRT. In each case, AS developed in the field of prior irradiation. RESULTS. Currently, seven cases of AS after radiation therapy for breast-conserving treatment of breast carcinoma have been reported. The average time interval between the administration of radiation therapy and the development of AS is 8.6 years. CONCLUSIONS. This complication is rare and should not influence the decision to offer breast-conserving therapy to patients. However, patients should be informed that AS may develop as a result of radiation therapy.     

Postoperative radiation therapy after radical prostatectomy for prostate carcinoma.

BACKGROUND. The role and benefit of adjuvant radiation therapy after radical prostatectomy is unclear. This role was evaluated in 58 patients who, after undergoing radical prostatectomy for prostate carcinoma, had local extension of disease beyond the prostate or positive surgical margins. Thirty-nine patients treated surgically alone were compared with 19 patients who received adjuvant postoperative radiation therapy. All patients were followed for at least 5 years, and 50 patients had 10-year follow-ups. RESULTS. At 10 years, the actuarial local failure rate was 31% for patients treated with prostatectomy alone versus 6% for the group receiving postoperative radiation therapy (P less than 0.05). The actuarial survival and metastasis-free survival were similar for both groups. When patients with involved lymph nodes were excluded from analysis, the addition of radiation therapy resulted in improved recurrence-free survival (91% versus 46% at 10 years, P = 0.04) and in a trend toward improved metastasis-free survival (91% versus 55%, P = 0.08). Complications occurred in similar frequencies in both groups. CONCLUSIONS. In patients with local disease extension or positive surgical margins after radical prostatectomy, adjuvant radiation therapy improved local control and was administered with acceptable side effects.     

三维适形在中段食管癌放疗中的应用

目的:通过两种三维适形方案与常规方案的对比,明确三维适形技术在中段食管癌放疗中对脊髓及肺保护的优势。方法:对40例中段食管癌患者进行三种放疗方案的比较,A:常规方案(一前野两后斜野),B:在A方案的基础上加三维适形C:在B方案的基础上调整机架角度,实施一后斜野两前斜野。经CT模拟定位后每个病例均用三种方案在3D-TPS计划系统上模拟计算,以60Gy为处方剂量,100%剂量线包绕食管肿瘤,剂量分布评价指标为:18cm长度脊髓平均剂量,左肺平均剂量,左肺V20。结果:一后斜两前斜野的三维适形方案具有明显的优势,脊髓平均受量为11.89Gy,远低于常规方案的22.01Gy(P<0.01);左肺平均受量为16.09Gy,亦低于常规方案的18.01Gy,左肺V20平均值为28.67%,低于常规方案的33.87%。结论:中段食管癌的三维适形方案优于传统的常规方案。     

食管癌三维适形放射治疗剂量学与放射性肺炎发生相互关系的研究

目的:通过食管癌常规放射治疗与三维适形放射治疗的技术对比研究,比较应用不同外照射技术时肿瘤靶区适形指数的差异,以及肺等正常组织受照射容积剂量与放射性肺炎并发症发生概率(NTCP)的关系.方法:应用三维治疗计划系统,对28例胸中段EPC分别设计三种照射技术(A:常规3野;B:适形3野;C:适形5野).比较在同一处方剂量(66 Gy)时肿瘤靶区的适形指数,全肺受照射剂量与肺的NTCP的差异.结果:A、B、C三种照射技术比较:1)靶区的适形指数从0.55±0.09提高至0.76±0.04 和 0.78±0.06.2)肺平均剂量从(16.54±2.35) Gy降低至(13.26±1.93) Gy和(3.38±1.61) Gy;肺的V20从(32.95±6.43)%降低至(23.01±6.25)%和(24.8±4.47)%;肺的V30从(17.25±4.96)% 降低至(12.18±3.66)%和(6.75±2.93)%.3)肺的 NTCP从(6.9±6.86)%降低至(1.14±1.11)%和(1±1.02)%.A、B和C三种照射技术比较差异均有统计学意义,P=0.000.结论:三维适形放射治疗技术的靶区剂量分布较理想,显著降低正常肺的照射体积和剂量,减少放射性肺炎NTCP.     

Symptomatic local recurrence of prostate carcinoma after radiation therapy

BACKGROUND: Symptomatic local recurrence of prostate carcinoma (SLRPC) after radiation therapy (RT) is associated with morbidity and debilitating symptoms that have a substantial impact on the patient's quality of life. Most reports on the results of RT for localized prostate carcinoma (PC) do not address this endpoint. The objective of this study was to determine the incidence of SLRPC and to identify the risk factors for this endpoint. METHODS: The medical charts of 1006 patients who received RT for localized PC at the University of Texas M. D. Anderson Cancer Center between 1987 and 1997 were reviewed. Local symptoms were defined as hematuria, voiding symptoms, urinary obstruction, and pelvic pain. Progressive symptoms accompanied by either confirmatory histology or cystoscopic findings were attributed to PC. Univariate and multivariate analyses using Cox proportional hazards models were applied to identify risk predictors. RESULTS: Among 964 patients for whom follow-up data were available, 277 patients had prostate-specific antigen (PSA) progression, and 45 patients died of PC during a median follow-up of 9.4 years. In total, 33 patients (3.4%) developed SLRPC. In patients who experienced biochemical progression, the actuarial 5-year incidence of SLRPC was 8.3%. Among the patients who had developed SLRPC, 23 patients (69.7%) died of PC at a median of 25.3 months from the onset of local symptoms. Adverse histologic tumor subtypes (ductal, small cell, and sarcomatoid) were associated significantly with SLRPC (hazard ratio, 8.4; 95% confidence interval, 2.99-23.63). Clinical T classification at diagnosis, Gleason score, and initial PSA level showed a trend toward an increased hazard ratio. CONCLUSIONS: SLRPC after radiotherapy therapy was an uncommon but clinically significant event. Aggressive histologic subtypes were predictive of this endpoint. Clinical T classification, Gleason score, and initial prostate-specific antigen levels also may have predictive value.     

Extended-field radiation therapy for carcinoma of the cervix

The survival of cervical carcinoma patients with paraaortic/high common iliac nodal metastases was evaluated by retrospective chart review during a 13-year interval. Thirty-three patients with cervical carcinoma and surgically documented nodal metastases received primary, extended-field radiation therapy. Overall 2-year and 5-year actuarial survival rates after diagnosis were 37% and 31%, respectively. Survival was analyzed in terms of the variables patient age, clinical stage, tumor histologic type, the presence of enlarged paraaortic/high common iliac lymph nodes, the extent of nodal involvement (microscopic versus macroscopic), the presence of intraperitoneal disease, and whether intracavitary brachytherapy was administered. The use of intracavitary radiation therapy was associated with improved local control and survival (P = 0.017). None of the other variables were statistically related to patient survival. Twenty-two of the patients died of cervical cancer and five are surviving without evidence of cancer. Four patients died of intercurrent disease. Two patients developed bowel-related radiation complications; both patients received chemotherapy concurrent with the radiation therapy. One of the two patients died of radiation enteritis. The use of extended-field radiation therapy does benefit a small group of patients and may result in extended patient survival.     

Twice-a-day radiation therapy for supraglottic carcinoma

This is a report of a group of 106 patients with supraglottic carcinomas treated by the twice-a-day radiation therapy program at the Massachusetts General Hospital from October 1979 through April 1984. The program consisted of 1.6 Gy per fraction, 2 fractions a day, 5 days a week for a total of 64 Gy with 2 weeks rest after the twelfth b.i.d. day. The local control of this group of patients was compared to that of 79 patients treated by the conventional once-a-day program with a daily fraction of 1.8 Gy for a total of 65 Gy, at the same institution during the 4 years immediately prior to the b.i.d. program. The 3 year actuarial local control rate for the entire group following the twice-a-day program was 76% as compared to 50% after the once-a-day program. The difference was significant, p = 0.001. For the T1 and T2 lesions, the corresponding rates were 88 and 63%, respectively, with a p value of 0.029. The rates for T3 and T4 lesions were 66 and 33%, respectively, p = 0.0037. The study indicated that the twice-a-day radiation therapy program as outlined is effective in treatment of supraglottic carcinoma, and is more markedly effective in advanced lesions. Late radiation effects are minimal and salvage surgery is possible for radiation therapy failures. To date, no patient developed radiation myelitis following the b.i.d. program with the dose to the spinal cord limited to 38.4 Gy in 2.5 weeks.     

Three-dimensional conformal radiation therapy for squamous cell carcinoma of the esophagus: A prospective phase I/II study

Purpose

A prospective phase I-II study was conducted to determine the tolerance and local control rate of three-dimensional conformal radiotherapy (3-DCRT) for esophageal squamous cell carcinoma (SCC).

Methods and materials

Thirty patients underwent 3-DCRT for thoracic esophageal SCC. PTV1 composed of a 1.2-1.5 cm margin lateral around GTV and 3.0 cm margin superior/inferior of GTV. PTV2 encompassed GTV with a margin of 0.5-0.7 cm. The dose for PTV1 was 50 Gy in 2 Gy daily fractions; PTV2 received a boost of 16 Gy in 2 Gy daily fractions to a total dose of 66 Gy.

Results

Median follow-up time was 18 months. The most common acute toxicity was esophagitis in 63% of patients with RTOG grades 1-2, and in 3% with grade 3. RTOG grades 1-2 radiation pneumonitis developed in 27% of patients. One patient developed pulmonary fibrosis RTOG grade 2 and another patient experienced grade 3 pulmonary fibrosis. Two patients developed mild esophageal stricture requiring dilatation. Two-year overall survival, local disease progression-free rate, and distant metastasis-free rate were 69%, 36% and 56%, respectively.

Conclusions

Although 3-DCRT to 66 Gy for esophageal SCC was well tolerated, the local control was disappointing. The result supports the use of chemoradiation as the standard care for esophageal SCC.