Patterns of failure for stage I ampulla of Vater adenocarcinoma: a single institutional experience

Background

Ampullary adenocarcinoma is a rare malignancy associated with a relatively favorable prognosis. Given high survival rates in stage I patients reported in small series with surgery alone, adjuvant chemoradiotherapy (CRT) has traditionally been recommended only for patients with high risk disease. Recent population-based data have demonstrated inferior outcomes to previous series. We examined disease-related outcomes for stage I tumors treated with pancreaticoduodenectomy, with and without CRT.

Methods

All patients with stage I ampullary adenocarcinoma treated from 1976 to 2011 at Duke University were reviewed. Disease-related endpoints including local control (LC), metastasis-free survival (MFS), disease-free survival (DFS) and overall survival (OS) were analyzed using the Kaplan-Meier method.

Results

Forty-four patients were included in this study. Thirty-one patients underwent surgery alone, while 13 also received adjuvant CRT. Five-year LC, MFS, DFS and OS for patients treated with surgery only and surgery with CRT were 56% and 83% (P=0.13), 67% and 83% (P=0.31), 56% and 83% (P=0.13), and 53% and 68% (P=0.09), respectively.

Conclusions

The prognosis for patients diagnosed with stage I ampullary adenocarcinoma may not be as favorable as previously described. Our data suggests a possible benefit of adjuvant CRT delivery.     

Treatment of superficial esophageal cancer by external radiation therapy alone: results of a multi-institutional experience

PURPOSE: To assess the effectiveness and toxicity of external radiation therapy for superficial esophageal cancer. METHODS AND MATERIALS: During the period from March 1979 to November 1996, 78 patients with superficial esophageal cancer received radiation therapy without intracavitary irradiation at nine radiotherapy institutions in Japan. All patients had histologically-proven squamous cell carcinoma. Endoscopic ultrasonography was performed in 34 patients to discriminate mucosal from submucosal cancer. Most of the patients had received radiation therapy using conventional fractionation at an average dose of 65.5 Gy. RESULTS: The survival rates at 1, 2, and 5 years were 88%, 73%, and 45%, respectively. The local control rates at 1, 2, and 5 years were 85%, 79%, and 66%, respectively. Although the difference was not significant, the survival rate of cancer patients with a tumor invading the submucosa was lower than that of the other patients. In 6 mucosal cancer patients, local recurrence was observed in 1 patient with extensive cancer. Regional lymph node recurrence and distant failure were not observed in mucosal cancer patients, while in 28 submucosal cancer patients, the 5-year survival rate and relapse free rate were only 49% and 43%, respectively. Univariate and multivariate analysis identified age as the only significant prognostic factor. Severe late injury, such as esophageal ulcer, perforation, and bleeding, was not observed. CONCLUSION: External radiation therapy is effective for mucosal cancer. However, further investigation is needed to establish a better standard treatment protocol for submucosal cancer.     

Primary radiation therapy for stage I and II breast cancer

In 1987 there were estimated to be approximately 130,000 new cases of breast cancer diagnosed in the United States. Presently, about 20-30,000 of these cases are treated with primary radiotherapy, although many more of the 90,000 stage I and II breast cancer cases are eligible for this form of treatment. Appropriate selection must be employed, including the size and site of the primary tumor, the size of the breast, the potential for multifocal disease, and the age of the patient. When proper selection is used, primary radiotherapy for stage I and II disease yields equivalent overall survival and NED survival when compared to traditional mastectomy. The benefit is preservation of the breast with good to excellent cosmesis in the vast majority of patients.     

Postoperative extended-volume external-beam radiation therapy in high-risk esophageal cancer patients: a prospective experience

Background and Purpose

Extended-volume external-beam radiation therapy (rt) following esophagectomy is controversial. The present prospective study evaluates the feasibility of extended-volume rt treatment in high-risk esophagectomy patients with a cervical anastomosis receiving postoperative combined chemoradiation therapy.

Patients and Methods

From 2001 to 2006, 15 patients with resected esophageal cancer were prospectively accrued to this pilot study to evaluate the adverse effects of extended-volume rt. Postoperative management was carried out at London Regional Cancer Program. Eligibility criteria were pathology-proven esophageal malignancy (T3–4, N0–1), disease amenable to surgical resection, and esophagectomy with or without resection margin involvement. Patients with distant metastases (M1) and patients treated with previous rt were excluded. All 15 study patients received 4 cycles of 5-fluorouracil–based chemotherapy. External-beam rt was conducted using conformal computed tomography planning, with multi-field arrangement tailored to the pathology findings, with coverage of a clinical target volume encompassing the primary tumour bed and the anastomotic site in the neck. The radiation therapy dose was 50.40 Gy at 1.8 Gy per fraction. The rt was delivered concurrently with the third cycle of chemotherapy. The study outcomes—disease-free survival (dfs) and overall survival (os)—were calculated by the Kaplan–Meier method. Treatment-related toxicities were assessed using the U.S. National Cancer Institute’s Common Toxicity Criteria.

Results

The study accrued 10 men and 5 women of median age 64 years (range: 48–80 years) and TNM stages T3N0 (n = 1), T2N1 (n = 2), T3N1 (n = 11), and T4N1 (n = 1). Histopathology included 5 adenocarcinomas and 10 squamous-cell carcinomas. Resection margins were clear in 10 patients. The median follow-up time was 19 months (range: 3.5–53.4 months). Before radiation therapy commenced, delay in chemotherapy occurred in 20% of patients, and dose reduction was required in 13.3%. During the concurrent chemoradiation therapy phase, 20% of the patients experienced chemotherapy delay, and 6.6% experienced dose reduction. No patient experienced treatment-related acute and chronic esophagitis above grade 2. Disease recurred in 40% of the patients (6/15), and median time to relapse was 24 months. No tumour recurred at the anastomotic site. The median dfs was 23 months, and the median os was 21 months.

Conclusions

Extended-volume external-beam rt encompassing the tumour bed and the anastomotic site is feasible and safe for high-risk T3–4, N0–1 esophageal cancer patients after esophagectomy.     

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.     

Stereotactic hypofractionated radiation therapy for stage I non-small cell lung cancer

We reviewed our initial institutional experience with the use of stereotactic hypofractionated radiation therapy (SFRT) in patients with stage I non-small cell lung cancer (NSCLC). Thirty patients with inoperable stage I non-small cell lung cancer due to a severe chronic obstructive pulmonary disease (COPD) and/or chronic heart disease (Eastern Cooperative Oncology Group (ECOG) performance status of 0-2) were treated between December 2000 and October 2003 with SFRT in curative intent. Infiltration of locoregional lymph nodes and distant metastases were ruled out by computerized tomography (CT) scan of the brain, thorax, and abdomen, and by whole body FDG-positron emission tomography scan in all patients. Total RT doses ranged from 24.0 to 37.5 Gy, given in 3-5 fractions to the 60% isodose encompassing the planning target volume. Immobilization was carried out by a vacuum couch and a low-pressure foil. The clinical target volume was the tumor as it appeared in lung windowing on lung CT scan. Organ movements (caused by breathing; range, 6-22 mm) and reproducibility of patient positioning in the couch (range, 3-12 mm) were calculated by sequential CT and orthogonal films. The individual values were taken into account as a safety margin for the definition of the planning target volume (PTV). The median follow-up of living patients is 18 months (range, 6-38 months). As maximum response, there were 10 (33%) complete responses (CRs) and 14 (47%) partial responses (PRs), resulting in a total response rate of 80%. Stable disease was observed in 6 (20%) patients, while no patient experienced progressive disease. During follow-up, 2 (7%) local recurrences were observed (after 17 and 18 months, respectively). Of 5 (17%) patients who developed distant metastasis, 1 patient developed it in liver (3 months), another one in brain (6 months), and another one in the lung (36 months), while 2 patients developed it in mediastinal lymph nodes (after 8, and 11 months, respectively) only. Of 9 (30%) patients who have died, only 3 (10%) died of cancer, while 6 (20%) died of cancer-unrelated or unknown causes. Acute side effects were mild and affected 9 (33%) patients during the RT course (fatigue being the most frequent one in 6 patients). There were 22 acute events occurring in 19 (63%) patients during the first 3 months post-SFRT, the most frequent one being pneumonitis observed in 14 (46%) patients. However, there was only one (3%) grade 3 acute toxicity and no patient experienced greater than grade 3 toxicity during this study. One (3%) patient experienced rib fracture as the late event. SFRT is a feasible and safe treatment method in inoperable patients with stage I NSCLC having reduced lung capacity. Longer follow-up is necessary to get robust data on late toxicity as well as survival.     

放疗联合TP方案化疗综合治疗食管癌100例临床分析

目的:探讨食管癌放疗加TP方案化疗综合治疗的可行性和近期疗效.方法: 200例诊断为中晚期食道癌患者随机分组,综合治疗组应用放疗加化疗100例:紫杉醇135mg/m2静滴,d1,DDP30mg/m2,静滴,d1-3,休息1周后采用6MV X射线常规分割,前后对穿和等中心斜野照射.DT2Gy/次,5次/周,总量DT60-70Gy,6-7周.单纯放射治疗组100例,放疗方法同综合组.结果: 吞咽症状、临床改善情况:综合组为88%,单放组为68.0%,两组差异有显著性意义(P<0.05).近期疗效: 综合组为89.1%,单放组为67.0%,(P<0.05).放射治疗和药物的不良反应:综合组略高于单放组,但耐受.生存率:综合组1、2、3年生存率分别为63%、50%、39%较单放组54.0%、42%、30%为高.P<0.05. 结论: 放射治疗加TP化疗综合组疗效优于单放组,值得临床研究.     

Clinical results of concurrent chemoradiation therapy for primary highly advanced esophageal cancer

Clinical results after non-curative resection of highly advanced esophageal cancer are extremely poor. We administered concurrent chemoradiation therapy (CRT) as a multidisciplinary therapy in cases of highly advanced esophageal cancer for which non-curative resection is expected. The efficacy rate of the therapy was 59.4%, and the 3-year-survival rate 10.2%. A life-prolonging effect (the 3-year survival being 17.9%) was observed in the effective cases. Our future aim is to establish a safer, more reliable and cost-effective therapy by estimating the degree of efficacy before administration of CRT and then selecting cases suitable for CRT.     

Preoperative therapy for esophageal cancer: a randomized comparison of chemotherapy versus radiation therapy.

Ninety-six patients with operable epidermoid cancer of the esophagus were entered into a phase III, random assignment study designed to compare the efficacy of two preoperative approaches (chemotherapy [CT] or radiation therapy [RT]). Major study end points were objective response rates, surgical outcome, and recurrence pattern. Patients were randomly assigned to receive either two cycles of cisplatin, vindesine, and bleomycin or 55 Gy of radiation before a planned surgical procedure. Postoperative crossover therapy (radiation to those receiving preoperative CT and vice versa) was given to patients with T3Nany or unresectable tumors. Objective response rates of the primary tumor to preoperative therapy were similar (RT 64%, CT 55%), as were operability rates (RT 77%, CT 75%), resection rates (RT 65%, CT 58%), and operative mortality (RT 13.5%, CT 11.1%). Significantly higher doses of CT could be administered when CT was given as initial therapy, rather than after RT/surgery. Local failure or persistence occurred in 33% of operable patients. The median survival for all patients was 11 months; 20% remain alive without disease (median follow-up, 34 months). Because of the crossover design, it was not possible to analyze survival according to the preoperative therapy arm alone. This study suggests that since CT is as effective in treating local tumor as RT, but can also potentially treat systemic disease, investigational programs using CT before surgery as part of initial treatment for localized esophageal cancer should continue. However, if a significant impact on overall survival is to be achieved, more effective chemotherapy regimens or schedules need to be identified. Outside of carefully designed clinical trials, surgery alone or radiation alone remain standard therapy.     

乳腺癌保乳术后放疗疗效和美观效果

目的　观察乳腺癌保乳术后放疗的疗效和美观效果。方法　保乳术后全乳外照射和瘤床加量共10 9例,79例除应用高剂量率插植技术[T1期肿瘤用单排插植,针距为1.5cm ,T2期以上肿瘤用双排或三排插植;针距间单次剂量(DB) 10～12Gy ,靶区周边剂量为85 %DB]外,其中4 8例还经组织间插植加量放疗;30例除采用电子线常规外照射15Gy外,其中2 7例还经电子线外照加量放疗。全乳照射应用6MV直线加速器,采用双切线半野照射技术,靶区剂量为4 5～5 2Gy(平均4 8.6Gy)。采用医生评分与患者问卷方法评价美观效果。结果　5年生存率为93.8% ,局部复发率为6 .5 %。全组无放射性溃疡发生,5例出现位于插植针孔周围急性皮肤炎症。在经临床随访体检的75例中,医生打分和患者自评满意度为优的比例分别占87%和81% (P >0 .0 5 )。两组满意度医生总评为优的患者比例分别为81.2 %和85 .2 % (P >0 .0 5 )。结论　乳腺癌保乳术后放疗可降低术后复发率,并发症少。不同的瘤床加量放疗方法不影响美观满意度。     

External radiation therapy of stage I cancer of the endometrium: a need for reappraisal of this adjunctive modality

One hundred and eighty-five patients with Stage I cancer of the endometrium were irradiated preoperatively. All were irradiated to the whole pelvis by external beam only using supermegavoltage apparati. The total mid-pelvis dose ranged from 4500 cGy/5 weeks to 5500 cGy/6 1/2 weeks. Surgery followed usually in 6 weeks. Complications were minimal. Disease-free survival at Stage IA was 92.4% 5-year, 87.7% 10-year; Stage IB was 83.5% 5-year, 74.6% 10-year. Prognosis was related to stage, grade, depth of myometrial penetration, the presence of "residual" tumor at hysterectomy. External beam preoperative irradiation is recommended for all Stage I patients; Stage IB with higher grade pathology should have intracavitary irradiation supplemental to the external irradiation.     

Necessary radiological items for radiation therapy of esophageal cancer

Necessary items for radiation therapy of an esophageal cancer are discussed in detail. These radiological items can be dissolved through the radiological findings by use of the fine double contrast method of treating the esophagus. One method is to dissolve the infiltrative depth of the esophageal cancer; the other is the radiological diagnostic method to dissolve the effect of the radiation therapy on the esophageal cancer. In fact, regarding the former, the classification of the X-ray type is essential and depends upon the infiltrative depth of the cancer and, for the latter, the radiological findings before and after irradiation must be compared.