Masao Murakami

Reirradiation for locally recurrent lung cancer previously treated with radiation therapy

PURPOSEnLocal recurrence of lung cancer after previous external beam irradiation poses some problems for subsequent management. We retrospectively reviewed our series of patients with local recurrence of lung cancer to evaluate the efficacy and safety of reirradiation.nnnPATIENTS AND METHODSnBetween 1979 and 2000, 34 patients with local recurrence of lung cancer were retreated with external radiation. There were 29 males and 5 females ranging in age from 38 to 85 years (median: 69 years). At the time of reirradiation, the clinical stage was I or II in 2 patients, IIIa in 5 patients, IIIb in 14 patients, and IV in 13 patients. Reirradiation was performed in 18 patients with the aim of achieving a cure or prolongation of survival (radical treatment), while 16 patients were treated for improvement of their symptoms (symptomatic treatment).nnnRESULTSnThe median interval between the initial radiation therapy and reirradiation was 23 months, with a range of 5 to 87 months. The dose of initial irradiation delivered to the tumor ranged from 30 to 80 Gy (median: 60 Gy) in 1.5--2.0-Gy fractions per day. During reirradiation, it ranged from 10 to 70 Gy (median: 50 Gy) in 1.8--3.0-Gy fractions per day. The cumulative dose delivered to the tumor by treatments of both initial and second irradiation ranged from 56.5 to 150 Gy (median: 110 Gy). A response was observed in 14 out of 18 patients given radical treatment (complete response, 6; partial response, 8). Twelve of the 16 patients (75%) given symptomatic treatment also showed a symptomatic benefit. The overall survival rate after reirradiation was 43% at 1 year and 27% at 2 years, with a median survival time of 8 months. The median survival time after radical treatment was 15 months, with a range of 3 to 58 months, whereas that after symptomatic treatment was 3 months, with a range of 1 to 14 months. Six long-term survivors lived for more than 20 months. Reirradiation-induced toxicity included symptomatic radiation pneumonitis in 19 patients and symptomatic radiation esophagitis in 6 patients. These toxicities were not fatal, and radiation myelopathy was not caused by reirradiation.nnnCONCLUSIONnBased on this study, external beam reirradiation can achieve satisfactory results for local recurrence of lung cancer provided that attention is paid to the possible hazards.

The efficacy of conventional radiation therapy in the management of pituitary adenoma

PURPOSEnTo evaluate the efficacy of conventional radiotherapy for reducing tumor size and endocrine hypersecretion of pituitary adenomas.nnnMETHODS AND MATERIALSnWe reviewed the records of 91 patients with pituitary adenoma, who were first treated between 1969 and 1994 and had been followed for more than 2 years (median, 8.2 years.) Of these patients, 86 had received postoperative radiotherapy, and 5 had received radiotherapy alone. The median total dose was 51 Gy. Clinical symptoms related to mass effects or endocrine hypersecretion were assessed. The efficacy of radiotherapy was evaluated before treatment and during the follow-up period (1-14 years; median, 3 years) by estimating tumor size on computed tomography or magnetic resonance imaging in 56 patients, as well as by endocrine testing in the 22 patients who had secreting adenomas. Local control rate, prognostic factors, and side effects were analyzed.nnnRESULTSnMass-effect symptoms improved in 72% and 79% of patients who had such symptoms due to nonsecreting adenomas and secreting adenomas, respectively. Symptoms of endocrine hypersecretion abated in 67% of patients who had such symptoms. Excessive hormone levels normalized in 74% of patients who showed endocrine hypersecretions. The greatest size reduction was seen 3 years after the completion of radiotherapy (24% CR, 62% PR, 12% NC, and 3% PD in nonsecreting adenomas, and 32% CR, 36% PR, 27% NC, and 5% PD in secreting adenomas). Three patients with secreting adenomas (2 with prolactinoma and 1 with Cushings disease) showed a mismatch between reduction in tumor size and normalization of endocrine hypersecretion. The 10-year local control rates were 98%, 85%, 83%, and 67% for nonsecreting adenoma, growth-hormone-secreting adenoma, prolactinoma, and Cushings disease, respectively. Univariate analyses showed that disease type and radiation field size were significant prognostic factors. Brain necrosis occurred in 1 patient who received a 60-Gy dose of irradiation.nnnCONCLUSIONnWe conclude that conventional external radiotherapy with 50 Gy is safe and sufficient to control pituitary adenoma. Careful observation is required in the management of secreting adenomas because the effects on tumor size and endocrine hypersecretion may be mismatched in some secreting adenomas.

COMPARISON BETWEEN CHEMORADIATION PROTOCOL INTENDED FOR ORGAN PRESERVATION AND CONVENTIONAL SURGERY FOR CLINICAL T1-T2 ESOPHAGEAL CARCINOMA

PURPOSEnThis retrospective study was designed to compare treatment results of the chemoradiation protocol with conventional surgery for thoracic T1-T2 esophageal squamous cell carcinoma.nnnMETHODS AND MATERIALSnSixty-six patients with esophageal carcinoma, clinically diagnosed as T1 (tumor invading lamina propria or submucosa) or T2 (tumor invading muscularis propria) were treated for 12 consecutive years, from July 1986 to January 1998. The conventional surgery group included 30 patients who underwent esophagectomy with regional lymph node dissection. Twenty-one of them received postoperative radiotherapy. Thirty-six patients were assigned to the chemoradiation protocol, consisting of neoadjuvant chemoradiotherapy (44 Gy; CDDP: 60 mg/m2, day 1, bolus; 5-FU: 400 mg/m2, day 1-4, continuous), followed by either definitive radiotherapy with high-dose-rate intraluminal brachytherapy (total 70 Gy) for responders or surgery for nonresponders as in the conventional surgery group. Surgical candidates in both groups received intraoperative radiotherapy for abdominal lymphatics since 1991.nnnRESULTSnIn the protocol group, 4 patients underwent radical surgery after neoadjuvant chemoradiotherapy, and the remaining 32 underwent definitive chemoradiotherapy. Local control rates at 1 and 3 years were 85% and 70% in the T1/protocol group versus 91% and 80% in the T1/surgery group, and 83% and 83% in the T2/protocol group versus 94% and 80% in the T2/surgery group, respectively. There was no statistical significance. Overall 1- and 3-year survival rates were 100% and 83% in the T1/protocol group versus 82% and 72% in the T1/surgery group (p = 0.36), and 100% and 51% in the T2/protocol group, versus 95% and 68% in the T2/surgery group p = 0.61), respectively. There was no treatment-related mortality in either group. The rates of esophageal conservation were 92% in the T1/protocol group and 58% in the T2/protocol group.nnnCONCLUSIONnThe chemoradiation protocol can result in comparable survival with conventional surgery for patients with T1-T2 esophageal carcinoma. A randomized trial between definitive chemoradiotherapy and surgery is required.

Neoadjuvant concurrent chemoradiotherapy followed by definitive high-dose radiotherapy or surgery for operable thoracic esophageal carcinoma

PURPOSEnA prospective clinical trial was undertaken to investigate the feasibility of concurrent chemoradiotherapy for esophageal carcinomas.nnnMATERIALS AND METHODSnBetween June 1989 and May 1996, forty patients with operable squamous cell carcinoma of the thoracic esophagus (Stage 0 to III: UICC 1987), ages 45 to 78 years (mean: 64), were enrolled in a study of neoadjuvant concurrent chemoradiotherapy followed by definitive high-dose radiotherapy (CRT group) or surgery (CRT-S group). Neoadjuvant chemoradiotherapy consisted of 44 Gy in 40 fractions for 4 weeks (2.2 Gy/2 Fr/day) through 10-MVX rays, with 2 courses of cisplatin (80-100 mg/body, mean: 60 mg/m2, Day 1, bolus injection) and 5-fluorouracil (500-1000 mg/body/day, mean: 400 mg/m2, Days 1-4, continuous infusion). After completion of neoadjuvant chemoradiotherapy, an intermediate clinical response was assessed by barium swallow, esophagoscopy with/without biopsy, EUS in most cases, thoracic and upper abdominal CT scan, and cervical US. Definitive chemoradiotherapy was performed in patients when regression of more than 75% was evident (CRT Group), and esophageal resection was indicated in those who remained at less than 75% (CRT-S Group). In CRT Group, a cumulative dose of 60-70 Gy for Tis, T1 and 65-75 Gy for T2-T4 tumor with high-dose-rate intraluminal brachytherapy and a total of 3 courses of chemotherapy were planned. In CRT-S Group, intraoperative radiotherapy for abdominal lymphatic system and postoperative supraclavicular irradiation were added.nnnRESULTSnAt the time of intermediate assessment, complete response (CR) was observed in 16 patients, a partial response (PR) in 22, and no change (NC) in 2. Thirty responding patients (CR, 16; PR, 14) entered the CRT Group, and 10 nonresponding patients (PR, 8; NC, 2) were followed by surgery (CRT-S Group). Radiotherapy was completed satisfactorily, but chemotherapy was suspended in 26 patients (65%) because of acute toxicity. Clinical CR rate at the completion of treatment showed 90% in CRT Group, and pathologic CR rate 10% in CRT-S Group. The overall median survival was 45 months, survival at 1, 2, and 3 years being 100%, 72%, and 56%, respectively. Local-regional failure was observed in 7 patients (all in CRT Group), distant failure in 6 (3 in CRT Group, 3 in CRT-S Group) and local-regional with distant failure in 1 (CRT Group). Four patients with local-regional recurrence in the CRT Group were salvaged by surgery. Overall survival at 2 and 3 years for CRT vs. CRT-S Group was 72%, 64% vs. 75%, 38%, respectively. No treatment-related mortality was observed. The rate of the esophagus conservation was 65% (Stage 0: 1 of 1, 100%; Stage I: 11 of 12, 92%; Stage II: 8 of 17, 47%; Stage III: 6 of 10, 60%).nnnCONCLUSIONnOur results demonstrated that almost all early disease (Stage 0-I) and about half of advanced disease (Stage II-III) could be conserved, their esophagus treated by the multidisciplinary approach centering on high-dose radiotherapy and concurrent chemotherapy.

Carmofur-induced leukoencephalopathy: MRI

Carmofur, a derivative of 5-fluorouracil, has recently been noted to have an infrequent but serious association with leukoencephalopathy. To our knowledge, there has been no report of early MRI findings in this leukoencephalopathy. We describe a case in which diffuse high signal intensity of the entire cerebral white matter, including the corpus callosum, was seen on T2-weighted magnetic resonance images. Although similar findings can be seen in many other diseases, carmofur-induced leukoencephalopathy should be suspected in a patient treated with carmofur. It is important to know the clinical and MRI characteristics of this condition, for early diagnosis and better prognosis.

Mismatched clinicopathological response after concurrent chemoradiotherapy for thoracic esophageal cancer

We have been treating patients with operable thoracic esophageal cancer according to our own protocol. It includes the initial concurrent chemoradiotherapy (CRT) followed by continuous CRT or surgery. Patients with good response to initial chemoradiotherapy were allowed to continue chemoradiotherapy, whereas the others were treated with surgery. However, there were two cases which showed discrepancies in the clinicopathological response. Both patients received initial chemoradiotherapy, including two courses of cisplatin (100-120 mg), 5-fluorouracil (750-1000 mg for 4 days) and radiation (44-50 Gy). On completion of the initial chemoradiotherapy, all diagnostic imaging modalities including barium swallow, esophagoscopy, endoscopic ultrasonography and thoracic computed tomography strongly implicated residual tumor with a reduction rate of 40-50%. The patients underwent radical esophagectomy 15-20 days after initial chemoradiotherapy. Pathological specimens only revealed thickening of the esophageal wall due to inflammatory change without residual carcinoma. These facts suggest the current limitations of diagnostic images in evaluating the response to chemoradiotherapy.