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Biomedical subjects

N C Choi

Publications and source records attributed to N C Choi.

At least 37 records · Page 2Linked to original sources

Neoadjuvant chemotherapy and radiotherapy followed by surgery in stage IIIA non-small-cell carcinoma of the lung: report of a Cancer and Leukemia Group B phase II study.

PURPOSE: This phase II trial was designed to evaluate the feasibility, toxicity, response rates, and survival for neoadjuvant chemotherapy and radiotherapy (RT) followed by surgical resection in newly diagnosed patients with surgically staged IIIA non-small-cell lung carcinoma (NSCLC). PATIENTS AND METHODS: Previously untreated patients with NSCLC underwent bronchoscopy, chest and abdominal computed tomography (CT), bone scan, and surgical staging of the mediastinum. Neoadjuvant treatment consisted of concurrent chemotherapy and RT. Patients then underwent surgical resection, which was followed in turn by additional chemotherapy and RT. Chemotherapy included cisplatin 100 mg/m2 on days 1 and 29, vinblastine 3 mg/m2 on days 1 and 3 and 29 and 31, and fluorouracil (5-FU) 30 mg/kg/d by infusion on days 1 to 3 and 29 to 31 (FVP). RT began on day 1 and included 3,000 cGy in 15 fractions. Surgery took place on day 55, and one more cycle of chemotherapy and an additional 3,000 cGy of RT began on day 85. RESULTS: Forty-one eligible patients (median follow-up, 53 months) were studied. N2 disease was present in 80%, whereas 20% had T3N0 or T3N1 lesions. Response to neoadjuvant chemotherapy and RT included no complete responses (CR), 21 (51%) partial responses (PR) or regressions, 19 (46%) stable disease (SD), and one (2%) progressive disease (PD). Thirty-one patients underwent surgery, and 25 were resected. In four of the 25 resection specimens, no viable tumor was present, whereas in three of the six unresectable patients, extensive biopsy results demonstrated only necrotic tumor. The maximum response achieved using all protocol treatment was 27 (66%) CRs, seven (17%) PRs or regression, six (15%) SDs, and one (2%) PD. Toxicity was substantial and primarily hematologic. There were six (15%) treatment-related deaths, which included three perioperative deaths and three chemotherapy-related toxicity deaths. The Kaplan-Meier curve indicated a 1-year survival of 58% and a median survival of 15.5 months. Nine patients (22%) remain disease-free. CONCLUSIONS: There was a reasonably high rate of PR associated with concurrent neoadjuvant chemotherapy and RT, and a high percentage of patients who ultimately were rendered completely disease-free. However, treatment-related morbidity and mortality was common. Median survival seemed to be only modestly improved beyond that achieved with less intensive means of treatment. However, a group has emerged of patients who enjoy prolonged disease-free survival and possible cure.

Adult↗

A pilot study of neoadjuvant chemotherapy with 5-fluorouracil and cisplatin with surgical resection and postoperative radiation therapy and/or chemotherapy in adenocarcinoma of the esophagus.

Fifteen patients with potentially resectable adenocarcinoma of the esophagus were treated with two cycles of preoperative chemotherapy with 5-fluorouracil (5-FU) and cisplatin (DDP). Response to chemotherapy was evaluated by comparative barium swallow, computerized chest tomography, esophagoscopy, and change in clinical symptomatology. Eleven patients (73%) were resected, two (13%) were explored and found inoperable, and two (13%) were not subjected to surgery (one because of death related to toxicity and one due to progressive disease). Ten of eleven patients (91%) had gross residual tumor. One patient (9%) had residual microscopic disease only. One patient (7%) had complete clinical responses (CCR), five (33%) had partial clinical response (PCR), and nine (60%) had no response (NR). Five of 15 patients (or 45% of resected patients) remain free of disease. Median survival time was 18.47 months for all patients and 23.83 months for resected patients.

Adenocarcinoma↗

Effect of postoperative radiotherapy on changes in pulmonary function in patients with stage II and IIIA lung carcinoma.

To assess the pulmonary tolerance to postoperative radiotherapy (RT) in patients with resected lung carcinoma, a prospective study was begun in January 1977, which consisted of (a) initial pulmonary function test (PFT) and arterial blood gases (ABG) at 1 month after surgery, and before beginning of postoperative RT, and (b) follow-up PFT and ABG 1 year after postoperative RT and then every year thereafter. As of December 1987, 137 patients have been enrolled into this study, and 71 patients who were free of recurrence were subjected to the follow-up PFT and ABG. The remaining 66 patients were unable to complete the follow-up studies because of recurrent carcinoma in 60, refusal to participate in the study in 5 patients even in the absence of significant respiratory symptoms, and progressive asbestos-related pleural thickening in 1 patient. The patient characteristics were as follows: Age ranged from 27 to 79 years with the median of 59 years; sex ratio was 1.4 to 1 for male to female; surgical procedures included lobectomy in 49 and pneumonectomy in 22 patients; tumor extent consisted of Stages T1-T2N1M0 in 44, T1-T2N2M0 in 9, and T3N0-N2M0 in 18 patients, respectively. Histologic types included squamous cell carcinoma in 26, adenocarcinoma in 42, small cell carcinoma in 1, and large cell carcinoma in 2 patients. Target volume for RT included the ipsilateral hilum, the mediastinum, and the thoracic inlet including both supraclavicular fossae. A total dose of 54 Gy was delivered in 1.8 Gy of daily fractions, 5 days per week over a period of 6 weeks. Contrary to expectation, there were minor changes in PFT indices in both lobectomy and pneumonectomy patients. The follow-up PFT in the lobectomy group showed small -3% to +2% changes in mean values of ventilatory indices, lung volume, and ABG. The follow-up PFT in the pneumonectomy group also showed small -9% to +13% changes in mean values of ventilatory indices, lung volume, and ABG. Sixteen patients have had more than one PFT during the follow-up period (2 years to 10 years), and there was no significant long term adverse effect of RT on PFT in this subset of patients. Lung scans assessing regional function, which were available in six patients, were not helpful in predicting changes in PFT indices as a result of postoperative RT.

Adult↗

Importance of radiation dose in achieving improved loco-regional tumor control in limited stage small-cell lung carcinoma: an update.

Between 1974 and 1986, 576 patients (284 limited and 292 extensive stages) were treated at this institution. To keep multiagent chemotherapy (CT) at a uniform intensity, patients who received (a) combined modality approach of both multiagent chemotherapy and thoracic radiotherapy (RT) and (b) greater than or equal to 3 cycles of multiagent chemotherapy (greater than or equal to 3 drugs), were chosen for this analysis. Out of 284 patients with limited Stage small-cell lung carcinoma, there were 154 such patients who met these strict criteria, and the treatment methods for the remaining 130 patients were as follows: (a) chemotherapy alone with radiotherapy reserved for local failure (47 pts); (b) radiotherapy alone (20 pts); (c) surgery +/- adjuvant chemotherapy or radiotherapy (37 pts); (d) modified chemotherapy plus radiotherapy (26 pts). During the 12-year period, the therapeutic factors have evolved. Radiation-dose was increased from 30-40 Gy (time dose fractionation 49-66) in 1974-1977 to 44-52 Gy (time dose fractionation 73-86) in 1978-1986. The target volume for radiotherapy included the primary lesion with a 2-cm margin of normal lung and the mediastinum. Chemotherapy program also evolved from COP, CAV (1974-1977) to MACC, VCE-VCA, PCE-ACE (1978-1986). Fifty of 154 patients (32%) developed loco-regional recurrence (infield failure) and 98% (49/50) of these patients exhibited this by 2.5 years. Survival data of 154 patients were as follows: (a) Median survival time (MST) was 12 M; (b) actuarial survival rates at 2 and 5 years were 21% and 8%, respectively. Fifty percent of these patients died within 12 months (MST 12 M) and were not exposed to the full length of the risk period for loco-regional failure. To take into account the duration of exposure to the risk period, actuarial method was employed to measure the probability of loco-regional failure. Loco-regional failure rates at 2.5 years were 37%, 39%, 49%, 79%, and 84% for 50 Gy, 45 Gy, 40 Gy, 35 Gy, and 30 Gy, respectively. The difference between the recurrence rates of 37% and 79% by 50 Gy and 35 Gy was statistically significant, p less than 0.05. Although the recurrence rates of 37% and 49% by 50 Gy and 40 Gy were not statistically different, there was a strong trend of a better control rate of loco-regional carcinoma by higher radiation doses. The time to recurrence seems also shorter with lower radiation-dose than that of higher radiation doses.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Preoperative chemotherapy, surgical resection, and selective postoperative therapy for squamous cell carcinoma of the esophagus.

In an attempt to improve on the long-term survival rate of patients with esophageal squamous cell carcinoma, we designed a study in which treatment included preoperative chemotherapy with fluorouracil and cisplatin, surgical resection, and selective postoperative chemotherapy or radiation therapy. Between 1981 and 1986, 35 patients with potentially resectable lesions were entered into the study. After chemotherapy, 13 of 35 patients (37%) had a complete clinical response, 7 (20%) had a partial response, and 15 (43%) had no response. One patient sustained a serious toxic reaction (renal failure). Twenty-seven patients underwent surgical resection, with 1 hospital death (3.7%). Selective postoperative radiotherapy or chemotherapy was administered to 69%. The actuarial survival of all resected patients at 42 months was 54% (standard error, 10%). Multivariate analysis showed significant factors associated with 3-year survival were: (1) complete clinical response to chemotherapy; (2) absence of wall penetration in the specimen; and (3) microscopic or no disease in the specimen. We conclude that this multimodality treatment method improves the intermediate-term survival of patients with squamous cell carcinoma of the esophagus.

Antineoplastic Combined Chemotherapy Protocols↗

Small cell carcinoma of the lung. A progress report of 15 years' experience.

To assess the results of therapeutic advances in the treatment of small cell carcinoma of the lung (SCCL) achieved during the past 15-year period at a single large institution, 508 patients treated between 1968 and 1982 were divided into two groups: 157 patients (66 in the category of limited-stage disease and 91 in the extensive-stage disease category) treated with low-dose small-volume radiotherapy (RT) (time dose fractionation [TDF] 49-66) and with cyclophosphamide alone or a COPP program during the first period of 7 years (1968-1974); 351 patients (180 in limited and 171 in extensive stage) treated with multidrug chemotherapy (CT) and high-dose large-volume RT (TDF 73-89) during the second period of 8 years (1975-1982). For patients with limited-stage cancer, 5-year actuarial survivals were 3% versus 7% for the periods 1968-1974 versus 1975-1982, respectively, P less than 0.01. For patients with extensive-stage cancer, the median survival time (MST) and 2-year actuarial survivals were 5 months and 2% versus 7 months and 4% for the periods 1968-1974 versus 1975-1982, respectively. To evaluate the outcome of a contemporary approach, i.e., CT alone, with RT reserved for locoregional failure, 180 patients with limited-stage cancer who were treated (1975-1982) were further analyzed for MST, 2- and 5-year actuarial survival figures, and local-tumor control rates according to the therapeutic approaches employed: CT + RT (112); CT alone (36); RT alone (17); and surgery (S) +/- CT +/- RT (15). Although the 36 patients in CT alone seems a small number, 17 of the 36 patients were enrolled in this approach in 1981-1982, reflecting a shift of emphasis from RT to CT. The MST and 2-year actuarial survival figures were 11 months and 0% versus 13 months and 21% for CT alone versus CT + RT respectively, P less than 0.05. CT + RT achieved a 5-year cure rate of 8%. S +/- CT +/- RT or RT alone also achieved 5-year cure rates of 8% and 10.5%, respectively, in selected subsets of patients. Local relapse rates were 80% (29/36) versus 25% (28/112) for CT alone versus CT + RT. These data emphasize the importance of thoracic RT given at the early phase of treatment to improve long-term survival for patients with limited-stage SCCL.

Actuarial Analysis↗

Accelerated radiotherapy followed by chemotherapy for locally recurrent small-cell carcinoma of the lung. A phase II study of Cancer and Leukemia Group B.

Recurrent or persistent small-cell carcinoma of the lung (SCCL) after chemotherapy (CT) alone has shown a poor response to conventional salvage radiotherapy (RT). Accelerated RT is judged more effective than conventional RT for rapidly growing tumors such as SCCL. The objectives of this study were: to determine the tolerability of accelerated RT; and to test the ability of accelerated RT plus CT to achieve local tumor control (LTC) of SCCL recurrent after CT. Patients whose localized tumor was not controlled were selected from Arm III of the Cancer and Leukemia Group B (CALGB) protocol 8083 (Proc. ASCO 2:230, 1984) as eligible for this study. The program of accelerated RT consisted of the delivery of 50.1 Gray (Gy) in 30 fractions over a period of 21 days to the chest. New chemotherapy different from the first began 2 weeks after the completion of RT and was repeated every 3 weeks for 18 months (M). Of 29 potentially eligible patients with locally recurrent SCCL after the first line CT alone from Arm III of the CALBG protocol 8083, 12 were enrolled initially in this study. The analysis of LTC included 11 patients excluding one patient who died 4 weeks after the start of RT from liver metastases. The LTC achieved was as follow: complete remission in 8/11 (72%) and partial remission in 3/11 patients. None of the patients was converted to CR by subsequent chemotherapy. Survival ranged from 2 to 20 M, with a median survival time of 6 M. Tolerance to the subsequent CT, normal tissue reaction to accelerated RT, and the theoretical advantage of accelerated RT over conventional RT for SCCL were evaluated.

Aged↗

Intradural spinal metastases in patients with posterior fossa brain metastases from various primary cancers.

Intradural spinal metastases (ISM) are rare and primarily found associated with certain types of brain tumors like medulloblastoma. Their association with metastases to the brain has been recently described and seems to occur more frequently in posterior fossa lesions. We reviewed patients treated at Massachusetts General Hospital for posterior fossa brain metastases from various primary cancers, and evaluated the risk of concomitant or subsequent ISM. Of 104 patients, 10 developed ISM, with a 1-year actuarial risk of 25%. The risk was not significantly related to age, sex, histology, site of primary tumor or previous therapy. The study suggests that in patients with posterior fossa metastasis, particular attention should be paid to seeding via cerebrospinal fluid and drop metastases to the spinal cord.

Adenocarcinoma↗

Cytologically negative pericardial effusion complicating combined modality therapy for localized small-cell carcinoma of the lung.

A 17% frequency of cytologically negative pericardial effusion (CNPE), accompanied in some cases by tamponade, occurred a median of 12.6 months from the onset of treatment for localized small-cell carcinoma of the lung. CNPE was apparently caused by toxicity of radiation/chemotherapy treatment rather than recurrent cancer. The occurrence of CNPE does not appear to represent enhanced toxicity of immediate (as opposed to delayed) concurrent chemoradiotherapy, but may be a consequence of the superior survival status of patients treated in this way. The onset of chest pain and/or dyspnea associated with increase in cardiac silhouette and positive echocardiogram allowed accurate diagnosis. Each instance was relatively easily managed by catheter drainage, and, for some patients, with the addition of nonsteroidal antiinflammatory drugs. It is important to recognize the possibility that a radiation/chemotherapy-related syndrome of pericardial effusion/tamponade may occur so that early diagnosis can be made and the risk of fatal tamponade avoided.

Antineoplastic Agents↗

Radiation therapy alone or in combination with surgery in the treatment of carcinoma of the esophagus.

The role of radiation in the treatment of squamous cell carcinoma of the esophagus was examined in a review of 74 patients treated with curative intent between 1974 and 1981. Aspects studied included the pattern of failure, the use of radiation as a surgical adjuvant, achievement of palliation, and the presence of technical or clinical factors predicting for a better outcome. The group was divided into 9 patients irradiated after esophageal resection, 14 patients irradiated before resection, and 51 patients treated with radiation and no resection. Median and 2-year survival rates among 51 patients treated by radiation without esophagectomy were 8.8 months and 11%, whereas they were 9.7 months and 0% in patients treated by radiation followed by resection, and 9.5 months and 28% in patients undergoing resection followed by radiation. Local failures were suffered in 28/51 patients treated without esophagectomy with rates of 2/4, 7/10, 7/15, and 5/10 after 50-55 Gy, 55-60 Gy, 60-65 Gy, and 65-69 Gy, respectively. Although prognosis for patients presenting with unresectable disease remains poor, a somewhat better outcome may be expected in patients treated with postoperative radiation after potentially unfavorable resections. Other predictors include sex and disease stage.

Carcinoma, Squamous Cell↗

The risk of intradural spinal metastases in patients with brain metastases from bronchogenic carcinomas.

Intradural spinal metastases can develop following dissemination via the cerebrospinal fluid from various primary or secondary brain tumors. Since the risk of intradural spinal metastases has never been formally studied in patients with brain metastases, we reviewed patients with brain metastases from bronchogenic carcinomas and looked for the subsequent development of intradural spinal metastases. Of 160 consecutive patients, only 6 presented intradural spinal metastases, however none were among the 105 patients who had exclusively supratentorial metastases and all intradural spinal metastases were in patients who had lesions in the posterior fossa. In this group, the 1-year actuarial risk of having intradural spinal metastases was 21% (p less than .01 compared with patients who had supratentorial metastases). We could not find any other risk factor for intradural spinal metastases. Recommendations for the group of patients with increased risk of intradural spinal metastases are made.

Adult↗

Preoperative chemotherapy followed by surgery with possible postoperative radiotherapy in squamous cell carcinoma of the esophagus: evaluation of the chemotherapy component.

Twenty-four patients with squamous cell cancer of the esophagus were entered into a treatment protocol consisting of preoperative chemotherapy (CT), surgical resection (SR), and possible postoperative CT or radiation therapy (RT) beginning August 1981. CT consisted of two cycles of 5-fluorouracil, 1,000 mg/m2, by continuous intravenous infusion for 4 days and cisplatin, 100 mg/m2, on day 4 with mannitol-induced diuresis at 4-week intervals. Postoperatively, RT was administered when resection margins were minimal or if paraesophageal nodes were abnormal; the RT consisted of 5,000 to 5,400 cGy to the tumor area plus a 800- to 1,200-cGy boost to known abnormal tumor margins. Nineteen of 24 patients were resectable (79%). There was one SR death (5%). One of 22 had a normal barium swallow post-CT, no visible tumor at SR, and no pathologic evidence of any residual disease. There was complete radiologic and gross clinical disappearance of tumor post-CT or post-SR in ten of 22 patients (45%). Four of 22 (18%) had greater than or equal to 50% regression, and five of 22 (23%) had no response. Toxicity of CT was mild. Eight of 19 patients (42%) received RT, and six of 19 (32%) received CT postoperatively. Sixteen of 24 (67%) are alive with a median duration of observation of 9.5 months. Eight of 24 (33%) are dead, five of whom had not responded to preoperative CT. Ten of 14 responders are alive and disease free. The mean survival time for nonresponders was 6.70 months and for responders, 20.40 months, with the longest survivor disease free at 45 months.

Aged↗

Improved quality of life of patients with small-cell carcinoma of the lung by elective irradiation of the brain.

About 30% of all patients with small cell undifferentiated carcinoma of the lung will ultimately develop metastases in the brain. It is now well established that elective whole brain irradiation can prevent such metastases, although it does not increase survival time. However, we have found that such treatment does increase the quality of life for these patients. Those with limited disease can survive with a Karnofsky scale of more than 60 for a mean time of 10 months compared with 6 months for an equivalent group treated only when these brain metastases occur. We have also found that treating patients therapeutically does not insure success as 6/16 eventually relapsed in the brain. We conclude that elective brain irradiation in patients with small cell undifferentiated carcinoma of the lung who present with a limited disease is of value because the quality of life is improved significantly.

Brain Neoplasms↗