Biomedical subjects

Ritsuko Komaki

Publications and source records attributed to Ritsuko Komaki.

At least 55 records · Page 3Linked to original sources

PubMed2005

Intensity modulated radiation therapy and proton radiotherapy for non-small cell lung cancer.

Local failure of non-small-cell lung cancer (NSCLC) radiotherapy may cause continuous tumor seeding and death. Radiotherapy dose escalation has been shown to improve local control and survival. However, the toxicities associated with dose escalation are significant and limit the potential of dose escalation. Intensity modulated radiotherapy (IMRT) may have the potential to improve the therapeutic ratio for photon treatment of lung cancer by sparing surrounding normal tissues. However, low-dose exposure to normal lung and organ motion is a major concern. We have conducted several studies to address these issues and started clinical studies to evaluate the potential benefit of IMRT in patients with NSCLC. Proton radiotherapy may have greater potential to spare normal tissue and allow for further dose escalation and acceleration. We are conducting preclinical and clinical studies for imaging-guided proton radiotherapy in NSCLC. In this paper, we discuss the preliminary data, IMRT treatment guidelines, and ongoing studies for proton therapy in NSCLC.

Carcinoma, Non-Small-Cell Lung↗

PubMed2005

Preoperative chemoradiotherapy prior to esophagectomy in elderly patients is not associated with increased morbidity.

BACKGROUND: Preoperative chemotherapy and radiation therapy are often administered to patients with esophageal cancer. Despite an aging population, little data exist regarding feasibility of preoperative therapy in elderly patients. METHODS: Between January 1997 and December 2002, 312 consecutive patients underwent esophagectomy for esophageal cancer at our institution. Outcomes of patients 70 years old, who underwent preoperative therapy (n = 35; group II), were compared with those of patients who did not (n = 39; group I) and with those of patients younger than 70 years old who received preoperative therapy (n = 165; group III). RESULTS: The median age was 75 years old for group I and 72 years for group II (p < 0.001). The patients in group II were of more advanced clinical stage (p < 0.001). There were no differences in performance status, comorbidities, or preoperative symptoms between the two groups. Similar proportions of patients in the groups I and II underwent a transhiatal approach (52.5% vs 42.8%, p = not significant [NS]). Perioperative mortality for groups I and II was 0% and 3%, respectively (p = NS). Group II received more perioperative blood transfusions (71.4% vs 48.7%, p = 0.047). There were no differences in the rates of postoperative cardiac, pulmonary, neurologic, gastrointestinal, or anastomotic complications. Compared with group III, group II patients had higher rates of postoperative atrial arrhythmias (p = 0.013) and perioperative blood transfusions (p = 0.004). CONCLUSIONS: Elderly patients receiving preoperative therapy for esophageal cancer do not have an increased incidence of major postoperative complications. Elderly patients receiving preoperative therapy are more likely to develop postoperative atrial arrhythmias and require transfusion than younger patients.

Adenocarcinoma↗

PubMed2005

The evolution of treatment outcomes for resected stage IIIA non-small cell lung cancer over 16 years at a single institution.

OBJECTIVES: The effect of multimodality treatment including surgical intervention, chemotherapy, and radiation for potentially resectable stage IIIA non-small cell lung cancer in a practice setting remains to be defined. To determine which treatment factors are associated with improved survival, we evaluated outcomes for these patients at our institution over a 16-year period. METHODS: We surveyed our institutional pathology database from 1986 through 2001 for patients with resected pathologic stage IIIA (N2) non-small cell lung cancer. Three hundred fifty-three patients were confirmed to have appropriate pathologic staging and attempted complete resection. These patients were assessed by means of univariate and multivariable analysis for factors associated with long-term survival. Stage migration was estimated by using a classification based on nodal station involvement. RESULTS: Median potential follow-up was 132 months. During the study period, 3- and 5-year survival increased; preoperative staging improved, relatively more lobectomies and fewer pneumonectomies were performed, and multimodality treatment was used more frequently. The number of positive N2 nodal stations did not change over time (P = .14). Surgical intervention alone resulted in 3-year survival of 30%, and perioperative chemotherapy, radiation, or both increased 3-year survival to 38% (P = .004). Multivariable analysis showed that male sex (hazard ratio, 1.44; 95% confidence interval, 1.13-1.84; P = .003), more than 2 positive mediastinal nodal stations (hazard ratio, 1.73; 95% confidence interval, 1.16-2.57; P = .007), R1 or R2 resection (hazard ratio, 1.72; 95% confidence interval, 1.22-2.41; P = .002), lower or middle lobe tumor location (hazard ratio, 1.63; 95% confidence interval, 1.28-2.08; P < .001), and surgical intervention alone (hazard ratio, 1.59; 95% confidence interval, 1.23-2.04; P < .001) were independent predictors of poor survival. CONCLUSIONS: The use of multimodality therapy appears to contribute to improved outcomes over time in patients with resected stage IIIA (N2) non-small cell lung cancer.

Carcinoma, Non-Small-Cell Lung↗

PubMed2005

Patterns of care survey (PCS) in lung cancer: how well does current U.S. practice with chemotherapy in the non-metastatic setting follow the literature?

BACKGROUND: In LD-SCLC, combined modality therapy has emerged as the standard of practice in good performance status (PS) patients (pts). Pignon's meta-analysis [N Engl J Med 1992;327:1618-24] showed that combination chemotherapy (CT) and thoracic radiation (XRT) in LD-SCLC yielded an absolute 5.4% increase in 3-year survival versus chemotherapy alone. Concurrent chemoradiation upfront has generated the highest survival rates [Murray. J Clin Oncol 1993;11:336-44; Jeremic. J Clin Oncol 1996;15:893-900; Takada. J Clin Oncol 2002;20:3054-60]. In stage III NSCLC, multiple studies have shown therapeutic superiority for combination chemotherapy and XRT versus RT alone; and recent literature suggests a therapeutic advantage for concurrent chemoradiation versus chemotherapy followed by XRT [Curran. ASCO 2000;19:484a; Furuse. JCO 1999;17:2692-9; Zatloukal. ASCO 2002;A-1159]. Data are less secure regarding the role of chemotherapy in stage I and II NSCLC. MATERIAL AND METHODS: A stratified two-step cluster sampling technique was used for data collection. Five hundred and forty-one individuals diagnosed between 1998 and 1999 with lung cancer, either LD-SCLC or stages I-III NSCLC were sampled from 58 institutions featuring radiotherapy facilities, giving a weighted sample size (wss) of 42,335 patients. All pts had Karnofski performance status (KPS) >or=60. We determined the percentage who received chemotherapy; the nature of chemotherapy and its timing with respect to XRT. SUDAAN statistical software was used to allow the incorporation of the design elements and weights to reflect the relative contribution of each institution and each patient in the analysis RESULTS: Of 72 (wss=6138) pts with LD-SCLC, 100% received XRT and 95% received chemotherapy (CT); 66% received concurrent (con) CT and XRT, of whom 29% also received CT pre XRT; 22% received CT post XRT as well, and 23% received both: 63% received sequential CT-->XRT+/-con CT; and 38% received some CT after XRT. Fifty-two percent received cisplatin (DDP), and 38% received carboplatin (CBDCA); 73% received etoposide (VP-16), while 10% received paclitaxel. Of 469 pts (wss=36,197) with NSCLC, 52% received CT, including 30% with stage I disease, 48% with stage II NSCLC, 60% with stage III NSCLC, and 50% with unknown stage. Thirty-nine percent received sequential CT-->XRT+/-CT, of whom 49% received CT pre XRT only. Seventy-four percent received con CT and XRT; and 27% received posterior CT, of whom 84% also received con CT/XRT. Forty-five received some CT in the pre-op setting and 15% in the post-op setting. Twelve percent received DDP-based therapy, while only 13% and 7% received VP-16 or vincas, respectively; 67% received CBDCA. Seventy-two percent received taxanes, of whom 96% received paclitaxel. Gemcitabine was administered to 3% of NSCLC pts. CONCLUSIONS: Combined modality therapy is typically employed in the therapy of LD-SCLC and LA-NSCLC. The majority of those treated for SCLC receive concurrent CT/XRT, while nearly 3/4 of those treated with CT and XRT for LA-NSCLC received concurrent CT/XRT. Current practice in the US generally matches evidence-based literature, although a significant percentage of practitioners substitute CBDCA for DDP in both venues and use paclitaxel in lieu of vincas or etoposide in NSCLC.

Adult↗

PubMed2005

Mutagen sensitivity may predict lung protection by amifostine for patients with locally advanced non-small cell lung cancer treated by chemoradiotherapy.

Amifostine (AMF) has been shown to protect some normal tissues from acute effects of radiation therapy +/- chemotherapy. We enrolled 62 patients in a randomized study investigating the efficacy of AMF: 31 had concurrent chemoradiation for non-small cell lung cancer and 31 had the same treatment + AMF. AMF reduced the frequency and severity of esophagitis, pneumonitis, and neutropenic fever. We have tried to identify patients who get more benefit from AMF by checking their DNA repair capability of normal cells. It was hypothesized that DNA repair capacity from patients' lymphocytes damaged by bleomycin could predict their normal tissue sensitivity to chemoradiation and could be protected by AMF. Forty-six of the 62 patients provided pretreatment blood for assessment of mutagen sensitivity (MS) using a peripheral lymphocyte assay that infers DNA repair capacity from cellular damage remaining after in vitro mutagenic exposure and recovery. Bleomycin-induced chromosome breaks in 50 metaphases were counted and expressed as the mean number of breaks per cell. Patients with an average of more than one break/cell were deemed to exhibit the MS phenotype. Data analysis used Pearson's chi-square and Kaplan-Meier survival function estimates with Strata 8.2 statistical software. The Log-rank test was used to assess the equality of survival function using a P value of .05. Twelve patients (10 AMF, 2 control) exhibited the MS phenotype. The remaining 34 patients (13 AMF, 21 control) were considered to have normal DNA repair. There were no significant differences in overall survival, disease specific survival, or local control by MS. Those with high MS had shorter distant metastasis-free survival compared with low MS patients ( P = .029). There were no differences in severe esophagitis or neutropenic fever by MS. Both high and low MS patients from the control group developed severe lung fibrosis compared with five of 21 who had AMF ( P = .025). The incidence of grade 3/4 lung fibrosis was two of 10 with AMF compared with two of two in the control group ( P = .025) with higher MS. Higher MS was associated with shorter distant metastasis-free survival and more frequent grade 3/4 lung fibrosis. AMF reduced the incidence of grade 3/4 lung fibrosis among higher MS. These data suggest that MS might help identify subgroups of patients who could receive more benefit from AMF with respect to lung damage.

Adult↗

PubMed2004

Evaluation of internal lung motion for respiratory-gated radiotherapy using MRI: Part II-margin reduction of internal target volume.

PURPOSE: To analyze the relationship between lung motion and skin surface motion during respiration, determine the uncertainties and variability of such a relationship, and assess the potential of reducing internal target margin for gated radiotherapy. METHODS AND MATERIALS: Three healthy volunteers and four lung cancer patients were recruited in a prospective imaging study using MRI to track the internal lung and external skin motion during breathing. The relationship between the lung and skin motion was modeled using linear regression analysis. The slope of the linear fit and its confidence interval were analyzed for different lung locations, skin surface locations, and breathing patterns from separate imaging sessions. The margins of the internal target volume were calculated based on the residual lung motion during gating and its uncertainties from multiple treatment fractions for the gated treatment. RESULTS: The slope and confidence interval of the linear regression from the motion analysis were uniquely defined by the locations of the lung, skin surface, and breathing patterns. Statistically significant differences were observed among individuals and between different times of measurement. The normal free-breathing motion averaged from all volunteer and patient data was 13.4 +/- 7.4 mm along the superior-inferior (SI) direction and 6.9 +/- 2.6 mm along the anterior-posterior (AP) direction. With simulated respiratory gating, the average margin reduction was 5.5 +/- 4.8 mm and 1.6 +/- 1.0 mm, respectively, along the SI and AP directions (or 36% +/- 15% and 25% +/- 14%, respectively, relative to free-breathing motion). CONCLUSION: Because respiratory movement is rather complex, the relationship between the lung and skin surface motion is affected by many anatomic and physiologic factors. The reduction of internal target margin and efficacy of the free-breathing gating technique should be assessed for individual cases.

Adult↗

PubMed2004

Evaluation of internal lung motion for respiratory-gated radiotherapy using MRI: Part I--correlating internal lung motion with skin fiducial motion.

PURPOSE: To measure the internal lung motion due to respiration using magnetic resonance images (MRIs); to evaluate the correlation between lung motion and skin surface motion and the reliability of tracking lung motion with external fiducials. METHODS AND MATERIALS: An MRI protocol using fast gradient-echo sequences was developed to acquire dynamic cine images of the thoracoabdominal region along the axial, sagittal, and coronal planes. The subjects (3 healthy volunteers and 4 lung cancer patients) were instructed to perform normal or altered breathing during MRI. Lung vessels identified on MRI were used as anatomic landmarks for internal lung structures. From sagittal cine MRI scans, the positions of the lung vessels and skin surface were tracked and their movements measured. Correlation between the movements of the external markers and internal structures was then calculated and analyzed. RESULTS: Lung vessel motion in the superior-inferior (SI) direction correlated best with mid-upper abdominal skin surface movement (correlation coefficient, 0.89 +/- 0.09 and 0.87 +/- 0.23 for volunteers and patients, respectively). The anterior-posterior (AP) vessel motion generally correlated poorly with the skin surface movement, with marker placement on the upper chest yielding the strongest results (correlation coefficient, 0.72 +/- 0.23 and 0.44 +/- 0.27 for volunteers and patients, respectively). The strength of the correlation depended on the locations of the tracked vessels, locations of the skin surface, and subjects' breathing patterns. The best correlation was seen between the motion of an abdominal fiducial and SI lung motion. Significant intersubject variability was also observed. CONCLUSION: Movement of an external fiducial may not correlate fully with, or predict, internal lung motion. Effective monitoring of respiration may have to rely on a combination of multiple fiducials and other physiologic parameters, such as lung volume and/or air flow.

Adult↗

PubMed2004

Esophagectomy after concurrent chemoradiotherapy improves locoregional control in clinical stage II or III esophageal cancer patients.

PURPOSE: To evaluate the effect of surgical resection on the outcome of patients with clinical Stage II or III cancer of the esophagus treated with concurrent chemoradiotherapy. METHODS AND MATERIALS: A retrospective review of 132 consecutive patients with clinical Stage II or III esophageal cancer treated with concurrent chemoradiotherapy between January 1990 and December 1998 was performed. Of the 132 patients, 60 underwent esophagectomy 6-8 weeks after chemoradiotherapy. The median radiation dose was 50 Gy (range, 30-64.8 Gy) in the definitive chemoradiation group and 45 Gy (range, 30-50.4 Gy) in the chemoradiation plus esophagectomy group. RESULTS: Statistically significant differences were found between the two groups in median age, histologic subtype, tumor location, and number of patients with T4 disease. Patients who underwent definitive chemoradiotherapy were older (p = 0.0004) and more likely to have squamous cell carcinoma than adenocarcinoma (p <0.000), upper thoracic or cervical esophageal tumors (p <0.000), and T4 tumors (p = 0.024). Patients treated with chemoradiation plus esophagectomy had statistically significant superior 5-year loco-regional control (67.1% vs. 22.1%, p <0.000), disease-free survival (40.7% vs. 9.9%, p < 0.000), and 5-year overall survival (52.6% vs. 6.5%, p < 0.000) rates and median survival time (62 vs. 12 months) compared with patients treated with chemoradiotherapy only. However, no statistically significant difference was found in the rate of distant metastasis-free survival between the two groups (67.5% vs. 65.8%, p = 0.3). Surgical resection of the tumor was an independent predictor of improved locoregional control and overall survival in both univariate and multivariate analyses. To reduce the effect of the selection bias on the outcome, 34 patients in each group with matched pretreatment characteristics were compared. The results showed statistically significant better overall survival, disease-free survival, and locoregional control in favor of the chemoradiotherapy plus esophagectomy group. No statistically significant difference in distant metastasis-free survival was found in this subgroup analysis. CONCLUSIONS: Locoregional control was better in clinical Stage II or III esophageal cancer patients treated with concurrent chemoradiation plus esophagectomy. An improvement in survival occurred in the chemoradiation plus esophagectomy group, although this observation may have reflected selection bias. The results from this study suggest the need for a randomized trial to compare chemoradiation with or without esophagectomy in the treatment of cancer of the esophagus.

Adenocarcinoma↗

PubMed2004

Induction chemotherapy improved outcomes of patients with resectable esophageal cancer who received chemoradiotherapy followed by surgery.

PURPOSE: To investigate the effect of induction chemotherapy (CHT) before trimodality therapy on the outcome of patients with resectable cancer of the esophagus. METHODS AND MATERIALS: This retrospective study included 81 consecutive patients with resectable cancer of the esophagus who received neoadjuvant chemoradiotherapy followed by esophagectomy between January 1990 and December 1998 (inclusive). Thirty-nine patients underwent chemoradiotherapy followed by esophagectomy (CHT/RT+S), 42 received additional induction CHT followed by CHT/RT+S (CHT+CHT/RT+S). Of the 81 patients, 47 were entered in institutional or national prospective trials (6 in the CHT/RT+S and 41 in the CHT+CHT/RT+S group). Induction CHT consisted of three courses of 5-fluorouracil (5-FU), cisplatin, and paclitaxel given in 28-day cycles in 37 patients (88.1%). Concurrent CHT was 5-FU and platinum based. The median radiation dose for patients treated with CHT/RT+S was 30 Gy (range, 30-50.4 Gy) delivered in a median of 10 fractions (range, 10-28 fractions) and 45 Gy (range, 30-45 Gy) in a median of 25 fractions (range, 10-25 fractions) for patients treated with CHT+CHT/RT+S. Esophagectomy was performed 6-8 weeks after completion of concurrent chemoradiotherapy. Most patients underwent transthoracic esophagectomy (n = 66, 82.5%). RESULTS: The pretreatment characteristics were well balanced between the two groups except for age. The median follow-up time was 29 months (22 months for the CHT/RT+S group and 38.5 months for the CHT+CHT/RT+S group) for all patients and 49 months for living patients. The actuarial overall survival (OS), disease-free survival (DFS), locoregional control (LRC), and distant metastasis-free survival (DMFS) rate at 5 years for the entire group was 46%, 36.6%, 70.7%, and 53.2%, respectively. Statistically significant differences in the OS, DFS, and LRC rates between the two groups were detected. Specifically, the 5-year OS rate was 22.8% and 71.1% in the CHT/RT+S and CHT+CHT/RT+S group (p = 0.0001), respectively. The 5-year DFS rate was 27.6% and 56.6% in the CHT/RT+S and CHT+CHT/RT+S group (p = 0.003), respectively. The 5-year LRC rate was 64.2% and 85.6% in the CHT/RT+S and CHT+CHT/RT+S group (p = 0.007), respectively. The difference in the DMFS rate between the two groups was statistically significant, with a 2- and 5-year actuarial rate of 63.9% and 51.9%, respectively, in the CHT/RT+S group and 76.9% and 74.1%, respectively, in the CHT+CHT/RT+S group (p = 0.04). The statistically significant differences persisted when patients who received >/=45 Gy in each group were compared. Among those patients, the 5-year OS, DFS, LRC, and DMFS rates were 23.1%, 15.4%, 58.6%, and 39.2%, respectively, for those receiving CHT/RT+S, and 71.4% (p = 0.001), 55.8% (p = 0.0008), 84.6% (p = 0.005), and 77.3% (p = 0.009), respectively, for those receiving CHT+CHT/RT+S. The pathologic complete response (pCR) rate was greater in the CHT+CHT/RT+S group compared with in the CHT/RT+S group (p = 0.008). In univariate analysis, young age, good Karnofsky performance status, Stage II disease, total radiation dose, multiple drug regimen for concurrent CHT, pCR, R0 resection, distant disease progression, and CHT+CHT/RT+S treatment proved to be prognostic factors for OS. Lower esophageal/gastroesophageal junction tumor location, pCR, R0 resection, and CHT+CHT/RT+S treatment were favorable prognostic factors for LRC. Neither the total radiation dose nor multiple drugs for concurrent CHT were negative prognostic factors for LRC. In multivariate analysis, pCR, R0 resection, and treatment with CHT+CHT/RT+S were independent positive predictive factors for OS, and distant recurrences were negative predictive factors for OS. R0 resection, CHT+CHT/RT+S treatment, and lower esophageal/gastroesophageal junction tumor location were positive predictive factors for LRC. The radiation dose was not identified as an independent prognostic factor for either OS or LRC in the multivariate analysis. Meaningful multivariate analysis could not be performed when the multiple drug vperformed when the multiple drug variable was included in the model because of the small number of patients. CONCLUSION: Significantly greater LRC, DFS, OS, and DMFS were found in patients treated with CHT+CHT/RT+S compared with those treated with CHT/RT+S. The pCR rate was significantly higher in the CHT+CHT/RT+S group. Induction CHT was an independent favorable prognostic factor for both LRC and OS for the population included in this study. Our data suggest that a randomized trial comparing CHT+CHT/RT+S and CHT/RT+S is warranted to assess further the merits of this treatment in patients with this currently very lethal cancer.

Adult↗

PubMed2004

Preoperative induction of CPT-11 and cisplatin chemotherapy followed by chemoradiotherapy in patients with locoregional carcinoma of the esophagus or gastroesophageal junction.

BACKGROUND: Patients with localized esophageal carcinoma often develop locoregional and distant disease recurrence. The current study investigated the outcome of a new chemotherapy combination as induction therapy before chemoradiotherapy. METHODS: Forty-three patients with resectable carcinoma of the esophagus or gastroesophageal junction were enrolled. Most of the tumors were endoscopic ultrasonography (EUS) (EUS)T3 (84%) and (EUS)N1 (63%). The patients received < or = 2 6-week cycles of CPT-11 and cisplatin followed by chemoradiotherapy (45 grays with 5-fluorouracil and paclitaxel). Five to six weeks after chemoradiotherapy, the patients underwent staging and surgery. The feasibility, curative resection rates, overall and disease-free survival rates, rate of significant pathologic response, and patterns of disease recurrence were assessed. RESULTS: Of the 43 patients, 39 (91%) underwent an R0 resection. Two patients (5%) died after surgery. A pathologic complete response (pathCR) was observed in 11 (28%) of the 39 patients (or 26% of the 43 patients). In addition, 16 patients (41% of 39 patients or 37% of 43 patients) had < 10% viable tumor in the surgical specimen (pathPR). A comparison of endoscopic ultrasonograpy T and N classifications with surgical T and N classifications demonstrated significant down-staging (P < 0.01). The median survival period of all 43 patients was 22.1 months. Patients who had achieved a pathCR or pathPR had a longer median survival (25.6 months) than those who achieved less than a pathPR (18.5 months; P = 0.52). None of the clinical parameters examined were found to correlate with survival or pathologic response. CONCLUSIONS: CPT-11-based induction chemotherapy resulted in substantial pathCR and pathPR rates, both of which lead to a favorable survival outcome. The three-step strategy needs to be developed further, with the investigation of targeted therapies with chemotherapy and radiotherapy.

Adenocarcinoma↗

PubMed2004

Effects of amifostine on acute toxicity from concurrent chemotherapy and radiotherapy for inoperable non-small-cell lung cancer: report of a randomized comparative trial.

PURPOSE: To determine the ability of amifostine to reduce the severity and/or incidence of the acute toxicities of concurrent chemotherapy and radiotherapy (RT) for non-small-cell lung cancer. METHODS AND MATERIALS: Patients with inoperable, nonmetastatic non-small-cell lung cancer receiving concurrent chemoradiotherapy were randomized to one of two treatment groups. Arm 1 patients received thoracic RT (total dose, 69.6 Gy in 58 fractions of 1.2 Gy b.i.d. 5 d/wk), plus oral etoposide (50 mg b.i.d. 30 min before thoracic RT for 10 days, repeated on Day 29) and cisplatin (50 mg/m2 i.v. on Days 1, 8, 29, and 36). Arm 2 patients received the same treatment plus amifostine (500 mg i.v. 20-30 min before any treatment the first 2 days of each week). Acute effects were assessed using the National Cancer Institute Common Toxicity Criteria. RESULTS: Sixty-two patients were enrolled between November 1998 and January 2001. The minimal follow-up was 24 months, and the median follow-up of living patients was 31 months. The patient and tumor characteristics were equally distributed between the patients in the two arms. The median survival time was 20 months in Arm 1 patients and 19 months in Arm 2 patients. The maximal esophageal toxicity was mild (Grade 1) in 23%, moderate (Grade 2) in 42%, and severe (Grade 3-4) in 35% of patients in Arm 1; the corresponding rates for the Arm 2 patients were 48%, 35%, and 16% (p = 0.021). Severe pneumonitis occurred in 16% of the Arm 1 and none of the Arm 2 patients (p = 0.020, chi-square test). Neutropenic fever occurred in 39% of Arm 1 and 16% of Arm 2 patients (p = 0.046, chi-square test). Mild hypotension, dysgeusia, and sneezing were significantly more frequent among the patients in Arm 2. CONCLUSION: Amifostine reduced the severity and incidence of acute esophageal, pulmonary, and hematologic toxicity resulting from concurrent cisplatin-based chemotherapy and RT. Amifostine had no apparent effect on survival in these patients with unresectable non-small-cell lung cancer, suggesting that it does not have a tumor-protective effect.

Adult↗

PubMed2004

Feasibility of sparing lung and other thoracic structures with intensity-modulated radiotherapy for non-small-cell lung cancer.

PURPOSE: To investigate the possibility of using intensity-modulated radiotherapy (IMRT) to reduce the irradiated volumes of the normal lung and other critical structures in the treatment of non-small-cell lung cancer (NSCLC) and to investigate the effect of IMRT on the potential of spreading low doses to large volumes of normal tissues in such treatment. METHODS AND MATERIALS: A retrospective treatment planning study was performed to compare IMRT and conventional three-dimensional conformal radiation therapy (3D-CRT) for 10 NSCLC patients (Stage I-IIIB). In the IMRT plans, three to nine coplanar beams were designed to treat 95% of the planning target volume with 63 Gy and to minimize the volumes of the normal lung, esophagus, heart, and spinal cord irradiated above their tolerance doses. The two types of plans were compared with respect to the planning target volume coverage, dose-volume histograms, and other dosimetric indexes of the normal structures. RESULTS: Comparing the nine-beam IMRT plan with the 3D-CRT plan, the percentage of lung volume that received >20 Gy and the mean lung dose were reduced for all cases, with a median reduction of 8% and 2 Gy, respectively. An additional reduction of the >5-Gy volume and >10-Gy volume for the lung and thoracic tissue was more difficult with IMRT, although still possible using fewer beams in IMRT. The integral dose to the entire thorax was equivalent and even reduced for 8 of 10 cases using IMRT. CONCLUSION: It is possible to reduce the volumes of low doses (such as the >10-Gy volume and >20-Gy volume) for thoracic normal tissues using IMRT. The increased integral dose and low-dose volumes can be avoided for IMRT if such concerns are addressed carefully in the inverse planning process and with optimization of the IMRT beam configuration.

Carcinoma, Non-Small-Cell Lung↗

PubMed2004

Dose and volume reduction for normal lung using intensity-modulated radiotherapy for advanced-stage non-small-cell lung cancer.

PURPOSE: To investigate dosimetric improvements with respect to tumor-dose conformity and normal tissue sparing using intensity-modulated radiotherapy (IMRT) compared with three-dimensional conformal radiotherapy (3D-CRT) for advanced-stage non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: Forty-one patients with Stage III-IV and recurrent NSCLC who previously underwent 3D-CRT were included. IMRT plans were designed to deliver 63 Gy to 95% of the planning target volume using nine equidistant coplanar 6-MV beams. Inverse planning was performed to minimize the volumes of normal lung, heart, esophagus, and spinal cord irradiated above their tolerance doses. Dose distributions and dosimetric indexes for the tumors and critical structures in both plans were computed and compared. RESULTS: Using IMRT, the median absolute reduction in the percentage of lung volume irradiated to >10 and >20 Gy was 7% and 10%, respectively. This corresponded to a decrease of >2 Gy in the total lung mean dose and of 10% in the risk of radiation pneumonitis. The volumes of the heart and esophagus irradiated to >40-50 Gy and normal thoracic tissue volume irradiated to >10-40 Gy were reduced using the IMRT plans. A marginal increase occurred in the spinal cord maximal dose and lung volume >5 Gy in the IMRT plans, which could be have resulted from the significant increase in monitor units and thus leakage dose in IMRT. CONCLUSION: IMRT planning significantly improved target coverage and reduced the volume of normal lung irradiated above low doses. The spread of low doses to normal tissues can be controlled in IMRT with appropriately selected planning parameters. The dosimetric benefits of IMRT for advanced-stage non-small-cell lung cancer must be evaluated further in clinical trials.

Adult↗

PubMed2004

Equivalent outcome of patients with clinical Stage IIIA non-small-cell lung cancer treated with concurrent chemoradiation compared with induction chemotherapy followed by surgical resection.

PURPOSE: To compare the outcome of induction chemotherapy followed by surgery (C/S) and concurrent chemoradiotherapy (CRT) for clinical Stage IIIA non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: Between 1990 and 2000, 107 patients underwent either induction C/S (n = 55) or concurrent CRT (n = 52) for clinical Stage IIIA NSCLC at The University of Texas M. D. Anderson Cancer Center. Patient and tumor characteristics were balanced in the two treatment groups with respect to T and N stage, race, median age, performance status, weight loss, and histologic findings. In the C/S group, induction chemotherapy included two to four cycles of cisplatin-based chemotherapy followed by lobectomy and mediastinal lymph node dissection. Postoperative RT was delivered in 35 patients, with referral for RT made at the discretion of the treating physician. CRT consisted of three cycles of cisplatin-based chemotherapy given every 3 weeks concurrent with RT to 60-63 Gy in 30-35 fractions in 27 patients and 69.6 Gy in 58 fractions (b.i.d.) in 25 patients. Local control, overall disease-free survival, and distant metastasis-free survival rates were calculated using the Kaplan-Meier method. The median follow-up duration was 20 months in all patients and 32 months in surviving patients. RESULTS: No statistically significant differences were found in the end points measured in the two treatment groups. Specifically, the median survival time was 31 and 27 months and the 5-year overall survival rate was 33% and 30% in the C/S and CRT groups, respectively. Likewise, the 5-year local control (58% vs. 61%), disease-free (24% vs. 23%), and distant metastasis-free (44% vs. 36%) survival rates in the two groups were not significantly different. In the C/S group, postoperative RT significantly improved the 5-year local control rate from 33.8% to 81.5% (p = 0.007) but did not significantly improve overall survival. Additionally, patients in the C/S group whose disease responded to induction chemotherapy had a significantly improved 5-year overall survival rate (50%) compared with those who had stable or progressive disease (16%, p = 0001). CONCLUSION: Treatment of Stage IIIA NSCLC using either induction C/S or CRT resulted in similar outcomes in terms of local control and median overall, 5-year overall, distant metastasis-free, and disease-free survival. However, patients undergoing induction C/S often needed postoperative RT to achieve local control equivalent to that achieved with concurrent CRT. Advances in radiation-based treatment as reflected in this study have resulted in similar outcomes compared with modern induction C/S. To improve survival, however, newer systemic agents that reduce and control distant metastasis are required.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2004

Dosimetric benefits of respiratory gating: a preliminary study.

In this study, we compared the amount of lung tissue irradiated when respiratory gating was imposed during expiration with the amount of lung tissue irradiated when gating was imposed during inspiration. Our hypothesis was that the amount of lung tissue spared increased as inspiration increased. Computed tomography (CT) image data sets were acquired for 10 patients who had been diagnosed with primary bronchogenic carcinoma. Data sets were acquired during free breathing and during breath-holds at 0% tidal volume and 100% tidal volume, and, when possible, at deep inspiration, corresponding to approximately 60% vital capacity. Two treatment plans were developed on the basis of each of the gated data sets: one in which the treatment portals were those of the free-breathing plan, and the other in which the treatment portals were based on the gated planning target volumes. Dose-mass histograms of the lungs calculated at 0% tidal volume were compared to those calculated at deep inspiration and at 100% tidal volume. Data extracted from the dose-mass histograms were used to determine the most dosimetrically beneficial point to gate, the reduction in the amount of irradiated lung tissue that resulted from gating, and any disease characteristics that might predict a greater need for gating. The data showed a reduction in the mass of normal tissue irradiated when treatment portals based on the gated planning target volume were used. More normal lung tissue was spared at deep inspiration than at the other two gating points for all patients, but normal lung tissue was spared at every point in the respiratory cycle. No significant differences in the amount of irradiated tissue by disease characteristic were identified. Respiratory gating of thoracic radiation treatments can often improve the quality of the treatment plan, but it may not be possible to determine which patients may benefit from gating prior to performing the actual treatment planning.

Artifacts↗

PubMed2004

Utility of PET, CT, and EUS to identify pathologic responders in esophageal cancer.

BACKGROUND: This study evaluates the utility of positron emission tomography (PET), endoscopic ultrasonography (EUS), and computed tomographic (CT) scans to predict pathologic response and survival following preoperative chemoradiation (CRT) in esophageal cancer. METHODS: One hundred three sequential patients with locoregionally advanced esophageal cancer, who were treated with CRT and esophageal resection between May 2001 and November 2003 at the University of Texas M.D. Anderson Cancer Center, were retrospectively reviewed. PET, EUS, and CT were performed before (pre) or after (post) CRT and before surgical resection. PET standardized uptake value (SUV) was defined as maximal uptake in primary tumor. RESULTS: Most patients were male (91 [88%]) with adenocarcinoma (90 [87%]). Pretreatment clinical stages were: IIA (42 [41%]), IIB (5 [5%]), III (50 [49%]), and IVA (6 [6%]). At the time of surgery, 58 patients (56%) had a pathologic response to CRT (< or =10% viable cells). Post-CRT measurements that correlated with pathologic response were: CT esophageal wall thickness (13.3 vs 15.3 mm, p = 0.04), EUS mass size (0.7 vs 1.7 cm, p = 0.01) and PET SUV (3.1 vs 5.8, p = 0.01). Post-CRT PET SUV equal to or greater than 4 had the highest accuracy for pathologic response (76%). Univariate and multivariate Cox regression analysis demonstrated that a post-CRT PET SUV equal to or greater than 4 was an independent predictor of survival (HR, 3.5, p = 0.04). CONCLUSIONS: The FDG-PET SUV is the most accurate noninvasive test to predict long-term survival after preoperative CRT and before surgical resection. Post-CRT FDG-PET cannot, however, rule out residual microscopic disease so esophagectomy should remain a therapeutic option even if the post-CRT imaging modalities are normal.

Adenocarcinoma↗

PubMed2004

Prolonged survival in patients with resected non-small cell lung cancer and single-level N2 disease.

OBJECTIVES: To test the hypothesis that patients with non-small cell lung cancer and single-level N2 metastases constitute a favorable subgroup of patients with mediastinal metastases, we analyzed the results of the Eastern Cooperative Oncology Group 3590 (a randomized prospective trial of adjuvant therapy in patients with resected stages II and IIIa non-small cell lung cancer) by site of primary tumor and pattern of lymph node metastases. METHODS: Accurate staging was ensured by mandating either systematic sampling or complete dissection of the ipsilateral mediastinal lymph nodes. The overall survival of patients with left lung non-small cell lung cancer and metastases in only 1 of lymph node levels 5, 6, or 7 and right lung non-small cell lung cancer with metastases in only 1 of levels 4 or 7 was compared with that of patients with N1 disease originating in the same lobe. RESULTS: The median survival of the 172 patients with single-level N2 disease was 35 months (95% confidence interval: 27-40 months) versus 65 months (95% confidence interval: 45-84 months) for the 150 patients with N1 disease (median follow-up 84 months, P =.01). However, among patients with left upper lobe tumors, survival was not significantly different between patients with N1 disease and patients with single-level N2 disease (49 vs 51 months, P =.63). The median survival of the 71 patients with single-level N2 metastases without concomitant N1 disease (skip metastases) was 59 months (95% confidence interval: 36-107 months) versus 26 months (95% confidence interval: 16-36 months) for the 145 patients with both N1 and N2 metastases (P =.001). CONCLUSIONS: Survival of patients with left upper lobe non-small cell lung cancer and metastases to single-level N2 lymph nodes is not significantly different from that of patients with N1 disease. The presence of isolate N2 skip metastases is associated with improved survival when compared with patients with both N1 and N2 disease. Survival should be reported by the lobe of primary tumor and metastatic pattern to guide future clinical trial development, treatment strategies, and revisions of the TNM staging system.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2004

Phase II study of a multidisciplinary approach with induction chemotherapy, followed by surgical resection, radiation therapy, and consolidation chemotherapy for unresectable malignant thymomas: final report.

PURPOSE: To evaluate tumor resectability after induction chemotherapy and to determine disease-free and overall survival rates of patients with locally advanced unresectable thymoma that received a multimodal treatment regimen. PATIENTS AND METHODS: Twenty-two patients (9 men, 13 women) with histologically confirmed invasive thymoma were treated with a multidisciplinary regimen consisting of three courses of induction chemotherapy, surgical resection, and radiation therapy, followed by three courses of consolidation chemotherapy. The median age was 47 years (range, 25-70). Eleven patients had stage III disease, 10 patients, stage IVA, and one patient, IVB. The most common histologic type was lymphocytic. Induction chemotherapy consisted of 500 mg/m(2) of cyclophosphamide on day 1; doxorubicin (20 mg/m(2) per day) on days 1-3 via continuous infusion (a total of 60 mg/m(2)); cisplatin (30 mg/m(2) per day) on days 1-3 (a total of 90 mg/m(2)); and prednisone (100 mg per day) on days 1-5. This cycle was repeated three times at 3-4-week intervals. Patients then underwent surgery for tumor resection and received radiotherapy. Consolidation chemotherapy given at 80% of the induction chemotherapy doses of cyclophosphamide, doxorubicin, and cisplatin and 100% of the dose of prednisone was then repeated every 3-4 weeks for a total of three courses. RESULTS: Induction chemotherapy produced major responses in 17 (77%) of the 22 patients including 3 (14%) complete responses (CR) and 14 (63%) partial responses (PR). Twenty-one patients underwent surgical exploration: 16 (76%) had complete resection and 5 (24%) had incomplete resection; one patient refused surgery. All 22 patients received radiation therapy. Nineteen of 22 patients completed the planned therapy, and all but one had completed consolidation chemotherapy at the time of analysis. With a median follow-up time of 50.3 months, 18 of the 19 patients who completed the multidisciplinary approach were disease-free. Of the 22 patients originally registered, 20 were alive at the time of analysis (one patient died of endocarditis, and one died of recurrent disease). The overall survival rate was 95% at 5 years (95% confidence interval (CI), 0.87-1.0) and 79% at 7 years (95% CI, 0.55-1.0). The progression-free survival rates were 77% at 5 years (95% CI, 0.58-1.0) and 77% at 7 years (95% CI, 0.58-1.0). The major side effect from induction and consolidation chemotherapy was myelosuppression. Nine patients experienced grade III/IV neutropenia, which included neutropenic fever in two patients, and grade III thrombocytopenia in two patients. The most common nonhematologic side effects were fatigue, nausea and vomiting, and decreased appetite. One patient experienced acute respiratory distress syndrome after surgical resection and required a prolonged hospitalization. No patients developed cardiac toxic effects, and no surgical mortality occurred. CONCLUSIONS: The use of induction chemotherapy to optimize surgical resectability of thymoma followed by radiation therapy and consolidation chemotherapy lead to good control of residual disease and high overall survival rates. We believe that this combined multidisciplinary approach prolongs lives and may cure locally advanced unresectable malignant thymomas. Future prospective multi-institutional studies are needed to further verify or define the best treatment for this patient population.

Adult↗