Correlation of molecular response as measured by 18-FDG positron emission tomography with outcome after chemoradiotherapy in patients with esophageal carcinoma.

PURPOSE: To determine whether 18-fluorodeoxyglucose positron emission tomography (PET) computed tomography scans predict the pathologic complete response and disease-free and overall survival in patients with esophageal carcinoma undergoing definitive or preoperative chemoradiotherapy. METHODS AND MATERIALS: The records of patients with esophageal carcinoma presenting for definitive or preoperative treatment and undergoing pre- and post-treatment 18-fluorodeoxyglucose PET-computed tomography scans were retrospectively reviewed. The histologic type, T stage, and nodal status were the variables investigated to determine a relationship with the baseline standardized uptake value (SUV) of the primary tumor at diagnosis. We also attempted to determine whether a relationship exists between the percent decrease in SUV and a pathologic complete response, overall and disease-free survival. RESULTS: A total of 81 patients, 14 women and 67 men, underwent 18-fluorodeoxyglucose PET-computed tomography scanning before treatment and 63 also had post-treatment scans. T stage and tumor location predicted in univariate, but not multivariate, analysis for the initial SUV. Of the patients with a postchemoradiotherapy SUV of <2.5, 66% had tumor in the surgical specimen and 64% of patients had positive lymph nodes at surgery that were not imaged on the postchemoradiotherapy PET scan. A trend existed for post-treatment SUV and the days from radiotherapy to surgery to predict for a pathologic complete response (p = 0.09 and p = 0.08, respectively). The post-treatment SUV predicted for disease-free survival in the definitive chemoradiotherapy group (p = 0.01). CONCLUSIONS: A correlation was found between the depth of tumor invasion and the baseline SUV. The post-treatment SUV predicted for disease-free survival in the definitive chemoradiotherapy group. Caution should be exercised in using post-treatment PET scans to determine the necessity for surgical resection.

A phase II study of concurrent carboplatin and paclitaxel and thoracic radiotherapy for completely resected stage II and IIIA non-small cell lung cancer.

BACKGROUND: To determine the feasibility of combining concurrent carboplatin/paclitaxel and thoracic radiotherapy (TRT) for completely resected stage II and IIIA non-small cell lung cancer. METHODS: Eligibility stipulated gross total resections with involved lymph nodes (N1 or N2), pathologic stage II or IIIA non-small cell lung cancer. TRT consisted of 50.4 Gy in 28 fractions with a boost of 10.8 Gy for extranodal extension (ENE) or 16.2 Gy for involved surgical margins. Chemotherapy was administered every 3 weeks: carboplatin (area under the curve of 5) and paclitaxel (175 mg/m2) during TRT for two cycles, with doses increased to an area under the curve of 7.5 and 225 mg/m2, respectively, for two cycles after TRT. Cox multivariate regression analysis was used to confirm independent predictors of outcome among clinical and treatment-related factors: age, T stage, N stage, presence of ENE, presence of involved surgical margins, histopathology. RESULTS: Between April 1997 and March 2001, 42 patients were enrolled. Two patients were deemed ineligible due to having T4 disease, leaving 40 patients for analysis. Ninety-two percent (37/40) of patients had T1 or T2 disease; 60% (24/40) had N2 disease. Nine patients (22.5%) had ENE and 15% (six patients) had involved surgical margins. At a median follow up of 37 months (range, 3-103; median, 68 months for living patients), the 2- and 5-year Kaplan-Meier estimates of local regional control, freedom from distant metastasis, freedom from brain metastasis, and overall survival were 92% and 88%, 77% and 59%, 87% and 71% and 72% and 44%, respectively. Fourteen patients developed distant metastasis as the initial site of failure, eight of whom had brain metastasis. Brain metastasis was the only site of failure in four of the eight patients. Multivariate regression analysis demonstrated that the only independent predictor of overall survival was histology (p = 0.02). Patients with adenocarcinoma had a 5-year overall survival of 28% versus 68% for all other cell types. There were no independent predictors of distant metastases or brain metastases on multivariate regression analysis. Treatment was tolerated reasonably well: 92% of patients (37/40) received the planned doses of TRT; 67% of patients (27/40) received all four cycles of chemotherapy. Five patients developed grade 3 esophagitis, and three patients experienced grade 3 pneumonitis. Two patients experienced grade 5 toxicity. One was treatment related due to a patient who developed grade 3 esophagitis who developed an aspiration pneumonia that progressed to acute respiratory distress syndrome. CONCLUSIONS: Our results support the Radiation Therapy Oncology Group 97-05 findings and suggest that with new and better tolerated chemotherapy regimens the strategy of concurrent TRT and chemotherapy after completely resected stage II and IIIA non-small cell lung cancer should be further explored.

Radiofrequency ablation of lung malignancies.

Radiofrequency ablation is a new technology that has been used successfully to treat hepatic tumors. Recently, an increasing number of reports have described the use of radiofrequency ablation for primary and metastatic lung tumors. Although such early experience appears promising, many questions regarding patient selection, radiofrequency ablation technique, effectiveness of ablation on lung tumors, radiographic follow-up, and survival remain unanswered. This article addresses these issues and provides the thoracic surgeon with a current review of the application of radiofrequency ablation to lung tumors.

Induction cisplatin and paclitaxel followed by combination chemoradiotherapy with 5-fluorouracil, cisplatin, and paclitaxel before resection in localized esophageal cancer: a phase II report.

BACKGROUND: Multimodality therapy for esophageal cancer holds promise for improving outcome in this lethal disease. On the basis of encouraging data from a phase I trial, we conducted a phase II study of preoperative chemotherapy, followed by concurrent chemoradiotherapy and surgery. METHODS: Patients with clinically staged resectable esophageal cancer were treated with induction cisplatin and paclitaxel, followed by 45 Gy of external beam radiation with concurrent infusional 5-fluorouracil and weekly cisplatin and paclitaxel. Four to eight weeks after multimodality induction, esophagectomy was performed in suitable patients. Study end points were survival, pathologic complete response, and toxicity. RESULTS: Twenty-one patients were enrolled with a median age of 58 years, and all patients were clinically staged II or III. Sixteen (76.2%) patients completed the trial, of whom four (25%) had a pathologic complete response. One patient died from postoperative complications. Grade 3 or 4 toxicity was observed in 76% of patients, and dose-limiting toxicity was seen in 6 of the first 14 patients, thus necessitating a planned dose reduction of paclitaxel. At a median follow-up of 30 months, 13 patients remain alive. The 2-year disease-specific survival for the study population was 78%. CONCLUSIONS: This regimen of multimodality therapy before resection resulted in an encouraging 2-year survival rate but a disappointing rate of pathologic complete response and was toxic, necessitating a predetermined paclitaxel dose reduction. The incorporation of taxanes into induction strategies for esophageal cancer seems promising, but the optimal schedule remains undefined.

Surgical patterns of care in operable lung carcinoma treated with radiation.

PURPOSE: To determine the national surgical practice patterns of care for operable lung cancer patients treated with radiation. MATERIALS AND METHODS: A nationwide survey of a stratified random sample of institutions was conducted for patients who had non-metastatic lung cancer, Karnofsky Performance Scores (KPS) > or =60, and who had received radiation therapy as definitive or adjuvant treatment. Among 541 patients, representing a weighted sample size of 42,335 patients nationwide, 131 (19.8%) underwent surgery as part of their therapy. Pearson chi statistics were used to analyze characteristics of this subset of patients. RESULTS: Of the 131 patients who underwent surgery, 126 patients who had non-small cell lung cancer (NSCLC) were analyzed. Surgical patients were younger, had less weight loss, higher KPS, and higher forced expiratory volume within 1 second (FEV1) values than those treated without surgery. Surgical patients had more stage I/II (53.5% vs 32.2%; p = 0.0004) and less clinical N2/N3 disease (28.8% vs 47.5%; p = 0.002) than nonsurgical patients. Surgery consisted of lobectomy or bilobectomy in 63.2% of patients, pneumonectomy in 23.5%, and wedge resection in 5.9%. Of the patients, 80.4% received radiation in the adjuvant setting and 9.9% in the neoadjuvant setting. CONCLUSIONS: Patients with non-metastatic lung cancer who are treated surgically and with radiation have clinically less advanced disease than those treated with radiation alone. Most radiation therapy in this setting is administrated postoperatively and secondary to hilar and/or mediastinal nodal involvement undetected before surgery. Improved preoperative nodal staging and neoadjuvant approaches may alter these practice patterns.

Radiofrequency ablation of primary lung cancer: results from an ablate and resect pilot study.

STUDY OBJECTIVES: The role of radiofrequency ablation (RFA) for primary lung cancer remains poorly defined. The purpose of this "ablate and resect" pilot study was to evaluate the safety of performing RFA in patients with primary non-small cell lung cancer (NSCLC) and to characterize the histologic changes in tumor tissue following such ablation. DESIGN: This prospective study was undertaken at a single institution, and 10 patients were accrued from June 2002 to June 2003. Eligible patients included those with clinical stage I or II disease. RFA of the tumor was performed through a standard thoracotomy followed by conventional lobectomy and lymph node dissection. Extent of cell death was determined histologically. MEASUREMENTS AND RESULTS: Following the exclusion of two patients, the treated portions of eight tumors were examined for tumor cell viability. Gross inspection and routine histologic staining could not reliably identify the "immediately ablated" tissue. However, using a supravital staining technique, the treated areas from seven of the eight tumors (87.5%) demonstrated > 80% nonviability (100% nonviability was noted in the treated areas from three of the eight tumors). No bleeding or thermal complications were noted at the time of RFA, and none of the patients had skin burns at the electrode dispersive pad sites. CONCLUSIONS: RFA of primary NSCLC is feasible and can be performed safely in the setting of an open thoracotomy. Complete tumor cell necrosis, as determined by supravital staining, was noted in the treated areas from three of eight tumors (37.5%). Such complete ablation was observed in the treated areas from smaller tumors (< 2 cm), whereas the treated areas from larger tumors demonstrated incomplete ablation. Additional investigation with histopathologic correlation is needed to fully assess the long-term efficacy of RFA for NSCLC.

A randomized pilot study of cognitive-behavioral therapy versus basic health education for smoking cessation among cancer patients.

BACKGROUND: Previously, we have linked theoretically based cognitive and emotional variables to the ability of cancer patients to quit smoking. PURPOSE: In this study, we evaluated the impact of cognitive-behavioral therapy (CBT), which addressed these theoretically derived cognitive and emotional variables linked to tobacco use in this population, for promoting smoking cessation in a sample of cancer patients and assessed longitudinal predictors of smoking cessation. METHODS: Cancer patients (N=109) were randomized to either the theoretically based CBT intervention or to a general health education (GHE) condition, and all patients received nicotine replacement therapy. RESULTS: Contrary to our expectation, no significant difference in 30-day point-prevalence abstinence between the CBT and GHE conditions was detected at either a 1-month (44.9 vs. 47.3%, respectively) or 3-month (43.2% vs. 39.2%, respectively) follow-up evaluation. Higher quit motivation and lower cons of quitting were related to smoking cessation. CONCLUSIONS: Implications for the implementation of smoking cessation behavioral treatments in the oncologic context are discussed, as are directions for future research in this area.

The surgical management of superior sulcus tumors: a retrospective review with long-term follow-up.

BACKGROUND: We reviewed our experience with multimodality therapy for superior sulcus tumors to identify aspects of treatment that impact survival. METHODS: We retrospectively analyzed the records of 39 consecutive patients who underwent surgical resection in a single institution between 1993 and 2000. RESULTS: Median age at presentation was 59 years (range, 40 to 77). Twenty-five patients (64%) were men. At presentation, 36 patients (92%) had clinical T3 tumors and 3 (8%) had clinical T4 tumors. Mediastinoscopy was negative in all patients. Thirty-one patients (79%) received preoperative radiotherapy (median dose, 4500 cGy). Chemotherapy was administered concurrently with radiotherapy in 27 patients (69%). Complete surgical resection was performed in 34 patients (87%). There were 2 (5%) postoperative deaths. Of the 31 patients who received preoperative therapy, 14 (45%) had their tumors downstaged and 9 (29%) demonstrated a complete pathologic response. Median follow-up (100%) was 69 months. Overall 5-year survival was 47.9%. Five-year survival was 52.1% in patients with negative resection margins (p = 0.005), and 60.6% in patients who demonstrated a response to induction chemoradiation therapy (p = 0.008). Independently, margin status and response to induction therapy are predictors of overall survival (p = 0.01 and p = 0.02, respectively). Multivariable analysis identified margin status as the only factor significantly associated with overall survival. Negative margins strongly correlated with the response to preoperative therapy (p = 0.004). Disease-free survival correlated well with the response to induction therapy (p = 0.03). The chemotherapy regimen, T status, operative procedure, and complete pathologic response did not correlate with survival. CONCLUSIONS: The use of chemoradiation induction therapy may downstage tumors, enhance the ability to obtain a complete surgical resection, and prolong survival.

Complete response to neoadjuvant chemoradiotherapy in esophageal carcinoma is associated with significantly improved survival.

PURPOSE: Attempts to improve survival of patients with esophageal cancer have been made using induction chemoradiotherapy (CRT) followed by surgery. A large single-center experience was reviewed to determine which treatment-related variables could predict survival and recurrence. PATIENTS AND METHODS: All patients undergoing esophagectomy between January 1994 and December 2002 were reviewed. Univariate and multivariate analyses were performed using log-rank and Cox proportional hazards models, and survival curves were estimated using the Kaplan-Meier method. RESULTS: Of 171 patients with invasive cancer, 131 (77%) underwent preoperative CRT. The average age was 60 years, and most patients were male (85%). Operations performed included Ivor-Lewis (60%), transhiatal (8%), three-hole (23%), or left thoracoabdominal (8%) esophagectomy. Perioperative mortality rate was 5%. Median overall survival (OS) of the entire group was 33 months, and the 5-year OS rate was 26%. Induction CRT was associated with a 33% 5-year survival rate compared with 11% for surgery alone (P = .43). Patients downstaged to pathologic stage 0 or I had an improved OS and disease-free survival (DFS) compared with those patients who were not downstaged (P = .022). Additionally, the ability to perform an R0 resection was a significant factor for OS and DFS (n = 130; P < .0001 and P <.0002, respectively). CONCLUSION: Response to CRT and the ability to perform an R0 resection are associated with significantly improved survival in patients with esophageal carcinoma.

Morbidity and mortality are not increased after induction chemoradiotherapy followed by esophagectomy in patients with esophageal cancer.

Attempts to improve survival of patients with esophageal cancer have been made using induction chemoradiotherapy (CRT) followed by surgery. This approach may be associated with higher complication rates. A large single-center experience was reviewed to determine whether induction CRT was associated with increased morbidity and mortality among 179 patients undergoing esophagectomy between January 1994 and December 2002. Morbidity was recorded as any complication requiring additional intervention. Mortality was defined as patient death within the first 30 postoperative days or death during the initial hospitalization. In total, 131 patients underwent induction CRT followed by surgery. The most common operation was an Ivor-Lewis esophagogastrectomy (60%). Median survival of the entire group was 33 months and 5-year survival was 26%. Perioperative mortality was 5% and did not differ between induction (4.6%) and non-induction (6.3%) groups. The overall complication rate was 57%, reflecting a very liberal definition of postoperative complications. There were no differences between the two groups in terms of such major complications as anastomotic leak, pneumonia, acute respiratory distress syndrome, respiratory failure, chylothorax, atrial arrhythmia, and wound infections. There were only two complications that occurred more frequently in the induction group--venous thrombosis (8.4% v 0%) and vocal cord paresis (7.6% v 2.1%). The median hospital stay was similar in patients who had complications versus those who did not (12 v 13 days) and in patients who underwent induction CRT versus those that did not (12 days v 13.5 days). Esophagectomy can be performed safely with low mortality and acceptable morbidity following neoadjuvant chemotherapy and radiation with no increase in hospital stay for patients with complications.

Surgical palliation of thoracic malignancies.

Primary and metastatic thoracic malignancies are often incurable. Surgeons caring for these patients must be familiar with the options,indications, techniques, and limitations of interventions for palliative treatments in these patients. This article is an overview of the current practices for palliation of a broad spectrum of complaints relating to patients with carcinomas of the lung, esophagus,and mesothelium. The information can be used for treatment of patients with complaints secondary to less common malignancies and metastatic disease of the thorax.

Characteristics of cancer patients entering a smoking cessation program and correlates of quit motivation: implications for the development of tobacco control programs for cancer patients.

Even though survival and quality of life are adversely affected by smoking among cancer patients, about one-third of cancer patients who smoked prior to their diagnosis continue to smoke. One barrier to the provision of smoking cessation treatments to cancer patients is the paucity of data on the characteristics of cancer patients who continue to smoke and a lack of data on correlates of quit motivation in this population. This descriptive study assessed demographic, medical, smoking history, and psychological characteristics of cancer patients in a smoking cessation program (N=111) and examined these characteristics as correlates of quit motivation. Methods used by patients to quit smoking were also queried. We found that: (1) most patients are Caucasian, married, diagnosed with head and neck (versus lung) cancer, highly addicted to nicotine, and in the contemplation or preparation stage of change; (2) most patients attempt to quit smoking without formal treatment, although 33-50% have used the transdermal nicotine patch, nicotine gum, or bupropion; (3) depressive symptoms, low quitting self-efficacy, low perceived risk, and low perceived benefits of quitting are prevalent among patients, but most patients do not endorse the perceived disadvantages of quitting or fatalistic beliefs; and (4) quit motivation is associated with higher quitting self-efficacy, risk perceptions, and perceived benefits of quitting, lower tobacco use and nicotine addiction, and shorter time since diagnosis. These findings can help guide the development of smoking cessation interventions for cancer patients.

Comparing cancer patients who enroll in a smoking cessation program at a comprehensive cancer center with those who decline enrollment.

BACKGROUND: Despite the availability of smoking interventions for cancer patients, many eligible patients decline enrollment into such programs. We examined reasons patients provide for declining smoking treatment and compared treatment decliners to enrollees. METHODS: Eligible cancer patients (N = 231) were offered smoking cessation treatment. During recruitment, demographic, medical (eg, cancer stage), and smoking-related behavioral (eg, readiness to quit) data were collected, and decliners stated a reason for refusal. Patients who enrolled in the cessation program (N = 109) were compared with those who declined (N = 122) in terms of recruitment data, and reasons for declining were compiled. RESULTS: Decliners were significantly more likely to: (1) have head and neck cancer (vs lung cancer); (2) exhibit fewer physical symptoms (eg, shortness of breath); (3) report a lower readiness to quit smoking; (4) indicate no intention to quit smoking; and (5) smoke fewer cigarettes. A preference to quit without professional assistance was the most common reason for declining treatment. CONCLUSIONS: Our findings highlight important differences between patients who enroll in a smoking cessation program and those who decline and underscore the need for motivational interventions to facilitate enrollment into smoking interventions for cancer patients.

Survival following intensive preoperative combined modality therapy with paclitaxel, cisplatin, 5-fluorouracil, and radiation in resectable esophageal carcinoma: a phase I report.

PURPOSE: To assess the benefits of aggressive chemoradiation therapy followed by surgery in resectable esophageal carcinoma. METHOD: Twenty-nine patients with resectable carcinoma were treated with 60 Gy of radiation (2 Gy daily for 6 weeks) and concurrent chemotherapy consisting of continuous infusion of 5-fluorouracil (200-225 mg/m(2)/d), paclitaxel (25, 40, 50, or 60 mg/m(2)) weekly over 1 hour, and cisplatin (25 mg/m(2)) weekly immediately following paclitaxel throughout radiation. Patients received either 4 cycles of postoperative paclitaxel 175 mg/m(2) over 3 hours and cisplatin 75 mg/m(2) every 3 weeks or paclitaxel 175 mg/m(2) over 3 hours and cisplatin 75 mg/m(2) every 3 weeks prior to the initiation of chemoradiation. After induction therapy and restaging, esophagectomy was performed 4 to 6 weeks later. RESULTS: Twenty-seven patients were eligible for study (26 men, 23 with adenocarcinoma). Median age was 58 years (range 30-73). The maximum tolerated dose combination was paclitaxel 50 mg/m(2) over 1 hour weekly, cisplatin 25 mg/m(2) over 1 hour weekly, 5-fluorouracil 200 mg/m(2)/d by continuous infusion throughout radiotherapy and radiation to 60 Gy. Twenty-two patients completed therapy and underwent surgical resection. Four patients had complete pathological responses and 18 had partial responses with no mortality. The commonest dose-limiting toxicity was mucositis and esophagitis (n = 7). Median follow-up of 27 patients was 150 weeks (range 7-303). At 2-year follow-up 16/27 (59%) were alive and 15/27 (56%) were free of disease. At 4-year follow-up 12/27 (44%) were alive and free of disease. Median follow-up of 22 patients undergoing esophagectomy was 205 weeks (range 26-303). At 4-year follow-up 10/22 (45%) were alive and free of disease. For the 18 patients treated at or above the maximum tolerated dose, median follow-up was 151 weeks (range 35-206) and at 3-year follow-up 9/18 (50%) were alive and free of disease. CONCLUSION: Aggressive combined modality therapy of esophageal carcinoma was associated with excellent long-term survival in this phase I trial.

Longitudinal predictors of continued tobacco use among patients diagnosed with cancer.

Even though continued smoking by cancer patients adversely affects survival and quality of life, about one third of patients who smoked prior to their diagnosis continue to smoke after their diagnosis. The implementation of smoking cessation treatments for cancer patients has been slowed by the lack of data on correlates of tobacco use in this population. Thus, this longitudinal study assessed demographic, medical, addiction, and psychological predictors of tobacco use among 74 head, neck, and lung cancer patients. Multivariable binary logistic regression analyses, with outcome categorized as smoker or nonsmoker, indicated that the likelihood that patients would be a smoker was associated with lower levels of perceived risk and a higher level of quitting cons. Multivariable nominal logistic regression, with outcome classified as continuous smoker, continuous quitter, relapser, or follow-up quitter, indicated that: (a). patients categorized as continuous smokers reported significantly lower quitting self-efficacy than follow-up quitters and continuous quitters, (b). relapsers reported a significantly lower level of quitting self-efficacy than either follow-up quitters or continuous quitters, and (c). continuous smokers exhibited a significantly lower level of risk perceptions than continuous abstainers. These findings can be useful for the development and evaluation of treatments to promote smoking cessation among cancer patients.

Quality of life after esophagectomy for cancer.

PURPOSE/OBJECTIVES: To examine symptoms and quality of life (QOL) of esophagectomy patients after curative surgery. DESIGN: Longitudinal, descriptive pilot study. SETTING: Comprehensive cancer center in the northeastern United States. SAMPLE: 23 patients were surveyed: 20 men and 3 women. The mean age was 62.3 years. METHODS: The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (version 2.0) and the esophageal-specific module were used. Data collection included three or four time points: before neoadjuvant treatment (if administered), before surgery, and three and six months after surgery. MAIN RESEARCH VARIABLES: The effects on symptoms and QOL of curative esophagectomy performed by a thoracic surgical oncologist. FINDINGS: Global QOL declined slightly over time; this change was not statistically significant. A significant inverse relationship was found between symptom intensity and global QOL. The intensity of hoarseness, reflux, and diarrhea increased significantly pre- to postsurgery. The average symptom intensity for the esophageal-specific subset of 24 symptoms increased significantly over time; the greatest intensity was found before surgery. CONCLUSIONS: Over the six-month observation period, the study found little average change in global QOL or functional status. However, symptoms increased significantly during this time period. Increased symptoms were associated with decreased QOL. IMPLICATIONS FOR NURSING: Symptom management should focus on symptoms that interfere with patients' QOL. Further research should target the evaluation of specific interventions for symptoms.

Multimodality therapy for resectable cancer of the thoracic esophagus.

The frequency of esophageal carcinoma continues to increase in North America primarily because of the increased incidence of Barrett's epithelium in the distal esophagus and its malignant potential. Aggressive treatments involving multimodality therapies have been offered to improve overall poor survival rates. A review of this experience follows, to explain the rationale and to compare results of therapies. Although preoperative chemoradiation therapy is commonly used for locally advanced disease, few data support its superiority over surgical resection alone, followed by adjuvant therapy when appropriate. Hence this regimen should be limited to patients enrolled in controlled, randomized studies until the data support its widespread use.