A pilot study of stereotactic body radiation therapy (SBRT) after surgery for stage III non-small cell lung cancer.

BACKGROUND: Standard therapy for stage III non-small cell lung cancer with chemotherapy and conventional radiation has suboptimal outcomes. We hypothesized that a combination of surgery followed by stereotactic body radiation therapy (SBRT) would be a safe alternative. METHODS: Patients with stage IIIA (multistation N2) or IIIB non-small cell lung cancer were enrolled from March 2013 to December 2015. The protocol included transcervical extended mediastinal lymphadenectomy (TEMLA) followed by surgical resection, 10 Gy SBRT directed to the involved mediastinum/hilar stations and/or positive surgical margins, and adjuvant systemic therapy. Patients not suitable for anatomic lung resection were treated with 30 Gy to the primary tumor. The primary efficacy end-point was the proportion of patients with grade 3 or higher adverse events (AE) or toxicities. RESULTS: Of 10 patients, 7 patients underwent neoadjuvant chemotherapy. All patients had TEMLA. Nine of 10 patients underwent surgical resection. The remaining patient had an unresectable tumor and received 30 Gy SBRT to the primary lesion. All patients had post-operative SBRT. Median follow-up was 18 months. There were no perioperative mortalities. Six patients had any grade 3 AEs with no grade 4-5 AEs. Of these, 4 were not attributable to radiation. Pulmonary-related grade 3 AEs were experienced by 2 patients. There were no failures within the 10 Gy volume. Overall survival and progression-free survival rates at 2 years were 68% (90% CI 36-86) and 40% (90% CI 16-63), respectively. CONCLUSIONS: In carefully selected patients with locally advanced non-small cell lung cancer, combining surgery with SBRT was well tolerated with no local failure. TRIAL REGISTRATION: ClinicalTrials.gov identifying number NCT01781741 . Registered February 1, 2013.

Outcomes of endoscopic resection for high-grade dysplasia and esophageal cancer.

BACKGROUND: Endoscopic resection (ER) is an important advance in the management of esophageal tumors. It has been used successfully for superficial esophageal cancer and high-grade dysplasia (HGD) arising out of Barrett epithelium. METHODS: From a single institution within the Department of Surgery, patients who underwent ER for esophageal tumors between December 2001 and January 2012 were evaluated. Demographic, clinical, and pathologic variables were collected and reviewed. RESULTS: We identified 81 patients who underwent ER for esophageal lesions. Median patient age was 69 years, and the median follow-up was 3.25 years. In patients with HGD, at the time of last endoscopy, the complete eradication rate of HGD was 84 % and cancer-specific survival was 100 %. During surveillance, one patient developed an invasive carcinoma that required endoscopic therapy. Patients with T1a and negative deep margins on ER had a recurrence-free and cancer-specific survival of 100 %. There were seven patients with T1b and negative margins on ER. Three patients underwent esophagectomy; final pathology revealed no residual malignancy or lymph node metastasis. Two patients had definitive chemoradiation, and two patients were observed. To date, there has been no cancer recurrence. In all patients who underwent ER, there was one episode of bleeding that required endoscopic treatment and admission for observation. CONCLUSIONS: ER can be performed safely and can adequately stage and often treat patients with HGD and superficial cancers. Patients with HGD and T1a disease with negative margins are cured with ER alone. Observation and surveillance may be an option for select patients with low-risk, early submucosal disease (T1b) and negative margins.

Capecitabine, oxaliplatin and radiotherapy: a phase IB neoadjuvant study for esophageal cancer with gene expression analysis.

PURPOSE: To determine the maximal tolerated dose of capecitabine with oxaliplatin + radiotherapy in a phase I study of localized esophageal cancer. PATIENTS AND METHODS: Oxaliplatin (85 mg/m(2)) administered on days 1, 15, and 29. Capecitabine administered twice daily 5 days weekly; dose levels (DL) were 1, 1000; 2, 1250; and 3, 1500 mg/m(2) with 50.4 Gy radiation. RESULTS: Dose-limiting toxicity was reached at DL 3. Carboxylesterase expression in day 2 tumor specimens and induction correlated with response (p

Intraoperative sentinel node mapping with technitium-99 in lung cancer: results of CALGB 140203 multicenter phase II trial.

INTRODUCTION: Sentinel node mapping with radioactive technetium in non-small cell lung cancer has been shown to be feasible in several single institution reports. The Cancer and Leukemia Group B designed a phase II trial to test a standardized method of this technique in a multi-institutional setting. If validated, the technique could provide a more accurate and sensitive way to identify lymph node metastases. METHODS: Patients with clinical stage I non-small cell lung cancer amenable to resection were candidates for this trial. Intraoperatively, tumors were injected with technetium sulfur colloid (0.25 mCi). The tumor and lymph nodes were measured in vivo with a hand held Geiger counter and resection of the tumor and nodes was carried out. Sentinel nodes, all other nodes and the tumor were analyzed with standard histologic assessment. Negative sentinel nodes were also evaluated with immunohistochemistry. RESULTS: In this phase II trial, 8 surgeons participated (1-13 patients enrolled per surgeon), and 46 patients (out of a planned 150) were enrolled. Of these, 43 patients had cancer and an attempted complete resection, and 39 patients underwent sentinel node mapping. One or more sentinel nodes were identified in 24 of the 39 patients (61.5%). The sentinel node(s) were found to be accurate (no other nodes were positive for cancer if the sentinel node was negative) in 20/24 patients (83.3%). In the overall group the sentinel node mapping procedure was found to be accurate in 20/39 patients (51.2%). CONCLUSIONS: Intraoperative sentinel node mapping in lung cancer with radioisotope yielded lower accrual and worse accuracy than expected. The multi-institutional attempt at validating this technique was unsuccessful.

Concurrent oxaliplatin, 5-fluorouracil, and radiotherapy in the treatment of locally advanced esophageal carcinoma.

PURPOSE: The combination of oxaliplatin, 5-fluorouracil, and leucovorin with concurrent radiotherapy was demonstrated to be a safe regimen for locally advanced esophageal carcinoma in a prior phase I study. We now report the efficacy data for 42 patients treated with this regimen. METHODS: Each chemotherapy cycle lasted 29 days and consisted of 5-fluorouracil, 180 mg/m2 protracted-infusion from days 1 to 29, and oxaliplatin, 85 mg/m2 on days 1, 15, and 29. The first cycle was administered concurrently with radiation. The radiation field included regional lymph nodes as well as the primary tumor or tumor bed to a dose of 50.4 Gy in 28 fractions. After concurrent chemoradiotherapy, 1 to 2 additional cycles of chemotherapy were administered. If esophagectomy was indicated, it occurred 4 weeks after completion of concurrent chemoradiotherapy. In the adjuvant group, concurrent chemoradiotherapy was initiated 4 weeks after surgery. RESULTS: Median age was 61 years (range 38-78 years); 30 (71%) of the patients were male. Thirty-three patients had adenocarcinoma, and 9 had squamous cell carcinoma. Concurrent chemoradiotherapy was administered preoperatively (group 1) in 24 patients, definitively (group 2) in 13 patients, and as adjuvant treatment (group 3) in 5 patients. In group 1, 16 patients were down-staged including 1 patient with minimal residual disease and 5 with a complete pathologic response; 4 patients were not down-staged, and 4 did not undergo esophagectomy (2 progressed, 1 died of unrelated causes, and 1 refused). In group 2, 1 patient had a complete clinical response, 4 others were down-staged, 2 had stable disease, and 6 progressed. Four patients in group 3 progressed. Median survival was 28 months for group 1, 12 months for group 2, and not reached at 14 months for group 3. There was one grade 4 toxicity (anaphylaxis) in group 2. Grade 3 toxicities were reported for 5 patients in group 1 and 1 patient in group 2. They consisted of hypotension (n=1), fatigue (n=2), diarrhea (n=2), neuropathy (n=1), mucositis (n=1), pneumonitis (n=1), dehydration (n=1), emesis (n=1), and weight loss (n=1). CONCLUSIONS: Our study supports the incorporation of oxaliplatin into a multimodal concurrent chemoradiotherapy protocol for locally advanced esophageal cancer.

Radioguided detection of lymph node metastasis in non-small cell lung cancer.

BACKGROUND: The detection of micrometastases in thoracic lymph nodes may improve the staging of non-small cell lung cancer patients. METHODS: Ten patients with resectable lung cancers were enrolled in this pilot study. Every patient had preoperative positron emission tomography (PET) imaging and mediastinoscopy. Patients were injected with 10 mCi of F18-fluorodeoxyglucose (FDG) on the day of surgery, within 4 hours of the planned surgical procedure. A handheld device detected increased FDG uptake (gamma emission) within thoracic lymph nodes during pulmonary resection procedures. The lymph nodes that demonstrated increased FDG uptake, but were nonmalignant by conventional hematoxylin and eosin staining, underwent further serial sectioning and immunohistochemical staining. RESULTS: The handheld probe detected all FDG-avid lesions on PET imaging. In 3 patients (30%), the probe led to the detection of FDG-avid lymph nodes harboring micrometastases missed by conventional pathologic analysis. A fourth patient had aortopulmonary nodes that were FDG-avid on PET and showed metastases by hematoxylin and eosin staining, but the probe detected adjacent nodes in the same station with micrometastases. Three nodes were false-positive by gamma probe. CONCLUSIONS: It is feasible to detect occult metastases in lymph nodes by using an FDG-sensitive intraoperative gamma probe, resulting in upstaging of patients. A larger study is indicated to evaluate the sensitivity, specificity, and clinical utility of such a device.

Chylothorax.

Chylothorax is a rare complication of pulmonary resection. It requires prompt treatment, which is initially conservative. This treatment consists of drainage, nutritional support, and measures to diminish chyle flow. Surgical intervention is indicated when conservative management is ineffective. Delay in surgical intervention leads not only to serious metabolic, nutritional, and immunologic disturbances from the loss of chyle but also increases the risk for adhesion formation, loculation, organization, and infection of the chylothorax, making subsequent surgical attempts difficult and increasing postoperative morbidity and mortality. VATS provides a minimally invasive approach for the treatment of chylothorax complicating pulmonary resection. Clipping of the thoracic duct or chemical pleurodesis may be performed with minimal morbidity and mortality. Conservative treatment is expensive and fails in most patients who have high-output chylous fistulae. On the other hand, VATS is uniformly effective, is less expensive, and has low morbidity. Indeed, VATS is rapidly becoming the preferred approach for the management of chylothorax complicating pulmonary resection. The need to prevent the occurrence of a chylothorax by careful dissection techniques and liberal clipping of lymphatic vessels particularly in areas of high anatomic risk during the initial operation cannot be overemphasized.

Minimally invasive pneumonectomy.

Technical advances have resulted in the growing popularity and success of video-assisted thoracoscopic lobectomy for the treatment of nonsmall cell lung cancer. Several investigators have used similar techniques to safely perform pneumonectomies. Minimally invasive pneumonectomy may be indicated for patients who have centrally located malignant lesions and who are not candidates for sleeve resections. Adequate exposure of the proximal hilar vessels is mandatory. Short-term results are encouraging, but prospective long-term data are essential.