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Biomedical subjects

Valerie W Rusch

Publications and source records attributed to Valerie W Rusch.

At least 19 recordsLinked to original sources

Lymphadenectomy for adenocarcinoma of the gastroesophageal junction (GEJ): impact of adequate staging on outcome.

INTRODUCTION: Adequate staging of gastric cancer requires examination of at least 15 lymph nodes. Most resected patients are inadequately staged potentially confounding the interpretation of clinical data. The aim of this study was to determine whether adequate staging revealed different prognostic factors or improved survival compared with patients with <15 nodes examined after R0 resection for GEJ cancer. METHODS: A prospectively maintained database identified 366 patients with Siewert types II and III adenocarcinoma of the GEJ who underwent R0 resection without neoadjuvant therapy at a single institution. Patients were grouped into adequately (>or=15 nodes examined) or inadequately staged (<15 nodes examined). Median follow up was 51 months. RESULTS: From 1985 through 2003, 250/366 (68%) patients were adequately staged and 116/366 (32%) were inadequately staged. There was no difference in operative mortality between adequately staged (5.2%) and inadequately staged patients (4.3%, P = NS). Adequately staged patients had more positive lymph nodes (median 2) compared with inadequately staged patients (median 1, P < 0.01). Multivariable analysis of adequately staged patients found the number of positive lymph nodes, T stage, and lymphovascular invasion to be independent prognostic factors for overall survival (OS). For inadequately staged patients only the number of positive lymph nodes and T stage were independent prognostic factors. Adequate staging was an independent prognostic factor for patients with advanced (T >or= 2 Nany) tumors. For T1 tumors adequate staging was not associated with improved survival. CONCLUSIONS: Patients with GEJ cancer should undergo adequate lymphadenectomy to permit examination of >or=15 lymph nodes allowing the accurate identification of prognostic variables. Removal of >or=15 lymph nodes is associated with more accurate survival estimates for patients with advanced disease.

Adenocarcinoma↗

Radiation-induced cellular DNA damage repair response enhances viral gene therapy efficacy in the treatment of malignant pleural mesothelioma.

BACKGROUND: Malignant pleural mesothelioma (MPM) treated with radiotherapy (RT) has incomplete responses as a result of radiation-induced tumoral stress response that repairs DNA damage. Such stress response is beneficial for oncolytic viral therapy. We hypothesized that a combination of RT and NV1066, an oncolytic herpes virus, might exert an additive or synergistic effect in the treatment of MPM. METHODS: JMN, a MPM cell line, was infected with NV1066 at multiplicities of infection of .05 to .25 in vitro with and without radiation (1 to 5 Gy). Virus replication was determined by plaque assay, cell kill by lactate dehydrogenase assay, and GADD34 (growth arrest and DNA damage repair 34, a DNA damage-repair protein) by real-time reverse transcriptase-polymerase chain reaction and Western blot test. Synergistic cytotoxicity dependence on GADD34 upregulation was confirmed by GADD34 small inhibitory RNA (siRNA). RESULTS: Synergism was demonstrated between RT and NV1066 across a wide range of doses. As a result of such synergism, a dose-reduction for each agent (up to 5500-fold) can be accomplished over a wide range of therapeutic-effect levels without sacrificing tumor cell kill. This effect is correlated with increased GADD34 expression and inhibited by transfection of siRNA directed against GADD34. CONCLUSIONS: RT can be combined with oncolytic herpes simplex virus therapy in the treatment of malignant pleural mesothelioma to achieve synergistic efficacy while minimizing dosage and toxicity.

Animals↗

Acupuncture is a feasible treatment for post-thoracotomy pain: results of a prospective pilot trial.

BACKGROUND: Thoracotomy is associated with severe pain that may persist for years. Acupuncture is a complementary therapy with a proven role in pain control. A randomized trial showed that acupuncture was effective in controlling pain after abdominal surgery, but the efficacy of this technique for the treatment of thoracotomy pain has not been established. We developed a novel technique for convenient application of acupuncture to patients undergoing thoracotomy, and in a Phase II trial evaluated the safety of this intervention and the feasibility of doing a randomized trial. METHODS: Adult patients scheduled for unilateral thoracotomy with preoperative epidural catheter placement received acupuncture immediately prior to surgery. Eighteen semi-permanent intradermal needles were inserted on either side of the spine, and four were inserted in the legs and auricles. Needles were removed after four weeks. Using a numerical rating scale, pain was measured on the first five postoperative days. After discharge, pain was assessed using the Brief Pain Inventory at 7, 30, 60 and 90 days. RESULTS: Thirty-six patients were treated with acupuncture. Of these, 25, 23, and 22 patients provided data at 30, 60, and 90 days, respectively. The intervention was well tolerated by patients with only one minor and transient adverse event of skin ulceration. CONCLUSION: The rate of data completion met our predefined criterion for determining a randomized trial to be feasible (at least 75% of patients tolerated the intervention and provided evaluable data). This novel intervention is acceptable to patients undergoing thoracotomy and does not interfere with standard preoperative care. There was no evidence of important adverse events. We are now testing the hypothesis that acupuncture significantly adds to standard perioperative pain management in a randomized trial.

Journal Article↗

Use of cigarette-smoking history to estimate the likelihood of mutations in epidermal growth factor receptor gene exons 19 and 21 in lung adenocarcinomas.

PURPOSE: Lung adenocarcinomas with mutations in exons 19 and 21 of the epidermal growth factor receptor gene (EGFR) demonstrate sensitivity to gefitinib or erlotinib. Investigators have reported an association between EGFR mutations and the amount and duration of cigarette smoking, with the highest incidence of mutations seen in never smokers. METHODS: EGFR exon 19 and 21 mutation status was determined in 265 tumor samples using direct sequencing, polymerase chain reaction (PCR), or PCR-based restriction fragment length polymorphism analysis. A detailed smoking history was obtained. Patients were categorized as never smokers (< 100 lifetime cigarettes), former smokers (quit > or = 1 year ago), or current smokers (quit < 1 year ago). RESULTS: We detected EGFR mutations in 34 (51%) of 67 never smokers (95% CI, 38% to 64%), 29 (19%) of 151 former smokers (95% CI, 13% to 27%), and two (4%) of 47 current smokers (95% CI, 1% to 16%). Significantly fewer EGFR mutations were found in people who smoked for more than 15 pack-years (P < .001) or stopped smoking less than 25 years ago (P < .02) compared with individuals who never smoked. The number of smoking pack-years and smoke-free years predicted the prevalence of EGFR mutations (areas under receiver operating characteristic curve = 0.78 and 0.77, respectively). CONCLUSION: The likelihood of EGFR mutations in exons 19 and 21 decreases as the number of pack-years increases. Mutations were less common in people who smoked for more than 15 pack-years or who stopped smoking cigarettes less than 25 years ago. These data can assist clinicians in assessing the likelihood of exon 19 and 21 EGFR mutations in patients with lung adenocarcinoma when mutational analysis is not feasible.

Adenocarcinoma↗

Real-time diagnostic imaging of tumors and metastases by use of a replication-competent herpes vector to facilitate minimally invasive oncological surgery.

Current efforts on expanding minimally invasive techniques into the realm of oncological surgery are hindered by lack of accurate visualization of tumor margins and failure to detect micro metastases in real time. We used a systemic delivery of a herpes viral vector with cancer-selective infection and replication to precisely differentiate between normal and malignant tissue. NV1066 is a genetically modified, replication-competent herpes simplex virus carrying a transgene for enhanced green fluorescent protein (GFP). We tested the potential of NV1066 in delineating tumor tissue in vitro and in vivo in a wide range of cancers and whether NV1066-induced GFP expression can detect small foci of tumors and metastases in in vivo models using an operating endoscope with fluorescent filters. Our findings indicate that NV1066 can be used for real-time intraoperative imaging and enhanced detection of early cancers and metastases. We demonstrate that a single dose of NV1066, administered either locally (intratumoral or intracavitary) or systemically, will detect loco-regional and distant disease throughout the body. Such cancer selectivity is confirmed in 110 types of cancer cells from 16 different primary organs. Fluorescence-aided minimally invasive endoscopy revealed microscopic tumor deposits unrecognized by conventional laparoscopy/thoracoscopy. Furthermore, NV1066 ability to transit and infect tumor and metastases is proven in syngenic and transplanted tumors in different animal models, both immunocompetent and immunodeficient. Cancer-selective GFP expression is confirmed by histology, immunohistochemistry, and qRT-PCR. These studies form the basis for real-time, intraoperative diagnostic imaging of tumor and metastases by minimally invasive endoscopic technology.

Animals↗

Cisplatin-induced GADD34 upregulation potentiates oncolytic viral therapy in the treatment of malignant pleural mesothelioma.

BACKGROUND: NV1066, a replication-competent oncolytic herpes simplex virus type 1 (HSV-1) attenuated by a deletion in the gene gamma(1)34.5, preferentially replicates in and kills malignant cells. gamma(1)34.5 encodes ICP34.5, a viral protein essential for productive replication, which has homology with mammalian stress response induced GADD34 (growth arrest and DNA damage-inducible protein). We hypothesized that cisplatin upregulates GADD34 expression, which enhances NV1066 replication and oncolysis. METHODS: Ten human malignant pleural mesothelioma (MPM) cell lines were infected with NV1066 at multiplicities of infection (MOI; ratio of viral particles per tumor cell) 0.005 to 0.8 in vitro, with and without cisplatin (1 to 4 microM). In the MPM cell line VAMT, viral replication was determined by plaque assay, cell kill by lactate dehydrogenase assay, and GADD34 induction by quantitative RT-PCR and Western blot. Synergistic efficacy was confirmed by the isobologram and combination index methods of Chou-Talalay. GADD34 upregulation by cisplatin was inhibited with GADD34 siRNA to further confirm the synergistic efficacy dependence with GADD34. RESULTS: Combination therapy with NV1066 and cisplatin showed strong synergism in epithelioid (H-2452, H-Meso), sarcomatoid (H-2373, H-28), and biphasic (JMN, Meso-9, MSTO-211H) MPM cell lines, and an additive effect in others. In VAMT cells combination therapy enhanced viral replication 4 to 11-fold (p < 0.01) and cell kill 2 to 3-fold (p < 0.01). Significant dose reductions for both agents (2 to 600-fold) were achieved over a wide range of therapeutic-effect levels (LD50-LD99) without compromising cell kill. Synergistic cytotoxicity correlated with GADD34 upregulation (2 to 4-fold, p < 0.01) and was eliminated following transfection with GADD34 siRNA. CONCLUSION: Cisplatin-induced GADD34 expression selectively enhanced the cytotoxicity of the gamma(1)34.5-deficient oncolytic virus, NV1066. This provides a cellular basis for combination therapy with cisplatin and NV1066 to treat MPM and achieve synergistic efficacy, while minimizing dosage and toxicity.

Antigens, Differentiation↗

Imaging and therapy of malignant pleural mesothelioma using replication-competent herpes simplex viruses.

BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive cancer that is refractory to current treatment modalities. Oncolytic herpes simplex viruses (HSV) used for gene therapy are genetically engineered, replication-competent viruses that selectively target tumor cells while sparing normal host tissue. The localized nature, the potential accessibility and the relative lack of distant metastasis make MPM a particularly suitable disease for oncolytic viral therapy. METHODS: The infectivity, selective replication, vector spread and cytotoxic ability of three oncolytic HSV: G207, NV1020 and NV1066, were tested against eleven pathological types of MPM cell lines including those that are resistant to radiation therapy, gemcitabine or cisplatin. The therapeutic efficacy and the effect on survival of NV1066 were confirmed in a murine MPM model. RESULTS: All three oncolytic HSV were highly effective against all the MPM cell lines tested. Even at very low concentrations of MOI 0.01 (MOI: multiplicity of viral infection, ratio of viral particles per cancer cell), HSV were highly effective against MPM cells that are resistant to radiation, gemcitabine and cisplatin. NV1066, an oncolytic HSV that expresses green fluorescent protein (GFP), was able to delineate the extent of the disease in a murine model of MPM due to selective infection and expression of GFP in tumor cells. Furthermore, NV1066 was able to reduce the tumor burden and prolong survival even when treatment was at an advanced stage of the disease. CONCLUSION: These findings support the continued investigation of oncolytic HSV as potential therapy for patients with therapy-resistant MPM.

Animals↗

Morbidity and mortality of major pulmonary resections in patients with early-stage lung cancer: initial results of the randomized, prospective ACOSOG Z0030 trial.

BACKGROUND: Little prospective, multiinstitutional data exist regarding the morbidity and mortality after major pulmonary resections for lung cancer or whether a mediastinal lymph node dissection increases morbidity and mortality. METHODS: Prospectively collected 30-day postoperative data was analyzed from 1,111 patients undergoing pulmonary resection who were enrolled from July 1999 to February 2004 in a randomized trial comparing lymph node sampling versus mediastinal lymph node dissection for early stage lung cancer. RESULTS: Of the 1,111 patients randomized, 1,023 were included in the analysis. Median age was 68 years (range, 23 to 89 years); 52% were men. Lobectomy was performed in 766 (75%) and pneumonectomy in 42 (4%). Pathologic stage was IA in 424 (42%), IB in 418 (41%), IIA in 37 (4%), IIB in 97 (9%), and III in 45 (5%). Lymph node sampling was performed in 498 patients and lymph node dissection in 525. Operative mortality was 2.0% (10 of 498) for lymph node sampling and 0.76% (4 of 525) for lymph node dissection. Complications occurred in 38% of patients in each group. Lymph node dissection had a longer median operative time and greater total chest tube drainage (15 minutes, 121 mL, respectively). There was no difference in the median hospitalization, which was 6 days in each group (p = 0.404). CONCLUSIONS: Complete mediastinal lymphadenectomy adds little morbidity to a pulmonary resection for lung cancer. These data from a current, multiinstitutional cohort of patients who underwent a major pulmonary resection constitute a new baseline with which to compare results in the future.

Adult↗

Results of chest wall resection and reconstruction with and without rigid prosthesis.

BACKGROUND: Chest wall resections are associated with significant morbidity, with respiratory failure in as many as 27% of patients. We hypothesized that our selective use of a rigid prosthesis for reconstruction reduces respiratory complications. METHODS: The records of all patients undergoing chest wall resection and reconstruction were reviewed. Patient demographics, use of preoperative therapy, the location and size of the chest wall defect, performance of lung resection if any, the type of prosthesis, and postoperative complications were recorded. Predictor of complications were identified by chi2 and logistic regression analyses. RESULTS: From January 1, 1995, to July 1, 2003, 262 patients (median age, 60 years) underwent chest wall resection for tumor in 251 (96%), radiation necrosis in 7 (2.7%); and infection in 4 patients (1.3%). The median defect size was 80 cm2 (range, 2.7 to 1,200 cm2) and the median number of ribs resected was 3 (range, 1 to 8). Major lung resection was performed in 85 patients (34%). Prosthetic reconstruction was rigid (polypropylene mesh/methylmethacrylate composite) in 112 (42.7%), nonrigid (polytetrafluoroethylene or polypropylene mesh) in 97 (37%), and none in 53 patients. Postoperatively, 10 patients died (3.8%), 4 of whom had pneumonectomy plus chest wall resection. Respiratory failure occurred in 8 patients (3.1%). By multivariate analysis, the size of the chest wall defect was the most significant predictor of complications. CONCLUSIONS: Our incidence of respiratory failure is lower than previously reported and may relate to our use of rigid repair for defects likely to cause a flail segment. Pneumonectomy plus chest wall resection should be performed only in highly selected patients.

Adult↗

Mortality increases for octogenarians undergoing esophagogastrectomy for esophageal cancer.

BACKGROUND: As the general population ages, it becomes increasingly important to understand the potential contribution of chronologic age to mortality after esophagectomy. Because this risk is poorly defined, we sought to determine whether extreme age (>80 years) is an independent risk factor after esophagectomy. METHODS: We analyzed a prospectively maintained, single-institution database of 858 consecutive patients who underwent esophagectomy between January 1996 and May 2005. Data evaluated included patient demographics, medical comorbidity, types of resections performed, length of stay, postoperative adverse events, and overall survival. We used univariate, multivariate, and Kaplan-Meier analysis to determine the influence of age on postoperative morbidity, in-hospital survival, and overall survival. RESULTS: Of 858 patients, 31 (10 female, 21 male) were older than 80 years of age. Preliminary analysis indicated that patients younger than 50 years (n = 107) had significantly fewer comorbidities; these were excluded from the analysis. In the remaining 751 patients, the age older than 80 cohort was compared with patients aged 50 to 79. Patients aged 50 to 79 were grouped because of similar characteristics (length of stay, hospital death). There were no significant differences in comorbidities, types of resections, or postoperative complication type or severity between the two groups. Postoperative death, length of stay, and survival, however, were significantly worse in patients older than 80. In a logistic regression model controlling for comorbidity, age older than 80 was significantly associated with increased perioperative mortality (hazard-ratio, 3.9; p < 0.01). CONCLUSIONS: Patients older than 80 years have increased mortality risk after esophagectomy, independent of comorbidity. Octogenarian status should be a consideration in the management of these patients.

Age Factors↗

Extrapleural pneumonectomy in children.

BACKGROUND/PURPOSE: Extrapleural pneumonectomy (EPP) is an en bloc resection of the pleura, lung, diaphragm, and pericardium. EPP in the pediatric population has not been reported in the literature. We report our experience of using EPP in children to treat a variety of malignancies that involve the pleural surface. METHODS: We performed a retrospective review of all children treated through EPP at our institution. Data were obtained from patient charts and a pediatric database. All patients underwent en bloc resection of the pleura, lung, diaphragm, and pericardium and reconstruction. RESULTS: Four patients underwent EPP from 2000 to 2004 for inflammatory myofibroblastic tumor, spindle cell sarcoma, metastatic neuroblastoma, and malignant mesothelioma. The patients' ages were from 6 to 11 years. The patient with metastatic neuroblastoma had recurrent disease in the left chest 1 year after EPP and died of sepsis; the patient with mesothelioma died of disease extension into the abdomen 1.5 years later. The other 2 patients are free of disease. CONCLUSIONS: EPP can be performed with curative intent in selected pediatric patients with pleural-based malignancies. EPP should be included in the armamentarium of the pediatric thoracic surgeon and evaluated in larger studies.

Abdominal Neoplasms↗

Robotic assistance for video-assisted thoracic surgical lobectomy: technique and initial results.

OBJECTIVES: There is little experience with telerobotic assistance for video-assisted thoracic surgical lobectomy. We developed a technique for robotic assistance during video-assisted thoracic surgical lobectomy and report our initial results. METHODS: Video-assisted thoracic surgical lobectomy with the da Vinci Surgical System (Intuitive Surgical, Sunnyvale, Calif) was attempted in 34 patients (median age, 69.0 years; age range, 12-85 years). Robotic instruments were used for individual dissection of the hilar structures through 2 thoracoscopic ports and a 4-cm utility incision without rib spreading. Data on patient characteristics and perioperative results were collected prospectively. RESULTS: Robot-assisted video-assisted thoracic surgical lobectomy was accomplished in 30 patients (19 female and 11 male patients). Every type of lobectomy was performed. Four (4/34 [12%]) patients required conversion to thoracotomy. The majority of patients had non-small cell lung cancer (32/34 [94%]), and 1 patient each had a typical carcinoid tumor and an extranodal B-cell lymphoma. Every patient underwent an R0 resection. The median number of lymph node stations dissected with robotic assistance was 4 (range, 2-7). Operative mortality was 0%, with no in-hospital or perioperative deaths. Nine (26%) patients experienced National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0 grade 2 or 3 complications. The median chest tube duration was 3.0 days (range, 2-12 days), and the median length of stay was 4.5 days (range, 2-14 days). The median operative time was 218 minutes (range, 155-350 minutes). CONCLUSIONS: Robot assistance for video-assisted thoracic surgical lobectomy is feasible and safe. The utility and advantages of robotic assistance for video-assisted thoracic surgical lobectomy require further refinement and study of the technique.

Adolescent↗

Positron emission tomography predicts survival in malignant pleural mesothelioma.

OBJECTIVES: Recent studies suggest that standard uptake value on fluorodeoxyglucose positron emission tomography scan can predict mediastinal lymph node status in malignant pleural mesothelioma. Because mediastinal nodal metastasis is known to be associated with poor prognosis, we hypothesized that standard uptake value on fluorodeoxyglucose positron emission tomography might independently predict survival. METHODS: Patients with pathologically proven mesothelioma underwent fluorodeoxyglucose positron emission tomography scanning. Patients fasted and received a minimum of 10 mCi of F18-fluorodeoxyglucose. Whole-body emission studies were acquired, followed by whole-body transmission scans with iterative reconstruction. On the basis of the maximal chi-square method, a standard uptake value of 10 was chosen to classify patients as low versus high standard uptake value. Survival probabilities for both standard uptake value groups were estimated by the Kaplan-Meier method. A Cox proportional hazards model assessed the joint influence of standard uptake value, histology, and stage on survival. RESULTS: From 1998 to 2005, 137 patients with malignant pleural mesothelioma underwent positron emission tomography scans. The median follow-up for all surviving patients was 24 months. Median survivals were 9 and 21 months for the high and low standard uptake value groups, respectively (P = .02). In a multivariable analysis, high standard uptake value tumors were associated with a 1.9 times greater risk of death than low standard uptake value tumors (P < .01). Mixed histology carried a 2.9 times greater risk of death than epithelioid histology (P < .01), and stages III and IV had a 1.8 times greater risk of death than stages I and II (P = .05). CONCLUSIONS: Standard uptake value greater than 10, mixed histology, and stages III and IV are poor risk factors in malignant pleural mesothelioma. These findings suggest that fluorodeoxyglucose positron emission tomography can be used to stratify patients for treatment and clinical trials.

Adult↗

Intraoperative localization of lymph node metastases with a replication-competent herpes simplex virus.

OBJECTIVES: Lymph node status is the most important prognostic factor determining recurrence and survival in patients with mesothelioma and other thoracic malignancies. Accurate localization of lymph node metastases is therefore necessary to improve selection of resectable and curable patients for surgical intervention. This study investigates the potential to identify lymph node metastases intraoperatively by using herpes-guided cancer cell-specific expression of green fluorescent protein. METHODS: After infection with NV1066, a herpes simplex virus carrying green fluorescent protein transgene, human mesothelioma cancer cell lines were assessed for cancer cell-specific infection, green fluorescent protein expression, viral replication, and cytotoxicity. Murine models of lymphatic metastasis were established by means of surgical implantation of cancer cells into the preauricular (drainage to cervical lymph nodes) and pleural (mediastinal and retroperitoneal lymph nodes) spaces of athymic mice. Fluorescent thoracoscopy, laparoscopy, and stereomicroscopy were used to localize lymph node metastases that were confirmed by means of immunohistochemistry. RESULTS: In vitro NV1066 infected, replicated (5- to 17,000-fold), and expressed green fluorescent protein in all cancer cells, even when infected at a low ratio of one viral plaque-forming unit per 100 tumor cells. In vivo NV1066 injected into primary tumors was able to locate and infect lymph node metastases producing green fluorescent protein that was visualized by means of fluorescent imaging. Histology confirmed lymphatic metastases, and immunohistochemistry confirmed viral presence in regions that expressed green fluorescent protein. CONCLUSIONS: Herpes virus-guided cancer cell-specific production of green fluorescent protein can facilitate accurate localization of lymph node metastases. Fluorescent filters that detect green fluorescent protein can be incorporated into operative scopes to precisely localize and biopsy lymph node metastases.

Animals↗

Management of Pancoast tumours.

Non-small-cell lung carcinomas of the superior sulcus, frequently termed Pancoast tumours, are some of the most challenging thoracic malignant diseases to treat because of their proximity to vital structures at the thoracic inlet. Originally deemed universally fatal, Pancoast tumours are now amenable to curative treatment because of improvements in combined modality therapy and development of new techniques for resection. This review includes discussion of anatomical considerations, initial assessment, multimodality treatment, and surgical approaches for these cancers.

Combined Modality Therapy↗

Yield of brain 18F-FDG PET in evaluating patients with potentially operable non-small cell lung cancer.

UNLABELLED: The American College of Surgeons Oncology Group recently completed a trial evaluating the role of PET with 18F-FDG in patients with documented or suspected non-small cell lung cancer. Subjects underwent standard imaging to exclude metastatic disease before PET. Here, we report the yield of brain PET in evaluating, for potential intracranial metastases, patients who have undergone previous brain CT or MRI with negative findings. METHODS: A total of 287 evaluable patients who had been registered from 22 institutions underwent whole-body 18F-FDG PET, including dedicated PET of the brain, after routine staging procedures had found no suggestion of metastatic disease. Patients were followed postoperatively for disease-free and overall survival, with a minimum follow-up of 6 mo. Patients with specific brain abnormalities identified by PET were further examined, and the findings were evaluated along with the results of CT and MRI, clinical management, and follow-up. RESULTS: In 4 patients, PET found focal 18F-FDG uptake in the brain suggestive of metastatic disease; however, metastatic disease was excluded clinically in all 4 by negative findings on further brain imaging. All 4 patients remained alive at follow-up (mean duration, 10.5 mo; range, 6-16 mo). CONCLUSION: In patients with suspected or proven non-small cell lung cancer considered resectable by standard imaging, including routine preoperative contrast-enhanced CT or MRI of the brain, PET of the brain provides no additional information regarding metastatic disease.

Aged↗

Hemithoracic radiation therapy after pleurectomy/decortication for malignant pleural mesothelioma.

PURPOSE: To evaluate pleurectomy/decortication (P/D) and adjuvant radiotherapy (RT) in the treatment of malignant pleural mesothelioma (MPM). METHODS AND MATERIALS: In a retrospective review, we included MPM patients treated with P/D and adjuvant RT at Memorial Sloan-Kettering Cancer Center from 1974 to 2003. When indicated, patients received intraoperative brachytherapy to residual tumor. RESULTS: All 123 patients received external beam RT (median dose, 42.5 Gy; range, 7.2-67.8 Gy) to the ipsilateral hemithorax postoperatively. Fifty-four patients underwent brachytherapy (matched peripheral dose, 160 Gy). The median and 2-year overall survival for all patients was 13.5 months (range, 1-199 months) and 23%, respectively. One-year actuarial local control for all patients was 42%. Multivariate analysis for overall survival revealed radiation dose <40 Gy (p = 0.001), nonepithelioid histology (p = 0.002), left-sided disease (p = 0.01), and the use of an implant (p = 0.02) to be unfavorable. Two patients (1.6%) died from Grade 5 toxicity within 1 month of treatment. CONCLUSIONS: Pleurectomy/decortication with adjuvant radiotherapy is not an effective treatment option for patients with MPM. Our results imply that residual disease cannot be eradicated with external RT with or without brachytherapy and that a more extensive surgery followed by external RT might be required to improve local control and overall survival.

Adult↗