Stereotactic radiosurgery for thoracic malignancies

Radiosurgery for lung cancer is a novel and promising concept that warrants thorough review. Stereotactic body radiotherapy enables the selective delivery of an intense dose of high-energy radiation to destroy a tumor with precise targeting. The radiobiology and physics behind the use of radiosurgery are presented, followed by a discussion of promising retrospective and prospective clinical data that has been reported from Japan, Europe, and the United States. The article closes with a discussion of multidisciplinary approaches that include radiosurgery which are on the therapeutic horizon.     

Extrapleural pneumonectomy for thoracic malignancies

Extrapleural pneumonectomy has been used by thoracic surgeons in the treatment of malignant pleural mesothelioma as well as other pleural diseases, such as tuberculous empyema. Recently, this operative procedure has been also sporadically applied for the treatment of carcinomatous pleuritis of lung cancer and/or invasive thymoma in some institutions. We performed this operation in 24 patients with thoracic malignancy: 15 patients with carcinomatous pleuritis of primary lung adenocarcinoma (6 patients with T4N0 disease, 2 with T4N1, and 7 with T4N2), 3 patients with stage IV a thymoma, and 6 patients with malignant pleural mesothelioma (2 patients with stage II disease, 3 with stage III, and 1 with stage IV). All patients survived the operation and were discharged from the hospital. Major complications were intrathoracic hemorrhage and empyema in 2 patients each. The median survival time and 5-year survival rate of lung cancer patients were 34 months and 45.5%, respectively. All patients with thymoma are alive now without disease 9 to 133 months after operation. All patients with malignant pleural mesothelioma except 1, who lately underwent this treatment, died of disease from 15 to 27 months after surgery. Our results indicate that carefully selected patients with carcinomatous pleuritis of lung cancer and thymoma may be candidates for extrapleural pneumonectomy for cure. Nevertheless, the ultimate value of this surgical treatment should be ascertained in a prospective study with a large number of patients.     

Immunotherapy of human malignancies with immune RNA

Immune RNA (I-RNA) is an RNA-rich nucleic acid preparation extracted from lymphoid cells or tissues following exposure to specific antigens in vitro or sensitization to specific antigens in vivo. It has been shown to induce normal, nonimmune lymphoid cells to mediate specific cellular and humoral immune responses in vitro and in vivo. Previous studies have demonstrated that I-RNA preparations extracted from the lymphoid organs of animals immunized with tumor cells mediate specific immune responses against tumor associated antigens in both animal models and human tumor systems. Based on this work, preliminary clinical trials of I-RNA immunotherapy were initiated 3 years ago. Cancer patients were treated with I-RNA extracted from the lymphoid organs of sheep immunized with either autologous tumor cells or allogeneic tumor cells of the same histologic type. I-RNA was administered weekly, intradermally, at doses of 4 to 8 mg/week without any significant local or systemic toxicity. The results of these preliminary trials suggest increased survival in patients with metastatic hypernephroma and possible benefit in the form of decreased recurrence rate in the adjuvant immunotherapy of patients with malignant melanoma. A prospectively randomized trial of adjuvant immunotherapy with I-RNA in patients with Dukes' classes B₂ and C colorectal cancer has been recently undertaken.

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Résumé Le RNA immun (I-RNA) est une préparation d'acides nucléiques riche en RNA, extraite de cellules ou tissus lymphoÏdes préalablement exposés in vitro ou sensibilisés in vivo à des antigènes spécifiques. Il a été prouvé qu'il rend les cellules lymphoÏdes vierges capables de déclencher, in vitro et in vivo, des réponses immunologiques cellulaires et humorales spécifiques. Des travaux antérieurs ont démontré que des préparations d'I-RNA, extraites d'organes lymphoÏdes d'animaux immunisés par des cellules tumorales, sont capables de transférer, tant chez l'animal que chez l'homme, les réponses immunologiques spécifiques contre les antigènes associés aux tumeurs. A la suite de ces travaux, des essais cliniques préliminaires d'immunothérapie par l'I-RNA ont été entamées il y a 3 ans. Des malades atteints de cancer ont été traités avec du I-RNA extrait d'organes lymphoÏdes de moutons immunisés avec des cellules tumorales, autologues ou homologues, de mÊme type histologique. L'I-RNA a été administré par voie intradermique, à la dose de 4–8 mgr/semaine, sans aucun effet toxique local ou systémique. Les résultats de ces études préliminaires semblent indiquer une prolongation de la survie dans des cas d'hypernéphrome avec metastases et un effet bénéfique (réduction de la fréquence des récidives) lorsque l'I-RNA est utilisé comme immunothérapie adjuvante en cas de mélanome malin. Récemment, une étude prospective randomisée a été entreprise avec I-RNA comme immunothérapie adjuvante dans des cas de cancer du colon et du rectum aux stades Dukes B2 et C.

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Supported in part by grants number CA-21664, CA-12582, C A-16402, and NIH-4-444992-32691 from the National Institutes of Health and by grant number 1797-03 from the Veterans Administration.     

Radionuclide imaging of thoracic malignancies

Over the past decade a variety nuclear medicine imaging studies have become available that are of considerable value to patients who have pulmonary malignancies. By far the greatest impact on the management of patients who have thoracic malignancy has been the availability of 18FDG-PET imaging. In the patient who has newly diagnosed lung carcinoma, 18FDG-PET improves the accuracy of staging the disease by identifying or excluding mediastinal disease and distant metastatic foci. 18FDG-PET is superior to anatomic methods for evaluating the response to therapy and for distinguishing recurrent disease from posttreatment changes. Studies are in progress to evaluate the role of 18FDG-PET imaging in assessing prognosis. In patients who have bronchial carcinoid, somatostatin receptor imaging with 111In-DTPA-pentetreotide (Octreoscan) can help identify patients who are candidates for curative surgery, detect unsuspected metastatic spread, and identify patients who might benefit from certain types of medical therapy. Although it was initially speculated that 18FDG-PET imaging would not be sensitive for tumor detection in patients who have neuroendocrine tumors because of the usual slow metabolism and biology of these tumors, many neuroendocrine tumors are positive on 18FDG-PET imaging. Nevertheless, there has been no direct comparison of 18FDG-PET imaging and somatostatin receptor imaging, nor does a positive or negative 18FDG-PET image exclude neuroendocrine tumor. 18FDG-PET imaging and somatostatin receptor imaging with (99m)Tc-depreotide (Neotect) are safe, cost-effective methods that are valuable in the diagnosis and management of patients who have suspected or known lung cancer. 18FDG-PET and (99m)Tc-depreotide imaging have a high degree of sensitivity, specificity, overall accuracy, and positive and negative predictive values in the evaluation of the solitary pulmonary nodule. These agents provide noninvasive, cost-effective methods for selecting patients for aggressive intervention without contributing to increased morbidity. Both methods have incremental value over CT imaging in selecting patients who have solitary pulmonary nodules for invasive biopsy or for thoracotomy.     

Targeting the epigenome for the treatment of thoracic malignancies

Despite considerable efforts to improve the diagnosis and treatment of lung cancer, this disease remains the leading cause of cancer-related mortality worldwide. Recent elucidation of epigenetic regulation of gene expression during malignant transformation, together with the identification of agents that modulate DNA methylation and histone acetylation, provide new opportunities for the treatment and prevention of lung cancer via chromatin remodeling mechanisms. Further analysis of molecular response in tumor tissues following exposure to chromatin remodeling agents may enable us to identify novel mechanisms pertaining to lung cancer epigenetics, and design more efficacious regimens.     

Complications from induction regimens for thoracic malignancies. Perioperative considerations

The treatment of locoregionally advanced non-small cell lung cancer is evolving rapidly, and we as surgeons should continue to take a prominent role, from the pretreatment evaluation phase, through reassessment after induction therapy and intraoperative decision making, to vigilant postoperative care. These are by far the most challenging thoracic oncologic patients to care for. The multidisciplinary team formula required for optimal results and mandates the leadership that we, as surgeons familiar with all facets of patient care, can provide.     

Follow-up of patients with resected thoracic malignancies

The authors have systematically performed a literature search using 8 databases identifying established guidelines for follow-up after resected thoracic malignancies. Seven different societies' (found to have published recommendations for non-small cell lung cancer, esophageal cancer, thymoma, or mesothelioma) guidelines are reviewed in this article. High-quality evidence leading to consistent, strong recommendations among societies has not been found. With the subsequent advancements in surgical treatment and other curative modalities, the ability to detect and intervene with curative therapy at earlier stages of disease in a growing portion of the current patient population will benefit from higher-quality evidence.     

Minimally invasive open surgery approach for the surgical resection of thoracic malignancies

This article describes minimally invasive open surgery for resection of intrapulmonary malignancies. This approach compensates for the weak points of video-assisted thoracic surgery while remaining minimally invasive. Overall, it is respected as a technically feasible alternative to conventional lobectomy by way of open thoracotomy with an acceptable range of morbidity or mortality.     

Resection of advanced thoracic malignancies requiring cardiopulmonary bypass.

OBJECTIVES: Patients with malignancies involving cardiac structures have limited therapeutic options and significant risk of mortality. The decision to offer radical palliative or curative resection must be made only after consideration of the substantial surgical risks. The purpose of this retrospective study was to determine the feasibility and benefits of resection with cardiopulmonary bypass (CPB) of metastatic or non-cardiac primary malignancies extending directly into or metastasizing to the heart in select patients. Our results were examined to assess the risks and benefits of such radical therapy. METHODS: We retrospectively reviewed patient charts and identified all patients with malignancies involving the cardiac chamber or great vessels (excluding renal carcinomas with caval extension) or with substantial cardiac compression who had undergone resection with CPB at The University of Texas M.D. Anderson Cancer Center between January 1995 and July 2000. We evaluated demographic data, symptomatology, tumor characteristics, and outcomes. RESULTS: Nineteen patients (six males and 13 females; median age of patients, 47 years; age range, 17-67 years) were included in the study. Eleven patients underwent surgery with curative intent, and eight underwent surgery with palliative intent. Seventeen patients had tumors that required CPB because their tumors directly involved the heart and/or great vessels (nine sarcomas, seven epithelial carcinomas, and one unclassified), and two patients (both with sarcomas) required CPB to relieve tumor tamponade. The technique included CPB (n=5), CPB with diastolic arrest (n=12), and CPB with hypothermic circulatory arrest (n=2). Five patients underwent concomitant pneumonectomy, and three underwent lobectomy. Two patients (11%) died in the hospital after resection with palliative intent. Of the 11 patients who underwent resection with curative intent, ten (91%) had complete resections. The median time in the intensive care unit was 5.3 days (range, 0-37 days) and the median length of hospital stay was 17.2 days (range, 0-107 days). Major complications occurred in 11 patients (58%); the most common major complications were pneumonia (n=7 patients), mediastinal hematoma (n=4 patients), and acute respiratory distress syndrome (n=2 patients). The median follow-up duration was 27 months. The overall 1- and 2-year survival rates were 65 and 45%, respectively. CONCLUSIONS: Extensive thoracic tumors involving cardiac structures can be resected with acceptable risk. When resection was performed with curative intent, excellent 1- and 2-year cumulative survival rates were achieved. Although resection with palliative intent was associated with greater mortality rates, some patients survived for 1 and 2 years. The use of CPB in selected patients with thoracic malignancies should be considered, especially when complete resection can be achieved.     

The use of real-time polymerase chain reaction in thoracic malignancies

Recent progress in the molecular analysis of NSCLC tumors and lymph node status will likely translate into a clearer understanding of the variables and predictors of tumor recurrence. This understanding may lead to more appropriate therapeutic decisions both in the operating room and in the clinic. With these analyses at the molecular level, a more precise molecular classification is on the horizon which includes a molecular substaging. All of these aspects of NSCLC biology await testing or final analysis of prospective multi-institutional trials such as that set forth in CALGB 9761.     

Surgical management of thoracic malignancies invading the heart or great vessels

Background

Surgical resection of thoracic malignancies involving either the heart or great vessels is uncommonly performed because of the potential morbidity and mortality for an unknown probability of significant palliation or cure. We reviewed our experience of 10 patients treated surgically, either primarily or as a component of multimodality therapy, to assess feasibility and results.

Methods

A retrospective review of the results in 10 patients who underwent resection of thoracic malignancies that included either great vessel or the heart was conducted.

Results

Histologic diagnoses included soft tissue sarcoma (n = 7), squamous cell carcinoma (n = 1), malignant thymoma (n = 1), and mediastinal teratoma (n = 1). Three patients underwent induction chemotherapy. Cardiopulmonary bypass was used in 7 patients. Structures resected included superior vena cava (n = 5), left atrium (n = 4), right atrium (n = 2), descending aorta (n = 1), and main pulmonary artery (n = 1). Concomitant anatomic pulmonary resections were performed in 3 patients. Seven patients had an R0 or R1 resection. There were no perioperative deaths. All symptomatic patients had immediate and sustained palliation of their presenting symptoms. The median length of stay was 6 days (range, 4 to 43 days). Six patients underwent postoperative systemic therapy. The overall median survival was 21.7 months (range, 3.2 to 69 months) and was 33.3 months (range, 3.7 to 69 months) for patients who had an R0 or R1 resection.

Conclusions

Resection of the heart and great vessels involved by thoracic malignancies can be performed with acceptable morbidity and mortality and results in significant palliation and, in some cases, prolonged survival.     

Immunotherapy for bladder cancer

The primary role of immunotherapy for bladder cancer is to treat superficial transitional cell carcinomas (ie, carcinoma in situ, Ta, and T1). Immunotherapy in the form of bacille Calmette-Guérin (BCG), interferon, bropirimine, keyhole limpet hemocyanin, and gene therapy is intended to treat existing or residual tumor, to prevent recurrence of tumor, to prevent progression of disease, and to prolong survival of patients. Presently, BCG is commonly used and is the most effective immunotherapeutic agent against superficial transitional cell carcinoma. Data support that BCG has a positive impact on tumor recurrence, disease progression, and survival. Proper attention to maintenance schedules, route of administration, dosing, strains, and viability is essential to obtain the maximum benefits of BCG immunotherapy. This review highlights and summarizes the recent advances concerning immunotherapy, with special emphasis on BCG therapy for transitional cell carcinoma.     

Immunotherapy for genitourinary tumors

The present review provides an update about the major achievements and recent advances of immunotherapy in renal cell carcinoma, urothelial carcinoma, and prostate cancer. Although the treatment strategy for renal cell carcinoma and urothelial carcinoma includes traditional cancer immunotherapies, such as interleukin‐2 and interferon‐alfa, the clinical outcomes of these therapies are unsatisfactory. In recent years, the development of immune checkpoint inhibitors has drastically changed the treatment strategy for various cancers, including genitourinary cancer. The present review summarizes the approved cancer immunotherapies for renal cell carcinoma, urothelial carcinoma and prostate cancer. Furthermore, we review the response evaluation and biomarkers for immune checkpoint inhibitors with a distinctive mode of action that is different from cytotoxic agents. Finally, future perspectives for cancer immunotherapy are discussed.