Treatment Of Primary Lung Cancer Research Articles

Examining patient burden and drivers of delayed care in patients undergoing surgical treatment of primary lung cancer.

153 Background: Patients’ geographic location can impact access to specialty care and affect the appropriateness and timeliness of evaluation leading to primary surgical treatment of lung cancer. Cancer care coordination has long been speculated to lead to greater efficiency in oncologic care, yet objective measures demonstrating the utility of such healthcare team members is lacking. We aimed to study the impact of patients’ residence on healthcare encounters, travel burden and the distribution of physiologic and oncologic workup leading to delays in care at a specialty cancer center. Methods: We conducted a single center retrospective cohort study of 103 patients undergoing workup of primary lung cancer between January 2015 and August 2017. The shortest route between patient residence and treating medical center was measured in miles and classified as: urban ( < 40 miles); rural (40.1 – 100 miles); and regional (100.1 – 1,000 miles). Average total miles traveled (i.e. travel burden), total number of healthcare encounters, and the distribution of physiologic and oncologic evaluations as drivers of delay in care were examined. Results: Patients were categorized as urban n = 80 (77.7%); rural n = 12 (11.7%); and regional n = 11 (10.7%). Median travel burden (urban = 100 miles [interquartile range, IQR 56-216.8]; rural = 385.7 [127.1 – 769]; regional = 780 [560 – 1936]; p < 0.001) and median total healthcare encounters (urban = 7 [6-9]; rural = 9 [7-9.5]; regional = 10 [7-12]; p = 0.3) increased with greater distance of patient residence from treating medical center. Additional necessary physiologic workup was associated with delayed care and greater burden in the rural and regional patients compared to those residing in urban locations (urban = 21% increase; rural = 152%; regional = 162%). Additional oncologic workup was associated with delayed care in the regional group only (49% increase). These trends remained even when controlling for clinical stage. Conclusions: These findings demonstrate the need for better cancer care coordination for rural and regional lung cancer patients to improve efficiency, appropriateness and timeliness of care while decreasing patient-related burdens.

Result of the 6-min walk test is an independent prognostic factor of surgically treated non-small-cell lung cancer.

Pathological tumour, node and metastasis (TNM) stage remains the most significant prognostic factor of non-small-cell lung cancer (NSCLC). Meanwhile, age, gender, pulmonary function tests, the extent of surgical resection and the presence of concomitant diseases are commonly used to complete the prognostic profile of the patient with early stage of NSCLC. The aim of this study is to assess how the result of a 6-min walk test (6MWT) further assists in predicting the prognosis of NSCLC surgical candidates. Six hundred and twenty-four patients who underwent surgical treatment for NSCLC between April 2009 and October 2011 were enrolled in this study. All patients were accepted for surgery on the basis of a standard evaluation protocol. Additionally, patients completed the 6MWT on the day before the surgery, and threshold values of the test were assessed based on both the Akaike information criterion and the coefficient of determination R2. Cox proportional hazards regression analysis was used to analyse the effect of important prognostic factors on the overall survival. Three hundred and ninety men and 234 women with a mean age of 64 years underwent radical surgical treatment for primary lung cancer. Five hundred and twenty-five lobectomies (84%), 77 pneumonectomies (12%) and 24 (4%) lesser resections were performed. Three hundred and thirty-one patients (53%) were treated for stage I NSCLC, 191 patients (31%) for stage II and 102 patients (16%) for stages IIIA-IV. A distance of 525 m in the 6MWT [hazard ratio (HR) = 0.57, 95% confidence interval (CI) 0.41-0.78, P < 0.001] was the threshold value differentiating the patients' prognoses (P < 0.001). Using the Cox proportional hazards regression analysis, pathological TNM stage (IIA: HR = 1.87, 95% CI 1.95-2.92, P = 0.006; IIB: HR = 2.03, 95% CI 1.23-3.37, P = 0.006; IIIA-IV: HR = 2.37, 95% CI 1.49-3.75, P < 0.001), male gender (HR = 1.88, 95% CI 1.26-2.79, P = 0.001), pneumonectomy (HR = 1.78, 95% CI 1.17-2.70, P < 0.001) and the results of the 6MWT (HR = 0.50, 95% CI 0.36-0.70, P < 0.001) were considered as independent predictive factors of overall survival. The result of a 6MWT is an independent and convenient prognostic factor of surgically treated non-small-cell lung cancer.

Abstract 4376: Tumor treating fields (TTFields) decrease proliferation of patient-derived lung cancer brain metastasis cells in vitro

Abstract Up to 40% of all non-small cell lung cancer (NSCLC) patients will develop brain metastases during the course of their disease, with ~20-25% of patients presenting with brain metastases at the time of their initial lung cancer diagnosis. For the latter patient population, median survival is a dismal 8 months. Systemic therapies are typically ineffective at treating the brain metastases, even in cases when the extracranial disease responds to the therapy. Clinical trials utilizing TTFields therapy in patients with lung cancer brain metastases are underway. For these trials, TTFields are delivered at 150 kHz, as that is the frequency that has been determined for the treatment of primary lung cancer. In contrast, for the FDA-approved treatment of the most common malignant primary brain tumor, glioblastoma, TTFields are delivered at 200 kHz. Therefore, in this study, a patient-derived lung cancer brain metastatic cell line was assessed to compare the response to in vitro TTFields application at either 150 or 200 kHz compared to untreated control cells. Methods: Use of patient tumor tissue for this study was approved by the Wayne State University Institutional Review Board and written informed consent was obtained from the patient. An adenocarcinoma lung cancer brain metastasis (from a patient that presented with the brain metastasis at the time of diagnosis) was collected immediately following microsurgical resection. A single-cell suspension from the tumor tissue was prepared by enzymatic and mechanical disruption. After 7 passages in vitro, cells were plated on plastic coverslips (10,000 each) in DMEM/F12 media supplemented with 10% fetal bovine serum. TTFields were applied at ~1.6 V/cm at 150 or 200 kHz (groups n=4-5) with one control group. Culture media was replaced every day. After 10 days of in vitro TTFields application, cell proliferation was assessed with the XTT assay. Control vs. TTFields-treated groups were compared with two-tailed t-tests. Results: The 10-day TTFields treatment resulted in significantly reduced cellular proliferation in the cells that received 150 kHz TTFields (0.220±0.006; mean±SEM) compared to the control cells (0.250±0.009; p=0.0237) with no statistical difference between the control and the cells that received 200 kHz TTFields (0.230±0.008; p&amp;gt;0.05). Conclusions: Application of TTFields in vitro at 150 kHz reduced cellular proliferation in patient-derived lung cancer brain metastasis cells, with no reduction of proliferation after application of TTFields at 200 kHz. This is the first report on the in vitro effects of TTFields in a patient-derived NSCLC brain metastasis cell line. Citation Format: Sharon K. Michelhaugh, Sam Kiousis, Neil V. Klinger, Sandeep Mittal. Tumor treating fields (TTFields) decrease proliferation of patient-derived lung cancer brain metastasis cells in vitro [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4376.

Inhalation treatment of primary lung cancer using liposomal curcumin dry powder inhalers

Lung cancer is the leading cause of cancer-related deaths. Traditional chemotherapy causes serious toxicity due to the wide bodily distribution of these drugs. Curcumin is a potential anticancer agent but its low water solubility, poor bioavailability and rapid metabolism significantly limits clinical applications. Here we developed a liposomal curcumin dry powder inhaler (LCD) for inhalation treatment of primary lung cancer. LCDs were obtained from curcumin liposomes after freeze-drying. The LCDs had a mass mean aerodynamic diameter of 5.81 μm and a fine particle fraction of 46.71%, suitable for pulmonary delivery. The uptake of curcumin liposomes by human lung cancer A549 cells was markedly greater and faster than that of free curcumin. The high cytotoxicity on A549 cells and the low cytotoxicity of curcumin liposomes on normal human bronchial BEAS-2B epithelial cells yielded a high selection index partly due to increased cell apoptosis. Curcumin powders, LCDs and gemcitabine were directly sprayed into the lungs of rats with lung cancer through the trachea. LCDs showed higher anticancer effects than the other two medications with regard to pathology and the expression of many cancer-related markers including VEGF, malondialdehyde, TNF-α, caspase-3 and BCL-2. LCDs are a promising medication for inhalation treatment of lung cancer with high therapeutic efficiency.

Diagnosis and Treatment for Multiple Primary Lung Cancer

Diagnosis and Treatment for Multiple Primary Lung Cancer

急性膿胸を合併した原発性肺癌の 1 切除例

急性膿胸を合併した原発性肺癌の 1 切除例

Video-Assisted Thoracoscopic Lobectomy for Lung Cancer: Current Practice Patterns and Predictors of Adoption

Video-assisted thoracoscopic surgery (VATS) lobectomy has been shown to be a safe, minimally invasive approach for the surgical management of lung cancer. Despite evidence supporting oncologic efficacy, recent reports indicate that less than half of lobectomies are performed by VATS. We examined nationwide lobectomy practice patterns to identify specific predictors for VATS adoption. Premier hospital data (2010 to 2014) were used to identify open and VATS lobectomy procedures performed for the treatment of primary lung cancer. Propensity score method was used to match VATS and open operations (1:1) on clinical characteristics. Variables associated with VATS lobectomy were assessed by logistic regression to evaluate independent predictors. Secondary outcomes included postoperative complications, readmission, and mortality. Patients with primary lung cancer (n= 17,304) that underwent VATS (n= 6,670, 38.5%) or open (n= 10,634, 61.5%) lobectomy were identified; 6,670 patients in each group were matched for analysis. VATS performance increased significantly from 2010 to 2014, (39.6% versus 43.8%, p= 0.0004), particularly for thoracic surgeons (50.3% versus 54.7%, p < 0.0001), those performing 15 or more lobectomies per year (53.6% versus 59.8%, p<0.0001), and for surgeons practicing in the Northeast (54.8% versus 59.9%, p= 0.0001). Independent predictors of VATS utilization included surgeon volume and specialty training, hospital type and size, and region. Multivariate analysis demonstrated a significant association between VATS and surgeon volume, independent of specialty. National rates of VATS lobectomy continue to increase, particularly for thoracic surgeons, high-volume surgeons, and surgeons in the Northeast. Surgeon volume and specialty are strong independent predictors of VATS lobectomy. Efforts that support centralization of care may improve VATS lobectomy rates and decrease the regional variability identified in this analysis.

Pulmonary imaging after stereotactic radiotherapy-does RECIST still apply?

The use of stereotactic ablative radiotherapy (SABR) for the treatment of primary lung cancer and metastatic disease is rapidly increasing. However, the presence of benign fibrotic changes on CT imaging makes response assessment following SABR a challenge, as these changes develop with an appearance similar to tumour recurrence. Misclassification of benign fibrosis as local recurrence has resulted in unnecessary interventions, including biopsy and surgical resection. Response evaluation criteria in solid tumours (RECIST) are widely used as a universal set of guidelines to assess tumour response following treatment. However, in the context of non-spherical and irregular post-SABR fibrotic changes, the RECIST criteria can have several limitations. Positron emission tomography can also play a role in response assessment following SABR; however, false-positive results in regions of inflammatory lung post-SABR can be a major clinical issue and optimal standardized uptake values to distinguish fibrosis and recurrence have not been determined. Although validated CT high-risk features show a high sensitivity and specificity for predicting recurrence, most recurrences are not detected until more than 1-year post-treatment. Advanced quantitative radiomic analysis on CT imaging has demonstrated promise in distinguishing benign fibrotic changes from local recurrence at earlier time points, and more accurately, than physician assessment. Overall, the use of RECIST alone may prove inferior to novel metrics of assessing response.

Chinese guidelines on the diagnosis and treatment of primary lung cancer (2015 version).

These guidelines update the Chinese Guidelines on the Diagnosis and Treatment of Primary Lung Cancer (2011 Version) released by the former Ministry of Health of the People's Republic of China. The purpose of this work is to standardize the diagnosis and treatment protocols of primary lung cancer and enhance the related practice at medical institutions in order to improve the prognosis of patients with primary lung cancer and the quality and safety of health care services.

Results of surgical treatment of primary lung cancer with synchronous brain metastases.

IntroductionThe surgical treatment of non-small cell lung cancer (NSCLC) with synchronous brain matastases is more effective than other therapeutic options, but this management is still controversial.The aim of the studyThe aim of the study was to evaluate the survival of patients after pulmonary resection NSCLC preceded by resection of brain metastases.Material and methodsFrom 2007 to 2012, 645 patients underwent pulmonary resection for NSCLC at our department. In 25 of them (3.87%) thoracic surgery was preceded by resection of a single brain metastasis of NSCLC and a PET CT scan. No signs of nodal involvement or distant metastases were detected.ResultsThe group consisted of 18 men (72%) and 7 women (28%). Average age was 57.62 years (46-70). In all cases, whole brain radiotherapy (5 × 4 Gy) was performed. The average interval between excision of brain metastasis and lung resection was 31.4 days (27-41). Pneumonectomy was performed in 1, lobectomy/bilobectomy in 17 and wedge resection in 7 cases. Pathological stage N0 was diagnosed in 17, N1 in 5 and N2 in 3 patients. Average survival was 18.68 months (4-74). Survival at 1, 2 and 5 years was 64%, 28% and 28% respectively. Average disease-free survival was 17.52 months. Histological type (p = 0.57) and G (p = 0.82) have no influence on survival. All the patients with hilar lymph node involvement died within 26 months and with mediastinal one within 12 months.ConclusionsSurgical treatment of patients with NSCLC with synchronous brain metastases may prove beneficial in selected patients after excluding other distant metastases and lymph node involvement.

Co-treatment with therapeutic neural stem cells expressing carboxyl esterase and CPT-11 inhibit growth of primary and metastatic lung cancers in mice.

In this study, neural stem cells (NSCs)-derived enzyme/prodrug therapy (NDEPT) was used to treat primary lung cancer or metastatic lung cancer in the brain. To confirm the anti-tumor effect of NSCs expressing carboxyl esterase (CE), A549 lung cancer cells were treated with HB1.F3.CE cells and CPT-11. A significant decrease in the viability/proliferation of lung cancer cells was observed compared to negative controls or cells treated with CPT-11 alone. To produce a mouse model of primary lung cancer or lung cancer metastasis to the brain, A549 cells were implanted in the dorsal area of the mouse or right hemisphere. CM-DiI pre-stained stem cells were implanted near the primary lung cancer tumor mass or in the contralateral brain. Two days after stem cells injection, mice were inoculated with CPT-11 (13.5 kg/mouse/day) via intraperitoneal injection. In the primary lung cancer mouse models, tumor mass was 80% lower in response to HB1.F3.CE in conjunction with CPT-11, while it was only reduced by 40% in the group treated with CPT-11 alone. Additionally, therapeutic efficacy of co-treatment with stem cells and CPT-11 was confirmed by detection of apoptosis and necrosis in primary and metastatic lung cancer tissues. By secreting VEGF, tumor cells modulate Erk1/2 and Akt signaling and migration of stem cells. This further increased tumor-selectivity of stem cell/prodrug co-therapy. Overall, these results indicate that NSCs expressing the therapeutic gene may be a powerful tool for treatment of primary lung cancer or metastasis of lung cancer to the brain.

Pulmonary metastasectomy by VATS or open thoractomy: a systematic review and meta-analysis of long term outcomes

Background VATS has become an increasingly popular technique for the cardiothoracic surgeon. Its use in the treatment of malignancy has been an issue of debate previously. Whilst its use has been documented for the treatment of primary lung cancers, its use in metastasectomy has been questioned due to inability to palpate the lung (with the possibility of missing lesions not diagnosed by low sensitivity pre-operative CT) and the association with pleural and port site seeding. There remain no randomized trials and other high level evidence regarding the oncological outcomes of VATS versus open thoracotomy for pulmonary metastases.

Metachronous lung cancer that presented as bilateral synchronous lung cancer.

Every patient undergoing curative treatment for primary lung cancer is a candidate for metachronous lung cancer, with a reported risk of 5% per year. The majority of cases are stage I patients. Patients who undergo resection for lung cancer should be followed regularly. A metachronous lung cancer that develops as bilateral synchronous lung cancer is very rare.

Chinese guidelines on the diagnosis and treatment of primary lung cancer (2011 version)

Chinese guidelines on the diagnosis and treatment of primary lung cancer (2011 version)

Surgical treatment for primary lung cancer combined with idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause. IPF is associated with an increased risk of lung cancer, and lung cancer patients with IPF undergoing pulmonary resection for non-small cell lung cancer have increased postoperative morbidity and mortality. Especially, postoperative acute exacerbation of IPF (AEIPF) causes fatal status and long-term outcomes are worse than for patients without IPF, although certain subgroups have a good long-term outcome. A comprehensive review of the current literature pertaining to AEIPF and the late phase outcome after the context of a surgical intervention was performed.

Clinical pathway for surgical treatment of primary lung cancer (2012 Edition).

Diagnosis is based on the “Diagnosis and Treatment Practices for Primary Lung Cancer (2011)” and the “Diagnosis Practices for Primary Lung Cancer (2011)” released by the Ministry of Health of China

Adjuvant chemotherapy for surgically resected non–small cell lung cancer

Despite surgical resection, patients with early-stage (I to IIIA) non-small cell lung cancer (NSCLC) are at considerable risk of recurrence and death from their lung cancer. In recent years, multiple, large, randomized trials assessing the efficacy of adjuvant chemotherapy for resected NSCLC have been reported. Three of 6 trials with 300 or more patients with early-stage NSCLC have demonstrated that adjuvant cisplatin-based chemotherapy can significantly improve 5-year survival in carefully selected patients with resected NSCLC. These benefits have been confirmed in a meta-analysis of modern cisplatin-based adjuvant trials. The most consistent benefit has been reported in patients with resected stage II and IIIA NSCLC. The benefit of adjuvant chemotherapy in patients with resected stage IB NSCLC is less concrete. Herein, we review the results of the major adjuvant chemotherapy trials and their implications for the treatment of patients with completely resected NSCLC. A future challenge will be to identify the subsets of patients who will derive the greatest benefit from adjuvant chemotherapy. Current trials are also underway to define the role of novel targeted therapies, such as inhibitors of the epidermal growth factor receptor and monoclonal antibodies, in adjuvant treatment strategies.

Treatment of Lung Metastases from Ewing Sarcoma with Stereotactic Body Radiotherapy rather than Whole-Lung Irradiation

ABSTRACT Advances in knowledge Lung metastases from Ewing sarcoma have traditionally been treated with whole-lung irradiation (WLI) and chemotherapy. WLI may unnecessarily treat uninvolved normal lung tissue and increase the risk of toxicity. Stereotactic body radiotherapy (SBRT) has proven to be a safe and effective treatment for primary lung cancer and lung metastases, but there is no significant published description of SBRT in lung metastases from Ewing sarcoma. Implications for patient care The patient presented in this case report had long-term survival from lung metastases of Ewing sarcoma treated with chemotherapy and SBRT. SBRT may prove to be safer and more effective than whole lung irradiation as a treatment of lung metastases in Ewing sarcoma. Summary statement Whether SBRT of lung metastases of Ewing sarcoma can improve outcomes and decrease toxicity compared to whole-lung irradiation, surgical resection or palliative chemotherapy merits further study. How to cite this article Rahn DA, Read W, Sandhu A. Treatment of Lung Metastases from Ewing Sarcoma with Stereotactic Body Radiotherapy rather than Whole-Lung Irradiation. J Postgrad Med Edu Res 2012;46(1):34-36.

A Case of Lung Squamous Cell Carcinoma Mimicking Benign Solitary Cyst

Lung cancer with cyst formation is a rare entity. We report a 63-year-old man who underwent surgical treatment of primary lung cancer, which mimics benign solitary cyst. We incidentally found his pulmonary cyst by a low dose chest tomography and followed up for 2 years. Rapid growth of cyst and focal wall thickening evoke us to have a suspicion of its malignancy. Left lower lobectomy via video-assisted thoracoscopic surgery was performed without any preoperative pathologic confirmation. The postoperative pathological finding revealed squamous cell carcinoma with carcinoma in situ on the cyst wall. We emphasize the need for physicians to be aware of the potential of lung cancer in patients with growing pulmonary cyst. (J Lung Cancer 2012;11(2):108�� 110)

Polymerase Chain Reaction Positivity of Pneumocystis Jirovecii during Primary Lung Cancer Treatment

Polymerase Chain Reaction Positivity of <i>Pneumocystis Jirovecii</i> during Primary Lung Cancer Treatment