Porfimer Sodium Versus PS785 for Photodynamic Therapy (PDT) of Lung Cancer Xenografts in Mice.

BACKGROUND: Lung cancer is the greatest cause of cancer mortality in the United States, necessitating ongoing improvements in current treatment techniques. Photodynamic therapy (PDT) involves the interaction between a photosensitizer, light, and oxygen. The resulting release of reactive oxygen species causes tumor necrosis. It has been used as an endoscopic technique for the palliation of lung cancer. Porfimer sodium (Photofrin) is the only Food and Drug Administration-approved photosensitizer for PDT but has limited depth of penetration and produces prolonged skin phototoxicity. Multiple newer photosensitizers are in development, including PS785. The effectiveness of PS785 was compared with porfimer sodium in the treatment of human lung cancer xenografts in mice. METHODS: Human non-small cell lung cancer (NSCLC) xenografts were established in severe combined immunodeficient mice and grouped into small (3-5 mm) and large tumors (6-10 mm). PS785 or porfimer sodium was administered intravenously, and PDT was executed at 24, 48, or 72 h after injection. The primary endpoint was the delay of tumor regrowth after PDT. RESULTS: Porfimer sodium and PS785 produced statistically similar delays of tumor regrowth after PDT when small tumors were treated at 24 and 48 h. At 72 h, PS785 performed better in small tumors. However, for large tumors, PS785 produced no delay in tumor regrowth at any time point. CONCLUSIONS: PS785 and porfimer sodium were able to effectively treat NSCLC to a depth of ≤5 mm. However, porfimer sodium was more effective in treating NSCLC tumors to a depth of 6-10 mm. Further efforts are required to produce photosensitizers that will facilitate PDT of larger tumors.

An Optical Surface Applicator for Intraoperative Photodynamic Therapy.

BACKGROUND AND OBJECTIVES: Intraoperative photodynamic therapy (IO-PDT) is typically administered by a handheld light source. This can result in uncontrolled distribution of light irradiance that impacts tissue and tumor response to photodynamic therapy. The objective of this work was to characterize a novel optical surface applicator (OSA) designed to administer controlled light irradiance in IO-PDT. STUDY DESIGN/MATERIALS AND METHODS: An OSA was constructed from a flexible silicone mesh applicator with multiple cylindrically diffusing optical fibers (CDF) placed into channels of the silicone. Light irradiance distribution, at 665 nm, was evaluated on the OSA surface and after passage through solid tissue-mimicking optical phantoms by measurements from a multi-channel dosimetry system. As a proof of concept, the light administration of the OSA was tested in a pilot study by conducting a feasibility and performance test with 665-nm laser light to activate 2-(1'-hexyloxyethyl) pyropheophorbide-a (HPPH) in the thoracic cavity of adult swine. RESULTS: At the OSA surface, the irradiance distribution was non-uniform, ranging from 128 to 346 mW/cm2 . However, in the tissue-mimicking phantoms, beam uniformity improved markedly, with irradiance ranges of 39-153, 33-87, and 12-28 mW/cm2 measured at phantom thicknesses of 3, 5, and 10 mm, respectively. The OSA safely delivered the prescribed light dose to the thoracic cavities of four swine. CONCLUSIONS: The OSA can provide predictable light irradiances for administering a well-defined and potentially effective therapeutic light in IO-PDT. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Cancer Registration in Resource-limited Environments-Experience in Lagos, Nigeria.

BACKGROUND: Cancer registration provides data that can be utilized to study the etiology, diagnosis, prevention, and treatment of cancer. Despite the efforts of the World Health Organization (WHO), cancer registration is still underdeveloped in low- and middle-income countries (LMICs). This is the case in Lagos, Nigeria. Lakeshore Cancer Center (LCC) sought to retrospectively collect and describe the characteristics of the patients seen in its first 2 y of existence. METHODS: A retrospective review of patient records presenting at LCC was performed. Various parameters were collected such as demographics and diagnoses. These data were used to perform a simple descriptive analysis. A series of consultations determined what parameters to include in the registry. CanReg, a cancer registration application, was customized to include these parameters. RESULTS: Between July 2014 and June 2016, a total of 226 cancer incidence cases were presented at LCC. There was an increasing number of new cancer cases when evaluated at 6-mo intervals. The most common cancers presented were breast (38%), prostate (12%), and colorectal (8%) cancers. The majority of patients (85%) were presented at later cancer stages. CONCLUSIONS: Breast, prostate, and colorectal cancers were the three most common cancer cases seen at LCC. Late-stage presentation remains a challenge. These results reveal the need for early detection and screening methods to help change the stage distribution. The cancer registry will be utilized to collect cancer data and to allow for analysis and better treatment/prevention protocols. Collaboration with other academic centers in the region will facilitate the establishment of a population-based registry.

Concomitant Mediastinoscopy Increases the Risk of Postoperative Pneumonia After Pulmonary Lobectomy.

BACKGROUND: Mediastinoscopy is considered the gold standard for preresectional staging of lung cancer. We sought to examine the effect of concomitant mediastinoscopy on postoperative pneumonia (POP) in patients undergoing lobectomy. METHODS: All patients in our institutional database (2008-2015) undergoing lobectomy who did not receive neoadjuvant therapy were included in our study. The relationship between mediastinoscopy and POP was examined using univariate (Chi square) and multivariate analyses (binary logistic regression). In order to validate our institutional findings, lobectomy data in the National Surgical Quality Improvement Program (NSQIP) from 2005 to 2014 were analyzed for these associations. RESULTS: Of 810 patients who underwent a lobectomy at our institution, 741 (91.5%) surgeries were performed by video-assisted thoracic surgery (VATS) and 487 (60.1%) patients underwent concomitant mediastinoscopy. Univariate analysis demonstrated an association between mediastinoscopy and POP in patients undergoing VATS [odds ratio (OR) 1.80; p = 0.003], but not open lobectomy. Multivariate analysis retained mediastinoscopy as a variable, although the relationship showed only a trend (OR 1.64; p = 0.1). In the NSQIP cohort (N = 12,562), concomitant mediastinoscopy was performed in 9.0% of patients, with 44.5% of all the lobectomies performed by VATS. Mediastinoscopy was associated with POP in patients having both open (OR1.69; p < 0.001) and VATS lobectomy (OR 1.72; p = 0.002). This effect remained in multivariate analysis in both the open and VATS lobectomy groups (OR 1.46, p = 0.003; and 1.53, p = 0.02, respectively). CONCLUSIONS: Mediastinoscopy may be associated with an increased risk of POP after pulmonary lobectomy. This observation should be examined in other datasets as it potentially impacts preresectional staging algorithms for patients with lung cancer.

Photodynamic therapy of human lung cancer xenografts in mice.

BACKGROUND: There is a need to develop novel therapies for non-small cell lung cancer (NSCLC). Photodynamic therapy has been used successfully for endobronchial palliation of NSCLC, and its role in early stages of disease is being explored. We hypothesized that a novel photosensitizer, PS1, would be more effective than the standard agent, porfimer sodium (Photofrin or PFII), in treating human lung cancer xenografts in mice. MATERIALS AND METHODS: Patient-derived NSCLC xenografts were established subcutaneously in severe combined immune deficiency mice. Two groups of five mice were injected with PS1 (3-[1'-m-iodobenzyloxy]ethyl-3-devinylpyropheophorbide-a), a chlorophyll-a derivative, or PFII (a purified version of hematoporphyrin derivative) and then treated with nonthermal laser light. Four mice were treated with laser light without photosensitizer and six mice received no treatment at all. All mice were then observed for tumor growth. The tumor growth end point, time-to-1000 mm(3), was evaluated using standard Kaplan-Meier methods and the log-rank test. Tumor hematoxylin and eosin and caspase 3 staining was done to evaluate necrosis and apoptosis. RESULTS: The median time-to-1000 mm(3) was 12, 12, 26, and 52 d for the control, light only, PFII, and PS1 groups. There was a significant association between the tumor growth end point and treatment (P < 0.05). Hematoxylin and eosin staining revealed <1%, 0%, 67%, and 80% necrosis, and caspase 3 positivity was 2%, <1%, 17%, and 39%, respectively, in the same four groups. CONCLUSIONS: The mice treated with PS1 exhibited a longer time for tumor regrowth and showed more tumor necrosis and apoptosis compared with the other treatment groups. Thus, the novel photosensitizer, PS1, was demonstrated to be more effective than porfimer sodium in this preclinical pilot study.

Automated tobacco assessment and cessation support for cancer patients.

BACKGROUND: Tobacco assessment and cessation support are not routinely included in cancer care. An automated tobacco assessment and cessation program was developed to increase the delivery of tobacco cessation support for cancer patients. METHODS: A structured tobacco assessment was incorporated into the electronic health record at Roswell Park Cancer Institute to identify tobacco use in cancer patients at diagnosis and during follow-up. All patients who reported tobacco use within the past 30 days were automatically referred to a dedicated cessation program that provided cessation counseling. Data were analyzed for referral accuracy and interest in cessation support. RESULTS: Between October 2010 and December 2012, 11,868 patients were screened for tobacco use, and 2765 were identified as tobacco users and were referred to the cessation service. In referred patients, 1381 of those patients received only a mailed invitation to contact the cessation service, and 1384 received a mailing as well as telephone contact attempts from the cessation service. In the 1126 (81.4%) patients contacted by telephone, 51 (4.5%) reported no tobacco use within the past 30 days, 35 (3.1%) were medically unable to participate, and 30 (2.7%) declined participation. Of the 1381 patients who received only a mailed invitation, 16 (1.2%) contacted the cessation program for assistance. Three questions at initial consult and follow-up generated over 98% of referrals. Tobacco assessment frequency every 4 weeks delayed referral in < 1% of patients. CONCLUSIONS: An automated electronic health record-based tobacco assessment and cessation referral program can identify substantial numbers of smokers who are receptive to enrollment in a cessation support service.

Prognostic implications of signet ring cell histology in esophageal adenocarcinoma.

BACKGROUND: Signet ring cell esophageal adenocarcinoma histology has been difficult to study in single institution series because of its relative rarity, yet has an anecdotal reputation for poor prognosis. The Surveillance, Epidemiology, and End Results (SEER) database was examined to assess the prognostic implications of this esophageal adenocarcinoma subtype. METHODS: All patients with esophageal adenocarcinoma in the SEER database from 2004 to 2009 were included. Univariate and multivariate analyses examining the relationship of signet ring cell histology with overall survival were performed in all patients, as well as those undergoing surgical resection. RESULTS: A total of 596 of 11,825 (5%) study patients had signet ring cell histology. Patients with signet ring cell histology were similar in age, race, and sex distribution, but had a higher grade (P < .001) and higher stage (P < .001) at diagnosis. In both the all-patient group as well as those undergoing surgical resection, univariate analyses showed a worse survival in patients with signet ring cell esophageal cancer (hazard ratio [HR] = 1.24; 95% confidence interval [CI] = 1.13-1.36 and HR = 1.57; 95% CI = 1.29-1.93, respectively). In multivariate analyses adjusting for covariates, patients with signet ring cell cancer had a worse prognosis than those without (HR = 1.18; 95% CI = 1.07-1.30). In surgically resected patients, this remained a trend, but did not reach statistical significance (HR = 1.16; 95% CI = 0.94-1.42). CONCLUSIONS: This large study of esophageal adenocarcinoma confirms the clinical impression that signet ring cell variant of adenocarcinoma is associated with an advanced stage at presentation and a worse prognosis independent of stage of presentation.

Small cell carcinoma of the esophagus: a SEER database analysis.

BACKGROUND: Small cell cancer (SCC) of the esophagus is an uncommon malignancy with perceived poor prognosis, but there are few data to guide therapeutic decisions. We examined the Surveillance, Epidemiology, and End Results (SEER) database to identify prognostic factors for survival. METHODS: All patients with esophageal cancer in the SEER database between 1973 and 2009 were included. Univariate and multivariate analyses were performed in patients with and without SCC, examining the relationship of small cell histology, surgery, and other potential prognostic factors with overall survival (censored at 72 months). RESULTS: Of 64,799 esophageal cancer patients identified in the SEER database, 387 (0.6 %) had small cell histology. As compared with non-small cell histology, patients with small cell histology were similar in age and race but had a higher proportion of women (p < 0.001), had a higher stage at diagnosis (p < 0.001), and were less likely to undergo surgical resection (p < 0.01). Multivariate predictors associated with poor survival in the overall cohort included age, female gender, black race, and stage. In patients treated with surgery, multivariate predictors associated with poor survival included age, male gender, race, and stage but not small cell histology. In patients with small cell histology, both age and stage were associated with poor survival, but surgery and preoperative radiotherapy were associated with improved survival. CONCLUSIONS: SCC of the esophagus presents at an advanced stage and confers a poor prognosis. The survival benefit of surgery and radiotherapy suggests that all esophageal SCC patients should be considered for preoperative radiotherapy and surgery in a stage-appropriate fashion.

Temporal trends in outcomes following sublobar and lobar resections for small (≤ 2 cm) non-small cell lung cancers--a Surveillance Epidemiology End Results database analysis.

BACKGROUND: Since the randomized, controlled study that favored lobectomy for resection of stage I non-small cell lung cancers (NSCLCs) by the Lung Cancer Study Group, there have been improvements in staging. The liberal use of computed tomography also may have altered the types of early lung cancer diagnosed. Studies published since then have drawn contradictory conclusions on the benefit of lobectomy over sublobar resections for early-stage NSCLC. We examined the Surveillance Epidemiology End Results database to test our hypothesis that the relationship between extent of resection and outcome has changed since the Lung Cancer Study Group study was published. METHODS: We examined stage I NSCLCs ≤ 2 cm in size over three periods: 1988-1998 (Early), 1999-2004 (Intermediate), and 2005-2008 (Late). For each period, we assessed overall and disease-specific survivals and their associations with the extents of resection, by univariate and multivariate analyses. Sublobar resections in the Early group could not be categorized into segmentectomies and wedge resections because these were not coded separately. RESULTS: The proportion of NSCLCs ≤ 2 cm increased from 0.98% in 1988 to 2.2% in 2008. Multivariate analyses showed that sublobar resection was inferior to lobectomy in the Early period (hazard ratio [HR], 1.41; 95% confidence interval [CI], 1.21-1.65). This effect decreased in the Intermediate period, in which segmentectomies but not wedge resections were equivalent to lobectomies (wedge versus lobectomy HR, 1.19; 95% CI, 1.01-1.41; segmentectomy versus lobectomy HR, 1.04; 95% CI, 0.8-1.36). The difference disappeared in the Late period, when both wedge resections and segmentectomies were equivalent to lobectomy (wedge versus lobectomy HR, 1.09; 95% CI, 0.79-1.5; segmentectomy versus lobectomy HR, 0.83; 95% CI, 0.47-1.45). Trends for both overall survival and disease-specific survival were identical. CONCLUSIONS: The survival benefit of lobectomy over sublobar resection decreased over the past 2 decades with no discernible difference in the most contemporary cases. These results support reevaluation of lobectomy as the standard of care for small (≤ 2-cm) NSCLCs.

Using an Adapted Tumor Board Evaluation Tool for Quality Assessment of a Thoracic Multidisciplinary Cancer Conference: A Pilot Study.

PURPOSE: Multidisciplinary cancer conferences (MCCs) are crucial for the management of complex oncology patients. Tools to evaluate MCC performance are needed. The aim of this pilot study was to assess the applicability of an existing validated performance assessment tool to evaluate the quality of thoracic MCCs (T-MCCs). METHODS: Data were collected from weekly T-MCCs over a 5-week period using the MCC Performance Assessment Tool and a self-assessment survey. Audio recordings were used to supplement observation notes. Case presentation, discussion duration, decision making contribution, recommendations, and consensus were captured. Quality of information and contribution were rated on a 1-5 scale. The data were analyzed using descriptive statistics to calculate means and composite scores representing overall MCC performance. RESULTS: A total of 44 cases were observed at the T-MCC with the mean presentation and discussion time of 6 minutes and 22 seconds. Quality of case history, radiologic and pathological information, and reason for case discussion were rated above average (>3), whereas inclusion of comorbidities and patient views were rated below average. Surgical oncologists had a higher discussion contribution compared with medical and radiation oncologists (3.6 v 2.9 and 2.4, respectively). The overall mean composite score was 55.9 (deemed average) with no cases categorized as poor or excellent. Radiologists and pathologists had mean preparation times of 81.7 and 144.0 minutes, respectively. CONCLUSION: This study demonstrated the applicability of a previously validated tool to assess the quality of a T-MCC at an academic comprehensive cancer center. The tool was found to be useful in identifying elements of the T-MCC process that needed improvement.

Analyzing the impact of minimally invasive surgical approaches on post-operative outcomes of pneumonectomy and sleeve lobectomy patients.

Background: Some patients with non-small cell lung cancer (NSCLC) have superior short- and long-term outcomes with sleeve lobectomy rather than pneumonectomy. Originally sleeve lobectomy was reserved for patients with limited pulmonary function, however, the reported superior results allowed sleeve lobectomy to be performed in expanded patient populations. In a further attempt to improve post-operative outcomes surgeons have adopted minimally invasive techniques Minimally invasive approaches have potential benefits to patients such as decreased morbidity and mortality while maintaining the same caliber of oncologic outcomes. Methods: We identified patients at our institution who underwent sleeve lobectomy or pneumonectomy to treat NSCLC from 2007 to 2017. We analyzed these groups in respect to 30- and 90-day mortality, complications, local recurrence, and median survival. We included multivariate analysis to determine the impact of a minimally invasive approach, sex, extent of resection, and histology. Differences in mortality were analyzed using the Kaplan-Meier method using the log-rank test to compare the groups. A two-tailed Z test for difference in proportions was done to analyze complications, local recurrence, 30-day and 90-day mortality. Results: A total of 108 patients underwent sleeve lobectomy (n=34) or pneumonectomy (n=74) for treatment of NSCLC with 18 undergoing open pneumonectomy, 56 undergoing video-assisted thoracoscopic surgery (VATS) pneumonectomy, 29 undergoing open sleeve lobectomy, and 5 undergoing VATS sleeve lobectomy. There was no significant difference in 30-day mortality (P=0.064) but there was a difference in 90-day (P=0.007). There was no difference in complication rates (P=0.234) or local recurrence rates (P=0.779). The pneumonectomy patients had a median survival of 23.6 months (95% CI: 3.8-43.4 months). The sleeve lobectomy group had a median survival of 60.7 months (95% CI: 43.3-78.2 months) (P=0.008). On multivariate analysis extent of resection (P<0.001) and tumor stage (P=0.036) were associated with survival. There was no significant difference between the VATS approach and the open surgical approach (P=0.053). Conclusions: When considering patients undergoing surgery for NSCLC sleeve lobectomy resulted in lower 90-day mortality and better 3-year survival compared to patients undergoing PN. Having a sleeve lobectomy rather than a pneumonectomy and having earlier-stage disease lead to significantly improved survival on multivariate analysis. Having a VATS operation leads to a non-inferior post-operative outcome compared to open surgery.

Impact of a Thoracic Multidisciplinary Conference on Lung Cancer Outcomes.

BACKGROUND: With the complexity of cancer treatment rising, the role of multidisciplinary conferences (MDCs) in making diagnostic and treatment decisions has become critical. This study evaluated the impact of a thoracic MDC (T-MDC) on lung cancer care quality and survival. METHODS: Lung cancer cases over 7 years were identified from the Roswell Park cancer registry system. The survival rates and treatment plans of 300 patients presented at the MDC were compared with 300 matched patients. The National Comprehensive Cancer Network (NCCN) guidelines were used to define the standard of care. The compliance of care plans with NCCN guidelines was summarized using counts and percentages, with comparisons made using the Fisher exact test. Survival outcomes were summarized using Kaplan-Meier methods. RESULTS: There was improvement in median overall survival (36.9 vs 19.3 months; P < .001) and cancer-specific survival (48 vs 28.1 months; P < .001) for lung cancer patients discussed at the T-MDC compared with controls. These differences were statistically significant in patients with stages III/IV disease but not in patients with stages I/II disease. The NCCN guidelines compliance rate of treatment plans improved from 80% to 94% (P < .001) after MDC discussion. MDC recommendations resulted in treatment plan changes in 123 of 300 patients (41%). CONCLUSIONS: Our results suggest that lung cancer patients have a survival benefit from MDC discussion compared with controls. Patients with advanced disease (stages III and IV) benefited the most. Further research is necessary to understand the precise mechanisms that drive these results.

Safety of thoracoscopic lobectomy in locally advanced lung cancer.

BACKGROUND: Thoracoscopic lobectomy is well established for the treatment of early non-small cell lung cancer (NSCLC). Its safety and efficacy for advanced-stage disease remain uncertain. METHODS: Between January 1, 2002, and July 31, 2007, a total of 125 patients were evaluated for thoracoscopic lobectomy for advanced NSCLC. Thoracoscopic lobectomy was completed in 73 patients. Eleven patients were excluded for extensive chest wall involvement. Open resection was performed in 41 patients, with 19 planned thoracotomies and 22 conversions from an initial thoracoscopic approach. RESULTS: Median operative blood loss, operation time, major complications, and hospital length of stay were all similar for patients undergoing thoracoscopic and open resection. A higher percentage of patients who underwent thoracoscopic lobectomy were able to receive adjuvant therapy compared to the open group (37.2% vs. 5.2%; P = 0.006). The differences between the thoracoscopic and open groups in overall survival (43.7 vs. 22.9 months; P = 0.59) and disease-free survival (34.7 vs. 16.7 months; P = 0.84) were not significant. CONCLUSIONS: Thoracoscopic lobectomy for advanced-stage NSCLC can be performed safely, with results equivalent to open techniques. With continued experience, lower morbidity with resections performed for advanced-stage disease by video-assisted thoracoscopic surgery will be expected, similar to that observed with early-stage disease. This is particularly important given the large number of frail patients with advanced-stage disease who require multimodal therapy.

Does circular stapled esophagogastric anastomotic size affect the incidence of postoperative strictures?

BACKGROUND: Postoperative anastomotic strictures produce significant morbidity after esophagectomy. Previous reports have described a variable association between the diameter of the circular end-to-end anastomosis (EEA) stapler commonly used in esophagogastric anastomoses and the incidence of stricture formation. Stapler technology has improved. We investigated an association between stapler diameter and the incidence of postoperative anastomotic strictures in a contemporary series. This has renewed importance given the limited diameter of trans-oral staplers that are being increasingly used. METHODS: Retrospective chart review revealed that of 194 patients undergoing an esophagectomy over a 10-y period (10/1998-8/2008) at our institution, an EEA stapler was used in 91. EEA size information and follow-up were available in 89 patients. Patients were divided into two groups based on EEA size: 'small' = 23-25 mm (n = 24) and 'large' = 28-33 mm (n = 65). Patients with strictures were identified based on symptoms of dysphagia requiring an esophageal dilation procedure. Patients with postoperative leaks were excluded when analyzing for the association of stricture with EEA size, as postoperative leaks are known to be associated with stricture. Wilcoxon and Fisher's exact tests were used for statistical analysis; a 5% α error was accepted. RESULTS: Fifteen (16.8%) of 89 patients developed a stricture postoperatively. The anastomotic leak rate was 3.3%. There was no statistically significant association between EEA size group and stricture formation (P = 0.7506). CONCLUSIONS: No association was found between the size of the EEA stapler used and stricture formation. EEA size should be determined at surgery by the native esophageal diameter.

Real-world challenges for patients with breast cancer in sub-Saharan Africa: a retrospective observational study of access to care in Ghana, Kenya and Nigeria.

OBJECTIVE: To evaluate medical resource utilisation and timeliness of access to specific aspects of a standard care pathway for breast cancer at tertiary centres in sub-Saharan Africa. DESIGN: Data were retrospectively abstracted from records of patients with breast cancer treated within a prespecified 2-year period between 2014 and 2017. The study protocol was approved by local institutional review boards. SETTING: Six tertiary care institutions in Ghana, Kenya and Nigeria were included. PARTICIPANTS: Health records of 862 patients with breast cancer were analysed: 299 in Ghana; 314 in Kenya; and 249 in Nigeria. INTERVENTIONS: As directed by the treating physician. OUTCOME MEASURES: Parameters selected for evaluation included healthcare resource and use, medical procedure turnaround times and out-of-pocket (OOP) payment patterns. RESULTS: Use of mammography or breast ultrasonography was <45% in all three countries. Across the three countries, 78%-88% of patients completed tests for hormone receptors and human epidermal growth factor receptor 2 (HER2). Most patients underwent mastectomy (64%-67%) or breast-conserving surgery (15%-26%). Turnaround times for key procedures, such as pathology, surgery and systemic therapy, ranged from 1 to 5 months. In Ghana and Nigeria, most patients (87%-93%) paid for diagnostic tests entirely OOP versus 30%-32% in Kenya. Similarly, proportions of patients paying OOP only for treatments were high: 45%-79% in Ghana, 8%-20% in Kenya and 72%-89% in Nigeria. Among patients receiving HER2-targeted therapy, the average number of cycles was five for those paying OOP only versus 14 for those with some insurance coverage. CONCLUSIONS: Patients with breast cancer treated in tertiary facilities in sub-Saharan Africa lack access to timely diagnosis and modern systemic therapies. Most patients in Ghana and Nigeria bore the full cost of their healthcare and were more likely to be employed and have secondary or postsecondary education. Access to screening/diagnosis and appropriate care is likely to be substantively lower for the general population.

Exceeding Radiation Dose to Volume Parameters for the Proximal Airways with Stereotactic Body Radiation Therapy Is More Likely for Ultracentral Lung Tumors and Associated with Worse Outcome.

The preferred radiotherapeutic approach for central (CLT) and ultracentral (UCLT) lung tumors is unclear. We assessed the toxicity and outcomes of patients with CLT and UCLT who underwent definitive five-fraction stereotactic body radiation therapy (SBRT). We reviewed the charts of patients with either CLT or UCLT managed with SBRT from June 2010-April 2019. CLT were defined as gross tumor volume (GTV) within 2 cm of either the proximal bronchial tree, trachea, mediastinum, aorta, or spinal cord. UCLT were defined as GTV abutting any of these structures. Propensity score matching was performed for gender, performance status, and history of prior lung cancer. Within this cohort of 83 patients, 43 (51.8%) patients had UCLT. The median patient age was 73.1 years with a median follow up of 29.9 months. The two most common dose fractionation schemes were 5000 cGy (44.6%) and 5500 cGy (42.2%) in five fractions. Multivariate analysis revealed UCLT to be associated with worse overall survival (OS) (HR = 1.9, p = 0.02) but not time to progression (TTP). Using propensity score match pairing, UCLT correlated with reduced non-cancer associated survival (p = 0.049) and OS (p = 0.03), but not TTP. Within the matched cohort, dosimetric study found exceeding a D4cc of 18 Gy to either the proximal bronchus (HR = 3.9, p = 0.007) or trachea (HR = 4.0, p = 0.02) was correlated with worse non-cancer associated survival. In patients undergoing five fraction SBRT, UCLT location was associated with worse non-cancer associated survival and OS, which could be secondary to excessive D4cc dose to the proximal airways.

Prior Treatment for Non-small Cell Lung Cancer Is Associated With Improved Survival in Patients who Undergo Definitive Stereotactic Body Radiation Therapy for a Subsequent Lung Malignancy: A Retrospective Multivariate and Matched Pair Analysis.

BACKGROUND: Despite occurring commonly, the prognoses of second early-stage non-small cell lung cancers (NSCLC) are not well known. METHODS: The authors retrospectively reviewed the charts of inoperable patients who underwent thoracic stereotactic body radiation therapy (SBRT) from February 2007 to April 2019. Those with previous small cell lung cancers or SBRT treatments for tumors other than NSCLC were excluded. Multivariate Cox regression and a matched pair cohort analyses evaluated the prognoses of patients undergoing definitive SBRT for a new second primary. RESULTS: Of 438 patients who underwent definitive SBRT for NSCLC, 84 had previously treated NSCLC. Univariate log-rank tests identified gender, Karnofksy performance status (KPS), prior lung cancer, anticoagulation use, and history of heart disease to correlate with overall survival (OS) (P<0.05). These factors were incorporated into a multivariate Cox regression model that demonstrated female sex (P=0.004, hazard ratio [HR]=0.68), KPS (P<0.001, HR=2.0), and prior lung cancer (P=0.049, HR=0.7) to be significantly associated with OS. A similar approach found only gender (P=0.017, HR=0.64) and tumor stage (P=0.02, HR=1.7) to correlate with relapse-free survival. To support the Cox regression analysis, propensity score matching was performed using gender, age, KPS, tumor stage, history of heart disease, and anticoagulation use. Kaplan-Meier survival analysis within the matched pairs found prior lung cancer to be associated with improved OS (P=0.011), but not relapse-free survival (P=0.44). CONCLUSIONS: Compared with initial lung cancer SBRT inoperable cases, ablative radiotherapy for new primaries was associated with improved OS. Physicians should not be dissuaded from offering SBRT to such patients.

Cruciferous vegetable intake is inversely associated with lung cancer risk among smokers: a case-control study.

BACKGROUND: Inverse associations between cruciferous vegetable intake and lung cancer risk have been consistently reported. However, associations within smoking status subgroups have not been consistently addressed. METHODS: We conducted a hospital-based case-control study with lung cancer cases and controls matched on smoking status, and further adjusted for smoking status, duration, and intensity in the multivariate models. A total of 948 cases and 1743 controls were included in the analysis. RESULTS: Inverse linear trends were observed between intake of fruits, total vegetables, and cruciferous vegetables and risk of lung cancer (ORs ranged from 0.53-0.70, with P for trend < 0.05). Interestingly, significant associations were observed for intake of fruits and total vegetables with lung cancer among never smokers. Conversely, significant inverse associations with cruciferous vegetable intake were observed primarily among smokers, in particular former smokers, although significant interactions were not detected between smoking and intake of any food group. Of four lung cancer histological subtypes, significant inverse associations were observed primarily among patients with squamous or small cell carcinoma - the two subtypes more strongly associated with heavy smoking. CONCLUSIONS: Our findings are consistent with the smoking-related carcinogen-modulating effect of isothiocyanates, a group of phytochemicals uniquely present in cruciferous vegetables. Our data support consumption of a diet rich in cruciferous vegetables may reduce the risk of lung cancer among smokers.

Analysis of second primary lung cancers in the SEER database.

BACKGROUND: We sought to examine the outcomes of second primary lung cancers in the large population-based Surveillance Epidemiology and End Results (SEER) database. We also sought to study the outcomes of synchronous second non-small-cell lung cancers (NSCLCs), classified as stage IVA (M1A) according to the seventh edition of the TNM staging for lung cancer. METHODS: Data of patients with at least two primary lung cancers were obtained. All available variables potentially associated with the incidence of a second primary lung cancer were examined. The overall survival of patients with synchronous NSCLC was compared with those with metachronous and stage IV NSCLC. RESULTS: A small proportion (1.5%) of patients with lung cancer developed a second primary. A second primary is associated with younger age, female gender, earlier stage, and white race. The median survival of patients with metachronous NSCLCs (n = 3352) was worse than those with synchronous NSCLCs (n = 1858) (median survival 22 mo versus 29 mo, respectively; P < 0.01). After adjusting for age, race, gender, stage, and histology of both primaries, this difference in survival between patients with synchronous and metachronous second primary lung cancers was not statistically significant, but was better than those with stage IV NSCLC (n = 127,654; median survival 4 mo). CONCLUSIONS: The incidence of second primary lung cancer is lower than that previously reported. Factors associated with good prognosis predict a second primary. Synchronous NSCLCs have an outcome better than a stage IV (M1a) designation. These patients should receive appropriate stage-specific multi-modality therapy suitable for the independent stage of each cancer without considering them unresectable.

Minimally Invasive Ivor Lewis Esophagectomy with Linear Stapled Anastomosis Associated with Low Leak and Stricture Rates.

BACKGROUND: Minimally invasive foregut surgery is increasingly performed for both benign and malignant diseases. We present a retrospective series of patients who underwent minimally invasive Ivor Lewis esophagectomy (MIE) with linear stapled anastomosis performed at two centers in the USA, with a focus on evaluating leak and stricture rates. METHODS: Patients treated from 2007 to 2018 were included, and data on demographics, oncologic treatment, pathology, and outcomes were analyzed. The surgical technique utilized laparoscopic and thoracoscopic access, with an intrathoracic esophagogastric anastomosis using a 6-cm linear stapled side-to-side technique. RESULTS: A total of 124 patients were included and 114 resections (91.9%) were completed in a minimally invasive fashion with a 6-cm linear stapled side-to-side anastomosis. Patients were predominantly male (90.7%) with a median age of 66.0 years and body mass index of 28.8 kg/m2. Of 121 patients with malignancy, negative margins were obtained in 94.3% and median lymph node yield was 15 (IQR 12-22). In the intention to treat analysis, median operative time was 463 min (IQR 403-515), blood loss was 150 mL (IQR 100-200), and length of stay was 8 days (IQR 7-11). Postoperative complications were experienced by 64 patients (51.6%) including respiratory failure in 14 (11.3%) and pneumonia in 12 (9.7%). In patients who successfully underwent a 6-cm stapled side-to-side anastomosis, anastomotic leaks occurred in 6 patients (5.1%) without need for operative intervention, and anastomotic strictures occurred in 6 patients (5.1%) requiring endoscopic management. CONCLUSIONS: Ivor Lewis MIE with a 6-cm linear stapled anastomosis can be completed with a high technical success rate, and low rates of anastomotic leak and stricture.