Surgical Approach and Persistent Opioid Use in Medicare Patients Undergoing Lung Cancer Resection.

BACKGROUND: Robotic and video-assisted thoracoscopic surgery (VATS) approaches for lung resection are associated with decreased inpatient opioid use compared with open surgery. Whether these approaches affect outpatient persistent opioid use remains unknown. METHODS: Non-small cell lung cancer patients aged 66 years or more who underwent lung resection between 2008 and 2017 were identified from the Surveillance, Epidemiology, and End Results-Medicare database. Persistent opioid use was defined as filling an opioid prescription 3 to 6 months after lung resection. Adjusted analyses were performed to evaluate surgical approach and persistent opioid use. RESULTS: We identified 19,673 patients: 7479 (38%) underwent open surgery, 10,388 (52.8%) VATS, and 1806 (9.2%) robotic surgery. Persistent opioid use was 38% in the entire cohort, including 27% of opioid naïve patients, and highest after open surgery (42.5%), followed by VATS (35.3%) and robotic (33.1%, P < .001). In multivariable analyses, robotic (odds ratio 0.84; 95% CI, 0.72-0.98; P = .028) and VATS (odds ratio 0.87; 95% CI, 0.79-0.95; P = .003) approaches were both associated with decreased persistent opioid use compared with open surgery in opioid naïve patients. At 12 months, patients resected using a robotic approach had the lowest oral morphine equivalent per month compared with VATS (133 vs 160, P < .001) and open surgery (133 vs 200, P < .001). Among chronic opioid patients, surgical approach was not associated with postoperative opioid use. CONCLUSIONS: Persistent opioid use after lung resection is common. Both robotic and VATS approaches were associated with decreased persistent opioid use compared with open surgery among opioid naïve patients. Whether a robotic approach yields additional long-term advantages over VATS warrants further investigation.

Neoadjuvant chemoradiotherapy followed by surgery for esophageal adenocarcinoma: significance of microscopically positive circumferential radial margins.

OBJECTIVES: The incidence and consequence of an isolated involved circumferential radial margin (CRM) after resection for esophageal adenocarcinoma in the setting of neoadjuvant chemoradiotherapy (CRT) has not been reported. We aimed to determine the frequency and significance of a close (<1 mm) or involved CRM in patients undergoing esophagectomy after CRT. METHODS: We retrospectively analyzed the data from patients undergoing resection from 1997 to 2008 for esophageal adenocarcinoma after neoadjuvant CRT. A positive CRM was defined as microscopic tumor at or less than 1 mm of the radial margin. An R1 resection was tumor at the radial margin. Only patients with ypT3 or greater tumors were included. R2 resections were excluded. Statistical comparisons were performed using Cox regression and Kaplan-Meier analyses. RESULTS: A total of 160 patients met the inclusion criteria, 42 (26%) had a positive CRM. The median survival did not significantly differ between the CRM-negative and -positive groups (28 vs 50 months, P = .84). A propensity score matching analysis also failed to find a significant difference in outcomes. When analyzed by tumor present at the margin (R1), R0 patients had a longer median survival compared with R1 patients (28 vs 8 months, P = .01). This difference, however, was not seen on propensity score matching. CONCLUSIONS: Resections of locally advanced esophageal adenocarcinoma with residual transmural viable tumor after CRT frequently showed involvement of the radial margin with tumor either close to or at the margin. Tumor close (<1 mm) to the radial margin did not result in a significant decrease in overall or disease-free survival or increase in local recurrence.

Outcomes after surgical resection of cardiac sarcoma in the multimodality treatment era.

OBJECTIVE: Primary cardiac sarcomas are rare tumors carrying poor prognosis. Resection remains the primary therapy. Especially in recent years, chemotherapy and radiation have been used adjunctively. METHODS: All patients (n = 27) surgically treated for primary cardiac sarcoma at two tertiary referral centers from January 1990 to January 2006 were retrospectively reviewed. RESULTS: There were 13 women and 14 men, with 26 resections and 1 palliative debulking performed. Cardiac explantation was necessary in 8 cases because of tumor location. Concomitant valve surgery (repair or replacement) or coronary artery bypass grafting was performed in 9 and 3 patients, respectively. Synchronous or staged resections of associated pulmonary metastases were performed in 6 and 2 patients, respectively. Operative mortality was 7.4% (2/27). Preoperative or postoperative chemotherapy was administered to 16 and 19 patients, respectively. At follow-up (median 22 months, range, 2-119 months), 12 patients were alive, with 7 tumor free. Among patients who underwent resection with curative intent and survived surgery (n = 24), median survival was 23.5 months (range 4-119 months). Patients who underwent surgical resection, radiofrequency ablation, or radiation treatment for tumor recurrence (local or metastatic, n = 7) had median survival of 47 months (range 16-119 months), whereas patients with no further intervention for recurrent disease (n = 7) had median survival of 25 months (range 8-34 months). CONCLUSIONS: Multimodal therapy can achieve reasonable survival for patients with resected cardiac sarcomas. Patients with local tumor recurrence or metastatic disease may still benefit from aggressive treatment.

Expression of Delta DNMT3B variants and its association with promoter methylation of p16 and RASSF1A in primary non-small cell lung cancer.

Despite the role of DNMT3B in de novo DNA methylation, a correlation between DNMT3B expression and promoter DNA methylation has not being established in tumors. We recently reported DeltaDNMT3B, a subfamily of DNMT3B, with seven variants, as the predominant expression forms in non-small cell lung cancer (NSCLC). We hypothesized that expression of the DeltaDNMT3B variants plays a role in promoter methylation formation during lung tumorigenesis. Expression of seven DeltaDNMT3B variants was measured in 119 NSCLCs and the corresponding normal lungs using reverse transcription-PCR. The expression patterns of DeltaDNMT3B variants were analyzed with the status of p16 and RASSF1A promoter methylation in the tumors as well as in patients' clinical variables, including outcomes. Expression of DeltaDNMT3B variants was detected in 94 of 119 (80%) tumors but in only 22 (18%) of the corresponding normal lungs (P < 0.0001). DeltaDNMT3B1, DeltaDNMT3B2, and DeltaDNMT3B4 were the most frequently detected transcripts in the tumors (62%, 76%, and 46%, respectively). The expression of DeltaDNMT3B variants was associated with p16 and RASSF1A promoter methylation in the tumors, but the strongest association was between DeltaDNMT3B4 and RASSF1A. Forty-two of 46 (91%) tumors with RASSF1A promoter methylation expressed DeltaDNMT3B4 compared with only 13 of 73 (18%) tumors without the promoter methylation (P < 0.0001). Strong associations were also observed between expression of the variants in the tumors and in patients' clinical outcomes. Expression of DeltaDNMT3B variants is common in NSCLC and may play an important role in the development of promoter methylation.

Induction chemotherapy improved outcomes of patients with resectable esophageal cancer who received chemoradiotherapy followed by surgery.

PURPOSE: To investigate the effect of induction chemotherapy (CHT) before trimodality therapy on the outcome of patients with resectable cancer of the esophagus. METHODS AND MATERIALS: This retrospective study included 81 consecutive patients with resectable cancer of the esophagus who received neoadjuvant chemoradiotherapy followed by esophagectomy between January 1990 and December 1998 (inclusive). Thirty-nine patients underwent chemoradiotherapy followed by esophagectomy (CHT/RT+S), 42 received additional induction CHT followed by CHT/RT+S (CHT+CHT/RT+S). Of the 81 patients, 47 were entered in institutional or national prospective trials (6 in the CHT/RT+S and 41 in the CHT+CHT/RT+S group). Induction CHT consisted of three courses of 5-fluorouracil (5-FU), cisplatin, and paclitaxel given in 28-day cycles in 37 patients (88.1%). Concurrent CHT was 5-FU and platinum based. The median radiation dose for patients treated with CHT/RT+S was 30 Gy (range, 30-50.4 Gy) delivered in a median of 10 fractions (range, 10-28 fractions) and 45 Gy (range, 30-45 Gy) in a median of 25 fractions (range, 10-25 fractions) for patients treated with CHT+CHT/RT+S. Esophagectomy was performed 6-8 weeks after completion of concurrent chemoradiotherapy. Most patients underwent transthoracic esophagectomy (n = 66, 82.5%). RESULTS: The pretreatment characteristics were well balanced between the two groups except for age. The median follow-up time was 29 months (22 months for the CHT/RT+S group and 38.5 months for the CHT+CHT/RT+S group) for all patients and 49 months for living patients. The actuarial overall survival (OS), disease-free survival (DFS), locoregional control (LRC), and distant metastasis-free survival (DMFS) rate at 5 years for the entire group was 46%, 36.6%, 70.7%, and 53.2%, respectively. Statistically significant differences in the OS, DFS, and LRC rates between the two groups were detected. Specifically, the 5-year OS rate was 22.8% and 71.1% in the CHT/RT+S and CHT+CHT/RT+S group (p = 0.0001), respectively. The 5-year DFS rate was 27.6% and 56.6% in the CHT/RT+S and CHT+CHT/RT+S group (p = 0.003), respectively. The 5-year LRC rate was 64.2% and 85.6% in the CHT/RT+S and CHT+CHT/RT+S group (p = 0.007), respectively. The difference in the DMFS rate between the two groups was statistically significant, with a 2- and 5-year actuarial rate of 63.9% and 51.9%, respectively, in the CHT/RT+S group and 76.9% and 74.1%, respectively, in the CHT+CHT/RT+S group (p = 0.04). The statistically significant differences persisted when patients who received >/=45 Gy in each group were compared. Among those patients, the 5-year OS, DFS, LRC, and DMFS rates were 23.1%, 15.4%, 58.6%, and 39.2%, respectively, for those receiving CHT/RT+S, and 71.4% (p = 0.001), 55.8% (p = 0.0008), 84.6% (p = 0.005), and 77.3% (p = 0.009), respectively, for those receiving CHT+CHT/RT+S. The pathologic complete response (pCR) rate was greater in the CHT+CHT/RT+S group compared with in the CHT/RT+S group (p = 0.008). In univariate analysis, young age, good Karnofsky performance status, Stage II disease, total radiation dose, multiple drug regimen for concurrent CHT, pCR, R0 resection, distant disease progression, and CHT+CHT/RT+S treatment proved to be prognostic factors for OS. Lower esophageal/gastroesophageal junction tumor location, pCR, R0 resection, and CHT+CHT/RT+S treatment were favorable prognostic factors for LRC. Neither the total radiation dose nor multiple drugs for concurrent CHT were negative prognostic factors for LRC. In multivariate analysis, pCR, R0 resection, and treatment with CHT+CHT/RT+S were independent positive predictive factors for OS, and distant recurrences were negative predictive factors for OS. R0 resection, CHT+CHT/RT+S treatment, and lower esophageal/gastroesophageal junction tumor location were positive predictive factors for LRC. The radiation dose was not identified as an independent prognostic factor for either OS or LRC in the multivariate analysis. Meaningful multivariate analysis could not be performed when the multiple drug vperformed when the multiple drug variable was included in the model because of the small number of patients. CONCLUSION: Significantly greater LRC, DFS, OS, and DMFS were found in patients treated with CHT+CHT/RT+S compared with those treated with CHT/RT+S. The pCR rate was significantly higher in the CHT+CHT/RT+S group. Induction CHT was an independent favorable prognostic factor for both LRC and OS for the population included in this study. Our data suggest that a randomized trial comparing CHT+CHT/RT+S and CHT/RT+S is warranted to assess further the merits of this treatment in patients with this currently very lethal cancer.

Surgical management of renal cell carcinoma associated with complex inferior vena caval thrombi.

The operative morbidity and mortality of radical nephrectomy are considerably higher when the vena cava is involved by the tumor. The prognostic significance of vena caval extension in this setting remains controversial. We reviewed our experience of vena caval thrombectomy specifically addressing prognostic factors. We retrospectively studied 96 patients treated at our institution between 1985 and 2001. The study population included 28 women and 68 men; (37 left- and 59 right-sided tumors). Twenty-seven patients had metastatic disease at presentation. Prognostic features (age, sex, race, side of tumor, embolization, tumor grade, tumor confinement by renal capsule, cephalic extent of thrombus, nodal status, and presence of distant metastasis) were evaluated using a Cox proportional hazards model (univariate and multivariate). These prognostic features were analyzed in the group as a whole and in the subgroup of patients who did not have metastatic disease at presentation and did not die perioperatively. There were 5 perioperative deaths. Extracapsular tumor extension and regional node involvement were present in 64% and 17% of the patients, respectively. Level of tumor thrombus were as follows: level I (41%), II (29%), III (7%), IV (15%). Fuhrman's grade was 2 in 17%, 3 in 45%, and 4 in 30% of the patients. For all 96 patients, median overall survival (OS) was 35 months. Five-year OS was 35%. The presence of distant metastasis at presentation did not significantly alter median OS (20 months with metastasis vs. 38 months without, P = 0.3), although this finding may have been confounded by selection. The presence of nodal metastasis was associated with decreased OS by multivariate analysis (P < 0.01). After exclusion of patients dying perioperatively and patients with metastasis at presentation, median OS and progression-free survival were 40 and 18 months, respectively (5-year OS was 40%). In the multivariate model, none of the factors examined were associated with OS, but age <58 years, and the presence of extracapsular tumor extension were associated with an increased risk of recurrence. In patients with renal tumors and extension of tumor thrombus into the vena cava, the level of propagation of the thrombus does not predict for OS. Selected patients with metastatic renal cancer may benefit from aggressive surgical resection of the primary tumor and associated tumor thrombus.