Impact of Detecting Occult Pathologic Nodal Disease During Resection for Malignant Pleural Mesothelioma.

BACKGROUND: Lymph node (LN) involvement is a poor prognostic factor for malignant pleural mesothelioma (MPM). However, to our knowledge, postresection outcomes of node-negative (cN0/pN0), occult pathologic nodal disease (cN0/pN+), and clinical node-positive disease (cN+) have not been compared to date. PATIENTS AND METHODS: The National Cancer Data Base was queried for newly diagnosed, resected MPM with known clinical/pathologic LN information. Three cohorts were compared: cN0/pN0, cN+, and cN0/pN+. Multivariable logistic regression examined predictors of pathologic nodal upstaging. Kaplan-Meier analysis with propensity matching assessed overall survival (OS); multivariate Cox proportional hazards modeling examined predictors thereof. RESULTS: Of 1369 patients, 687 (50%) had cN0/pN0, 457 (33%) cN+, and 225 (16%) cN0/pN+ disease. Median follow-up was 29 months. In patients with cN0 disease, factors associated with pathologic nodal upstaging were younger age, greater number of examined LNs, and nonsarcomatoid histology (P < .05 for all). Relative to pN0 cases, occult LN involvement (65% being pN2) was associated with 51% higher hazard of mortality on multivariate analysis (P = .005). Following propensity matching, the OS of cN0/pN+ was similar to cN+ cases (P = .281). On multivariate analysis, the number of involved LNs (continuous variable, P = .013), but not nodal tumor, node, metastasis (TNM) classification or LN ratio (P > .05 for both), was associated with OS. CONCLUSION: Detecting occult nodal disease during resection for cN0 MPM is associated with poorer prognosis, with similar survival as cN+ cases, underscoring the importance of routine preoperative pathologic nodal assessment for potentially resectable MPM. The number of involved LNs (rather than current location-based classification) may provide more robust prognostic stratification for future TNM staging.

Microsatellite Instability (MSI) as an Independent Predictor of Pathologic Complete Response (PCR) in Locally Advanced Rectal Cancer: A National Cancer Database (NCDB) Analysis.

OBJECTIVE: The relationship between microsatellite instability (MSI) and response to neoadjuvant chemoradiation in rectal cancer is not well understood. BACKGROUND: We utilized the National Cancer Database (NCDB) to investigate the association between MSI and pathologic complete response (pCR) in this patient population. METHODS: We analyzed 5086 patients between 2010 and 2015 with locally advanced rectal cancer who were tested for MSI and treated definitively with chemoradiation followed by surgery. Primary comparison groups were between 4450 MSI-negative(-) and 636 MSI-positive(+) patients. Multivariable regression analysis was conducted to identify demographic, therapeutic, and clinical characteristics predictive of pCR. Cox proportional-hazard ratios were used for survival. RESULTS: All patients were treated with definitive chemoradiation (median dose 50.4 Gy) followed by resection within 4 months. MSI(+) patients were associated with earlier year of diagnosis and higher-grade tumors (P < 0.05).The overall pCR rate was 8.6%, including 8.9% for MSI(-) and 5.9% for MSI(+) tumors (P = 0.01). Along with lower T stage, MSI(+) cases were significantly associated with a reduced pCR rate (odds ratio 0.65, 95% confidence interval 0.43-0.96) with multivariable analysis. The 5-year survival for patients with pCR was 93% compared with 73% without it (<0.001). CONCLUSION: Microsatellite instability was independently associated with a reduction in pCR for locally advanced rectal cancer after neoadjuvant chemoradiation in this NCDB-based analysis.

National patterns of care for early-stage penile cancers in the United States: How is radiation and brachytherapy utilized?

PURPOSE: Per American Brachytherapy Society guidelines, cT1-2N0 penile cancers <4 cm in diameter are excellent candidates for curative brachytherapy. Using that criterion, we evaluated national patterns of care and predictors of use of radiation techniques using the National Cancer Database. METHODS AND MATERIALS: The National Cancer Database was queried for men with cT1-2N0 penile cancers <4 cm in size. Comparative statistics for treatment modality were generated using bivariate logistic regression analysis. RESULTS: Among 1235 cases eligible for analysis, median age was 69 years. Median tumor size was 2.0 cm. 95.8% of men underwent surgery alone, with 91 (7.4%) undergoing radical penectomy, 673 (54.5%) partial penectomy, and 419 (33.9%) cosmesis-preserving surgical procedure. Only 4 (0.3%) men were treated with brachytherapy alone, 48 (3.9%) with external-beam radiation therapy (EBRT) alone, and 8 (0.6%) with EBRT after surgery. Surgical margins were positive in 118 (9.6%) patients, 14 of whom received adjuvant EBRT (11.9%) and two adjuvant brachytherapy (1.7%). There was no difference in demographic or clinical characteristics in groups treated with surgery vs. radiation (all p > 0.2). Age >70, lesions >2 cm, and T2 tumors were more likely to undergo non-organ-preserving therapy vs. radiation or a cosmesis-preserving procedure (all p < 0.05). The propensity-matched 5-year survival was not different between definitive radiation vs. surgery (61.6% vs. 62.2%, p = 0.70). CONCLUSIONS: Men with penile-preserving eligible lesions in the United States are overwhelmingly treated with surgery. Penile-preserving radiation techniques including brachytherapy and EBRT are underutilized and should be offered as curative interventions.

Chemotherapy Versus Supportive Care for Unresected Malignant Pleural Mesothelioma.

BACKGROUND: Management options for unresected malignant pleural mesothelioma (MPM) are largely limited to palliative chemotherapy and best supportive care. This study sought to delineate subgroups most likely to benefit from chemotherapy. PATIENTS AND METHODS: The National Cancer Database was queried for newly-diagnosed unresected sarcomatoid, biphasic, and/or metastatic (M1) MPM. Statistics included Kaplan-Meier overall survival (OS) analysis with and without propensity matching, landmark Kaplan-Meier analysis to address immortal time bias, and multivariable Cox proportional hazards modeling in all patients as well as within histologic/M-classification-based subcohorts. RESULTS: Of 4655 patients (48% chemotherapy, 52% best supportive care), 15%, 27%, and 40% had epithelioid, biphasic, and sarcomatoid disease, respectively; 41% had M1 disease. The median OS in the chemotherapy and BSC cohorts was 10.4 versus 4.8 months (P < .001). OS differences persisted following landmark analysis (P = .038) and propensity matching (P < .001). Chemotherapy was associated with higher OS in M1 cases with unknown histology and M1 epithelioid patients (P < .001 for both). For non-epithelioid cases, chemotherapy was associated with higher OS for M0 (P < .001 for sarcomatoid and biphasic) but not M1 (P > .05 for both) disease. CONCLUSIONS: Chemotherapy may benefit metastatic epithelioid and non-metastatic non-epithelioid MPM to a greater degree than metastatic non-epithelioid disease. Causation, however, is not implied, and careful patient selection in this population cannot be understated.

Survival Outcomes After Surgical Management of the Primary Tumor With and Without Radiotherapy for Metastatic Rectal Adenocarcinoma: A National Cancer Database (NCDB) Analysis.

BACKGROUND: With advances in systemic therapies, the role of primary tumor resection may be of increased importance in patients with metastatic rectal cancer. The role of combining pelvic radiotherapy with surgical resection in the metastatic setting is unknown. We utilized the National Cancer Database to examine outcomes in patients with metastatic rectal adenocarcinoma with primary tumor resection with and without pelvic radiotherapy. MATERIALS AND METHODS: We queried the National Cancer Database from 2004 to 2014 for patients with stage IV rectal adenocarcinoma receiving chemotherapy. We identified 4051 patients in that group that had primary tumor resection. Patients were then stratified by receipt of pelvic radiotherapy (yes = 1882; no = 2169) Univariable and multivariable analyses identified characteristics predictive of overall survival. Propensity-adjusted Cox proportional hazard ratios for survival were used to account for indication bias. RESULTS: The median patient age was 63 years (range, 18-90 years) with a median follow-up of 32.3 months (range, 3.02-151.29 months). There were proportionately more patients with T3/T4 disease or N1 disease in the surgery plus radiotherapy arm. The median survival was 46.3 months versus 35.3 months in favor of addition of radiotherapy (P < .001). The 2- and 5-year overall survival was 68.4% and 24.8% for surgical resection alone compared with 77.2% and 39.6% for surgery + radiotherapy. On propensity-adjusted multivariable analysis, radiotherapy was associated with a statistically significant reduction in risk of death (hazard ratio, 0.722; 95% confidence interval, 0.0665-0.784). CONCLUSION: This analysis indicates that in patients with metastatic rectal adenocarcinoma receiving chemotherapy, pelvic radiotherapy in addition to primary tumor resection may be of significant benefit.

Fractionated stereotactic radiosurgery for large brain metastases.

OBJECTIVES: Large brain metastases (>3 cm) present a therapeutic dilemma, as the dose delivered by stereotactic radiosurgery (SRS) in a single fraction is limited by toxicity to adjacent tissues, resulting in suboptimal local control. This study assessed the efficacy and safety of fractionated SRS for the treatment of large brain metastases. MATERIALS AND METHODS: We identified 36 patients with 37 brain metastases treated with fractionated SRS. The median SRS dose was 24 Gy (range, 12 to 27 Gy) in 2 to 5 fractions and the median treatment volume was 15.6 mL (range, 10 to 82.7 mL). Kaplan-Meier analysis was used to estimate local control and overall survival rates. RESULTS: Of the 21 lesions with available radiographic follow-up, 6 lesions (29%) had a documented local failure, yielding an actuarial progression-free survival at 6 and 12 months of 73% and 63%, respectively. The actuarial 6-month and 1-year overall survival rates were 22% and 13%, respectively. No patients in this cohort experienced acute or late complications secondary to SRS. CONCLUSIONS: Fractionated SRS is feasible and safe in patients with large brain metastases. Local control rates appear to be improved when compared with that of single fraction SRS with a relative paucity of treatment-related toxicity.