Preoperative Radiosurgery for Resected Brain Metastases: The PROPS-BM Multicenter Cohort Study.

PURPOSE: Preoperative radiosurgery (SRS) is a feasible alternative to postoperative SRS, with potential benefits in adverse radiation effect (ARE) and leptomeningeal disease (LMD) relapse. However, previous studies are limited by small patient numbers and single-institution designs. Our aim was to evaluate preoperative SRS outcomes and prognostic factors from a large multicenter cohort (Preoperative Radiosurgery for Brain Metastases [PROPS-BM]). METHODS AND MATERIALS: Patients with brain metastases (BM) from solid cancers who had at least 1 lesion treated with preoperative SRS and underwent a planned resection were included from 5 institutions. SRS to synchronous intact BM was allowed. Radiographic meningeal disease (MD) was categorized as either nodular or classical "sugarcoating" (cLMD). RESULTS: The cohort included 242 patients with 253 index lesions. Most patients (62.4%) had a single BM, 93.7% underwent gross total resection, and 98.8% were treated with a single fraction to a median dose of 15 Gray to a median gross tumor volume of 9.9 cc. Cavity local recurrence (LR) rates at 1 and 2 years were 15% and 17.9%, respectively. Subtotal resection (STR) was a strong independent predictor of LR (hazard ratio, 9.1; P < .001). One and 2-year rates of MD were 6.1% and 7.6% and of any grade ARE were 4.7% and 6.8% , respectively. The median overall survival (OS) duration was 16.9 months and the 2-year OS rate was 38.4%. The majority of MD was cLMD (13 of 19 patients with MD; 68.4%). Of 242 patients, 10 (4.1%) experienced grade ≥3 postoperative surgical complications. CONCLUSIONS: To our knowledge, this multicenter study represents the largest cohort treated with preoperative SRS. The favorable outcomes previously demonstrated in single-institution studies, particularly the low rates of MD and ARE, are confirmed in this expanded multicenter analysis, without evidence of an excessive postoperative surgical complication risk. STR, though infrequent, is associated with significantly worse cavity LR. A randomized trial between preoperative and postoperative SRS is warranted and is currently being designed.

Leptomeningeal disease and neurologic death after surgical resection and radiosurgery for brain metastases: A multi-institutional analysis.

PURPOSE: Postoperative stereotactic radiosurgery (SRS) is associated with up to 30% risk of subsequent leptomeningeal disease (LMD). Radiographic patterns of LMD (classical sugarcoating [cLMD] vs. nodular [nLMD]) in this setting has been shown to be prognostic. However, the association of these findings with neurologic death (ND) is not well described. METHODS AND MATERIALS: The records for patients with brain metastases who underwent surgical resection and adjunctive SRS to 1 lesion (SRS to other intact lesions was allowed) and subsequently developed LMD were combined from 7 tertiary care centers. Salvage radiation therapy (RT) for LMD was categorized according to use of whole-brain versus focal cranial RT. RESULTS: The study cohort included 125 patients with known cause of death. The ND rate in these patients was 79%, and the rate in patients who underwent LMD salvage treatment (n = 107) was 76%. Univariate logistic regression demonstrated radiographic pattern of LMD (cLMD vs. nLMD, odds ratio: 2.9; P = .04) and second LMD failure after salvage treatment (odds ratio: 3.9; P = .02) as significantly associated with ND. The ND rate was 86% for cLMD versus 68% for nLMD. Whole-brain RT was used in 95% of patients with cLMD and 52% with nLMD. In the nLMD cohort (n = 58), there was no difference in ND rate based on type of salvage RT (whole-brain RT: 67% vs. focal cranial RT: 68%, P = .92). CONCLUSIONS: LMD after surgery and SRS for brain metastases is a clinically significant event with high rates of ND. Classical LMD pattern (vs. nodular) and second LMD failure after salvage treatment were significantly associated with a higher risk of ND. Patients with nLMD treated with salvage focal cranial RT did not have higher ND rates compared with WBRT. Methods to decrease LMD and the subsequent high risk of ND in this setting warrant further investigation.

Evaluating Potential Racial Inequities in Low-dose Computed Tomography Screening for Lung Cancer.

BACKGROUND: Lung cancer is the leading cause of cancer death in the US, and significant racial disparities exist in lung cancer outcomes. For example, Black men experience higher lung cancer incidence and mortality rates than their White counterparts. New screening recommendations for low-dose computed tomography (LDCT) promote earlier detection of lung cancer in at-risk populations and can potentially help mitigate racial disparities in lung cancer mortality if administered equitably. Yet, little is known about the extent of racial differences in uptake of LDCT. OBJECTIVE: To evaluate potential racial disparities in LDCT screening in a large community-based cancer center in central North Carolina. METHODS: We conducted a retrospective study of the initial patients undergoing LDCT in a community-based cancer center (n = 262). We used the Pearson chi-squared test to assess potential racial disparities in LDCT screening. RESULTS: Study results suggest that Black patients may be less likely than White patients to receive LDCT screening when eligible (χ2 = 51.41, p < 0.0001). CONCLUSION: Collaboration among healthcare providers, researchers, and decision makers is needed to promote LDCT equity.

A Multi-faceted Intervention Aimed at Black-White Disparities in the Treatment of Early Stage Cancers: The ACCURE Pragmatic Quality Improvement trial.

BACKGROUND: Reports continue to show that Blacks with curable lung or breast cancer complete treatment less often than similar Whites contributing to worse survival. ACCURE is an intervention trial designed to address this problem. PATIENTS AND METHODS: A pragmatic, quality improvement trial comparing an intervention group to retrospective and concurrent controls. Patients with early stage breast or lung cancer aged 18 to 85 were enrolled (N = 302) at 2 cancer centers between April 2013 and March 2015 for the intervention component. Data from patients seen between January 2007 and December 2012 with these diagnoses were obtained to establish control completion rates. Concurrent data for non-study patients were used to identify secular trends. The intervention included: a real time registry derived from electronic health records of participants to signal missed appointments or unmet care milestones, a navigator, and clinical feedback. The primary outcome was "Treatment Complete", a composite variable representing completion of surgery, recommended radiation and chemotherapy for each patient. RESULTS: The mean age in the intervention group was 63.1 years; 37.1% of patients were Black. Treatment completion in retrospective and concurrent controls showed significant Black-White differences (Blacks (B) 79.8% vs. Whites (W) 87.3%, p < 0.001; 83.1% B vs. 90.1% W, p < 0.001, respectively). The disparity lessened within the intervention (B 88.4% and W 89.5%, p = 0.77). Multivariate analyses confirmed disparities reduction. OR for Black-White disparity within the intervention was 0.98 (95% CI 0.46-2.1); Black completion in the intervention compared favorably to Whites in retrospective (OR 1.6; 95% CI 0.90-2.9) and concurrent (OR 1.1; 95% CI 0.59-2.0) controls. CONCLUSION: A real time registry combined with feedback and navigation improved completion of treatment for all breast and lung cancer patients and narrowed disparities. Similar multi-faceted interventions could mitigate disparities in the treatment of other cancers and chronic conditions.

A multi-institutional analysis of presentation and outcomes for leptomeningeal disease recurrence after surgical resection and radiosurgery for brain metastases.

BACKGROUND: Radiographic leptomeningeal disease (LMD) develops in up to 30% of patients following postoperative stereotactic radiosurgery (SRS) for brain metastases. However, the clinical relevancy of this finding and outcomes after various salvage treatments are not known. METHODS: Patients with brain metastases, of which 1 was resected and treated with adjunctive SRS, and who subsequently developed LMD were combined from 7 tertiary care centers. LMD pattern was categorized as nodular (nLMD) or classical ("sugarcoating," cLMD). RESULTS: The study cohort was 147 patients. Most patients (60%) were symptomatic at LMD presentation, with cLMD more likely to be symptomatic than nLMD (71% vs. 51%, P = 0.01). Salvage therapy was whole brain radiotherapy (WBRT) alone (47%), SRS (27%), craniospinal radiotherapy (RT) (10%), and other (16%), with 58% receiving a WBRT-containing regimen. WBRT was associated with lower second LMD recurrence compared with focal RT (40% vs 68%, P = 0.02). Patients with nLMD had longer median overall survival (OS) than those with cLMD (8.2 vs 3.3 mo, P < 0.001). On multivariable analysis for OS, pattern of initial LMD (nodular vs classical) was significant, but type of salvage RT (WBRT vs focal) was not. CONCLUSIONS: Nodular LMD is a distinct pattern of LMD associated with postoperative SRS that is less likely to be symptomatic and has better OS outcomes than classical "sugarcoating" LMD. Although focal RT demonstrated increased second LMD recurrence compared with WBRT, there was no associated OS detriment. Focal cranial RT for nLMD recurrence after surgery and SRS for brain metastases may be a reasonable alternative to WBRT.

A system-based intervention to reduce Black-White disparities in the treatment of early stage lung cancer: A pragmatic trial at five cancer centers.

BACKGROUND: Advances in early diagnosis and curative treatment have reduced high mortality rates associated with non-small cell lung cancer. However, racial disparity in survival persists partly because Black patients receive less curative treatment than White patients. METHODS: We performed a 5-year pragmatic, trial at five cancer centers using a system-based intervention. Patients diagnosed with early stage lung cancer, aged 18-85 were eligible. Intervention components included: (1) a real-time warning system derived from electronic health records, (2) race-specific feedback to clinical teams on treatment completion rates, and (3) a nurse navigator. Consented patients were compared to retrospective and concurrent controls. The primary outcome was receipt of curative treatment. RESULTS: There were 2841 early stage lung cancer patients (16% Black) in the retrospective group and 360 (32% Black) in the intervention group. For the retrospective baseline, crude treatment rates were 78% for White patients vs 69% for Black patients (P < 0.001); difference by race was confirmed by a model adjusted for age, treatment site, cancer stage, gender, comorbid illness, and income-odds ratio (OR) 0.66 for Black patients (95% CI 0.51-0.85, P = 0.001). Within the intervention cohort, the crude rate was 96.5% for Black vs 95% for White patients (P = 0.56). Odds ratio for the adjusted analysis was 2.1 (95% CI 0.41-10.4, P = 0.39) for Black vs White patients. Between group analyses confirmed treatment parity for the intervention. CONCLUSION: A system-based intervention tested in five cancer centers reduced racial gaps and improved care for all.

Accelerated superfractionated radiotherapy with concomitant boost for locally advanced head-and-neck squamous cell carcinomas.

PURPOSE: A growing body of evidence supports the efficacy of accelerated superfractionated radiotherapy with concomitant boost for advanced head-and-neck carcinomas. This study represents a single-institution experience, performed to identify the factors influencing tumor control, survival, and toxicity. MATERIALS AND METHODS: Between 1988 and 1999, 133 patients with primary squamous cell head-and-neck carcinoma underwent accelerated superfractionated radiotherapy using a concomitant boost. The concomitant boost in this regimen was delivered using reduced fields delivered 3 times weekly in a twice-daily schedule during the final phase. The total radiation dose ranged from 64.8 Gy to 76.5 Gy (mean 71.1). Patients were evaluated in follow-up for local control and late toxicity. Multivariate analysis of treatment and patient parameters was performed to evaluate their influence on toxicity, local control, and overall survival. RESULTS: With a mean follow-up of 37 months, the actuarial overall survival rate for the entire group at 5 years was 24% and the local control rate was 57%. The tumor volume was the most significant predictor of local control, such that each 1-cm(3) increase in volume was associated with a 1% decrease in local control. For patients with tumor volumes 30 cm(3), the 5-year disease-specific survival rate was 52% and 27% (p = 0.004) and locoregional control rate was 76% and 26% (p <0.001), respectively. Seventy-six patients with a minimum of 12 months and median of 39 months toxicity follow-up were studied for late effects. None of these patients experienced Grade 4 or 5 toxicity. The actuarial rate of significant toxicity (Grade III or greater) was 32% at 5 years. Of the toxicities observed, xerostomia (19%) was the most common. Multivariate analysis revealed N stage and dose as independent predictors of Grade 3 effects. CONCLUSION: The locoregional control and survival for patients in this institutional experience compare favorably to other published reports. Tumors of the larynx had the best prognosis. Larger volume tumors were associated with significantly lower local control and survival. Significant late effects were related to dose and nodal status.

The effect of high-dose-rate brachytherapy dwell sequence on cell survival.

PURPOSE: During a high-dose-rate (HDR) brachytherapy treatment, as the source steps through different dwell positions, the dose rate at any fixed point within the implant varies, because the distance between the point and the source continually changes. The instantaneous dose rate may vary by a factor of 100 or more, in a complex dwell position sequence. Two different points which receive the same total dose may have received that dose with a very different sequence of dose rates. Any effects due to the complex changes in dose rate, including the sequence of dose delivery, are ignored. We investigated the possible effects of the sequence in which dose is delivered at two different dose rates, representative of dose rates that occur during an HDR treatment. METHODS AND MATERIALS: The target consisted of a tube containing a 1.0 cm(3) suspension of V-79 Chinese hamster cells. Two fixed source dwell positions near and far from the target, representing high and intermediate dose rates, were considered. The experiments compared the survival of V-79 cells exposed to an irradiation sequence consisting of either an HDR component followed by an intermediate-dose-rate component (H-I arm), or the reverse (I-H arm). In either case, the total dose and the dose ratio were the same, only the order in which the high- or intermediate-dose-rate components of the dose were delivered was changed. RESULTS: When the intermediate-dose-rate component was given before the HDR component, there was increased survival. All data pairs from three experiments showed greater survival for the I-H arm than the H-I arm by amounts ranging from 4% to 24%. Simple linear-quadratic models such as the Lea-Catchside model, which is invariant to time reversal of irradiation sequence, do not predict these results. CONCLUSIONS: These results suggest that targets receiving the same total dose of radiation during an HDR implant may not experience the same biological effect. This may be related to induced radioresistance or sublethal damage repair.