The Color of Successtells of the astonishing transformation of Asians in the United States from the "yellow peril" to "model minorities"--peoples distinct from the white majority but lauded as ...well-assimilated, upwardly mobile, and exemplars of traditional family values--in the middle decades of the twentieth century. As Ellen Wu shows, liberals argued for the acceptance of these immigrant communities into the national fold, charging that the failure of America to live in accordance with its democratic ideals endangered the country's aspirations to world leadership.
Weaving together myriad perspectives, Wu provides an unprecedented view of racial reform and the contradictions of national belonging in the civil rights era. She highlights the contests for power and authority within Japanese and Chinese America alongside the designs of those external to these populations, including government officials, social scientists, journalists, and others. And she demonstrates that the invention of the model minority took place in multiple arenas, such as battles over zoot suiters leaving wartime internment camps, the juvenile delinquency panic of the 1950s, Hawaii statehood, and the African American freedom movement. Together, these illuminate the impact of foreign relations on the domestic racial order and how the nation accepted Asians as legitimate citizens while continuing to perceive them as indelible outsiders.
By charting the emergence of the model minority stereotype,The Color of Successreveals that this far-reaching, politically charged process continues to have profound implications for how Americans understand race, opportunity, and nationhood.
Stereotactic body radiation therapy (SBRT) in central lung tumors has been associated with higher rates of severe toxicity. We sought to evaluate toxicity and local control in a large cohort and to ...identify predictive dosimetric parameters.
We identified patients who received SBRT for central tumors according to either of 2 definitions. Local failure (LF) was estimated using a competing risks model, and multivariate analysis (MVA) was used to assess factors associated with LF. We reviewed patient toxicity and applied Cox proportional hazard analysis and log-rank tests to assess whether dose-volume metrics of normal structures correlated with pulmonary toxicity.
One hundred twenty-five patients received SBRT for non-small cell lung cancer (n=103) or metastatic lesions (n=22), using intensity modulated radiation therapy. The most common dose was 45 Gy in 5 fractions. Median follow-up was 17.4 months. Incidence of toxicity ≥ grade 3 was 8.0%, including 5.6% pulmonary toxicity. Sixteen patients (12.8%) experienced esophageal toxicity ≥ grade 2, including 50% of patients in whom PTV overlapped the esophagus. There were 2 treatment-related deaths. Among patients receiving biologically effective dose (BED) ≥80 Gy (n=108), 2-year LF was 21%. On MVA, gross tumor volume (GTV) was significantly associated with LF. None of the studied dose-volume metrics of the lungs, heart, proximal bronchial tree (PBT), or 2 cm expansion of the PBT ("no-fly-zone" NFZ) correlated with pulmonary toxicity ≥grade 2. There were no differences in pulmonary toxicity between central tumors located inside the NFZ and those outside the NFZ but with planning target volume (PTV) intersecting the mediastinum.
Using moderate doses, SBRT for central lung tumors achieves acceptable local control with low rates of severe toxicity. Dosimetric analysis showed no significant correlation between dose to the lungs, heart, or NFZ and severe pulmonary toxicity. Esophageal toxicity may be an underappreciated risk, particularly when PTV overlaps the esophagus.
We previously reported our technique for delivering intensity modulated radiation therapy (IMRT) to the entire pleura while attempting to spare the lung in patients with malignant pleural ...mesothelioma (MPM). Herein, we report a detailed pattern-of-failure analysis in patients with MPM who were unresectable or underwent pleurectomy/decortication (P/D), uniformly treated with hemithoracic pleural IMRT.
Sixty-seven patients with MPM were treated with definitive or adjuvant hemithoracic pleural IMRT between November 2004 and May 2013. Pretreatment imaging, treatment plans, and posttreatment imaging were retrospectively reviewed to determine failure location(s). Failures were categorized as in-field (within the 90% isodose line), marginal (<90% and ≥50% isodose lines), out-of-field (outside the 50% isodose line), or distant.
The median follow-up was 24 months from diagnosis and the median time to in-field local failure from the end of RT was 10 months. Forty-three in-field local failures (64%) were found with a 1- and 2-year actuarial failure rate of 56% and 74%, respectively. For patients who underwent P/D versus those who received a partial pleurectomy or were deemed unresectable, the median time to in-field local failure was 14 months versus 6 months, respectively, with 1- and 2-year actuarial in-field local failure rates of 43% and 60% versus 66% and 83%, respectively (P=.03). There were 13 marginal failures (19%). Five of the marginal failures (38%) were located within the costomediastinal recess. Marginal failures decreased with increasing institutional experience (P=.04). Twenty-five patients (37%) had out-of-field failures. Distant failures occurred in 32 patients (48%).
After hemithoracic pleural IMRT, local failure remains the dominant form of failure pattern. Patients treated with adjuvant hemithoracic pleural IMRT after P/D experience a significantly longer time to local and distant failure than patients treated with definitive pleural IMRT. Increasing experience and improvement in target delineation minimize the incidence of avoidable marginal failures.
Stereotactic body radiotherapy (SBRT) has been adopted as the standard of care for inoperable early-stage non-small cell lung cancer (NSCLC), with local control rates consistently >90%. However, data ...directly comparing the outcomes of SBRT with those of conventionally fractionated radiotherapy (CONV) is lacking.
Between 1990 and 2013, 497 patients (525 lesions) with early-stage NSCLC (T1-T2N0M0) were treated with CONV (n = 127) or SBRT (n = 398). In this retrospective analysis, five endpoints were compared, with and without adjusting for clinical and dosimetric factors. Competing risks analysis was performed to estimate and compare the cumulative incidence of local failure (LF), nodal failure (NF), distant failure (DF) and disease progression. Overall survival (OS) was estimated by the Kaplan-Meier method and compared by the Cox regression model. Propensity score (PS) matched analysis was performed based on seven patient and clinical variables: age, gender, Karnofsky performance status (KPS), histology, T stage, biologically equivalent dose (BED), and history of smoking.
The median dose delivered for CONV was 75.6 Gy in 1.8-2.0 Gy fractions (range 60-90 Gy; median BED = 89.20 Gy) and for SBRT 48 Gy in four fractions (45-60 Gy in three to five fractions; median BED = 105.60 Gy). Median follow-up was 24.4 months, and 3-year LF rates were 34.1% with CONV and 13.6% with SBRT (p < .001). Three-year OS rates were 38.9 and 53.1%, respectively (p = .018). PS matching showed a significant improvement of OS (p = .0497) for SBRT. T stage was the only variable correlating with all five endpoints.
SBRT compared to CONV is associated with improved LF rates and OS. Our data supports the continued use and expansion of SBRT as the standard of care treatment for inoperable early-stage NSCLC.
Stereotactic body radiation therapy (SBRT) is associated with excess toxicity following treatment of central lung tumors. Risk-adapted fractionation appears to have mitigated this risk, but it ...remains unclear whether SBRT is safe for all tumors within the central lung zone, especially those abutting the proximal bronchial tree (PBT). We investigated the dependence of toxicity on tumor proximity to PBT and whether tumors abutting the PBT had greater toxicity than other central lung tumors after SBRT.
A total of 108 patients receiving SBRT for central lung tumors were reviewed. Patients were classified based on closest distance from tumor to PBT. Primary endpoint was SBRT-related death. Secondary endpoints were overall survival, local control, and grade 3+ pulmonary adverse events. We compared tumors abutting the PBT to nonabutting and those ≤1 cm and >1 cm from PBT.
Median follow-up was 22.7 months. Median distance from tumor to PBT was 1.78 cm. Eighty-eight tumors were primary lung and 20 were recurrent or metastatic; 23% of tumors were adenocarcinoma and 71% squamous cell. Median age was 77.5 years. Median dose was 4500 cGy in 5 fractions prescribed to the 100% isodose line. Eighteen patients had tumors abutting the PBT, 4 of whom experienced SBRT-related death. No other patients experienced death attributed to SBRT. Risk of SBRT-related death was significantly higher for tumors abutting the PBT compared with nonabutting tumors (P < .001). Two patients with SBRT-related death received anti-vascular endothelial growth factor therapy and experienced pulmonary hemorrhage. Patients with tumors ≤1 cm from PBT had significantly more grade 3+ events than those with tumors >1cm from PBT (P = .014).
Even with risk-adapted fractionation, tumors abutting PBT are associated with a significant and differential risk of SBRT-related toxicity and death. SBRT should be used with particular caution in central-abutting tumors, especially in the context of anti-vascular endothelial growth factor therapy.
We conducted a two-center phase II study to determine the safety of hemithoracic intensity-modulated pleural radiation therapy (IMPRINT) after chemotherapy and pleurectomy-decortication (P/D) as part ...of a multimodality lung-sparing treatment.
Patients received up to four cycles of pemetrexed plus platinum. If feasible, P/D was performed. Hemithoracic IMPRINT was administered to a planned dose of 50.4 Gy in 28 fractions. The primary end point was the incidence of grade 3 or greater radiation pneumonitis (RP).
A total of 45 patients were enrolled; 18 were not evaluable (because of disease progression before radiation therapy RT, n = 9; refusal of surgery or RT, n = 5; extrapleural pneumonectomy at time of surgery, n = 2; or chemotherapy complications, n = 2). A total of 26 patients received pemetrexed plus cisplatin, 18 received pemetrexed plus carboplatin, and four received a combination. Thirteen patients (28.9%) had a partial response, 15 patients (33.3%) experienced disease progression, one patient died during chemotherapy, and all others had stable disease. Eight patients underwent P/D or an extended P/D, and 13 underwent a partial P/D. A total of 27 patients started IMPRINT (median dose, 46.8 Gy; range, 28.8 to 50.4 Gy) and were evaluable for the primary end point (median follow-up, 21.6 months). Six patients experienced grade 2 RP, and two patients experienced grade 3 RP; all recovered after corticosteroid initiation. No grade 4 or 5 radiation-related toxicities were observed. The median progression-free survival and overall survival (OS) were 12.4 and 23.7 months, respectively; the 2-year OS was 59% in patients with resectable tumors and was 25% in patients with unresectable tumors.
Hemithoracic IMPRINT for malignant pleural mesothelioma (MPM) is safe and has an acceptable rate of RP. Its incorporation with chemotherapy and P/D forms a new lung-sparing treatment paradigm for patients with locally advanced MPM.
To assess intrafractional positional variations of pancreatic tumors using 4-dimensional computed tomography (4D-CT), their impact on gross tumor volume (GTV) coverage, the reliability of biliary ...stent, fiducial seeds, and the real-time position management (RPM) external marker as tumor surrogates for setup of respiratory gated treatment, and to build a correlative model of tumor motion.
We analyzed the respiration-correlated 4D-CT images acquired during simulation of 36 patients with either a biliary stent (n=16) or implanted fiducials (n=20) who were treated with RPM respiratory gated intensity modulated radiation therapy for locally advanced pancreatic cancer. Respiratory displacement relative to end-exhalation was measured for the GTV, the biliary stent, or fiducial seeds, and the RPM marker. The results were compared between the full respiratory cycle and the gating interval. Linear mixed model was used to assess the correlation of GTV motion with the potential surrogate markers.
The average ± SD GTV excursions were 0.3 ± 0.2 cm in the left-right direction, 0.6 ± 0.3 cm in the anterior-posterior direction, and 1.3 ± 0.7 cm in the superior-inferior direction. Gating around end-exhalation reduced GTV motion by 46% to 60%. D95% was at least the prescribed 56 Gy in 76% of patients. GTV displacement was associated with the RPM marker, the biliary stent, and the fiducial seeds. The correlation was better with fiducial seeds and with biliary stent.
Respiratory gating reduced the margin necessary for radiation therapy for pancreatic tumors. GTV motion was well correlated with biliary stent or fiducial seed displacements, validating their use as surrogates for daily assessment of GTV position during treatment. A patient-specific internal target volume based on 4D-CT is recommended both for gated and not-gated treatment; otherwise, our model can be used to predict the degree of GTV motion.
Introduction
Durvalumab after concurrent chemoradiation (cCRT) is now standard of care for unresected stage III non–small cell lung cancer (NSCLC). However, there is limited data on radiation ...pneumonitis (RP) with this regimen. Therefore, we assessed RP and evaluated previously validated toxicity models in predicting for RP in patients treated with cCRT and durvalumab.
Methods
Patients treated with cCRT and ≥ 1 dose of durvalumab were evaluated to identify cases of ≥ grade 2 RP. The validity of previously published RP models was assessed in this cohort as well a reference cohort treated with cCRT alone. The timing and incidence of RP was compared between cohorts.
Results
In total, 11 (18%) of the 62 patients who received cCRT and durvalumab developed ≥ grade 2 RP a median of 3.4 months after cCRT. The onset of RP among patients treated with cCRT and durvalumab was significantly longer vs the reference cohort (3.4 vs 2.1 months; P = .01). Numerically more patients treated with cCRT and durvalumab developed RP than patients in the reference cohort (18% vs 9%, P = .09). Among patients treated with cCRT and durvalumab, 82% (n = 9) were responsive to treatment with high‐dose glucocorticoids. Previously published RP models widely underestimated the rate of RP in patients treated with cCRT and durvalumab AUC ~ 0.50; p(Hosmer‐Lemeshow): 0.98‐1.00.
Conclusions
Our data suggest a delayed onset of RP in patients treated with cCRT and durvalumab vs cCRT alone, and for RP to develop in a greater number of patients treated with cCRT and durvalumab. Previously published RP models significantly underestimate the rate of symptomatic RP among patients treated with cCRT and durvalumab.
Radiation pneumonitis (RP) is a significant toxicity of thoracic radiation, yet little is known regarding RP in lung cancer patients treated with definitive chemoradiation (cCRT) and durvalumab. We found patients treated with cCRT and durvalumab to have a significantly later onset of RP and a greater frequency of RP compared to patients treated with cCRT alone, we also found previously published toxicity models to be unsuccessful in predicting for RP among patients treated with cCRT and durvalumab.
Highlights • The prognostic value of SUVmax before SBRT has not been consistently demonstrated. • An SUVmax cutpoint of 3.0 is optimal for stratifying SBRT patients by survival. • Pre-treatment ...SUVmax >3.0 is associated with worse survival in SBRT patients. • Higher SUVmax was also associated with both local and distant failure after SBRT.
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