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Purpose: In 699 patients with locally advanced non-small-cell lung cancer (NSCLC) treated with radiation therapy as part of combined modality therapy, we compared outcomes among genotyped and ungenotyped patients and by tumor genotype status ( EGFR , KRAS , and ALK )., Patients and Methods: Genotyping was performed in 250 patients: EGFR+ (19%), KRAS+ (32%), ALK + (9%), and wild type (WT -/-/- ; 40%). Outcomes were analyzed using the Kaplan-Meier method and Cox regression., Results: With a median follow-up of 48.2 months among genotyped patients, median overall survival (OS) was significantly longer for EGFR+ and ALK+ compared with KRAS+ and WT -/-/- (55.8 months v not reached v 28.0 v 33.2 months; P = .02). There was no difference in progression-free survival (median, 15.3 v 13.7 v 13.0 v 14.5 months; P = .47) or in freedom from distant metastases by genotype (3-year estimates: 42% v 49% v 27% v 25%; P = .25). There was higher freedom from locoregional recurrence (LRR) for EGFR+ tumors and lower freedom from LRR in ALK + tumors, compared with KRAS+ and WT -/-/- tumors (3-year: 77% v 38% v 49% v 46%). In multivariable analysis, ALK+ remained associated with increased OS (HR, 0.32; 95% CI, 0.12 to 0.87; P = .03), and EGFR+ was associated with decreased LRR (HR, 0.47; 95% CI, 0.24 to 0.92; P = .03). Analysis of post-recurrence survival demonstrated that EGFR+ / ALK+ patients treated with appropriate tyrosine kinase inhibitors had higher OS compared with other groups., Conclusion: In this series of locally advanced NSCLC treated with combined modality therapy, EGFR+ and ALK+ were associated with higher OS, whereas LRR was lower in EGFR+ patients, and the risk of distant metastases was high in all subgroups. The outcomes and patterns of failure in genotypic subgroups of NSCLC from this study can inform the design of future trials integrating targeted therapies.

Surgery is potentially curative for primary nonmetastatic extremity soft tissue sarcomas. After surgery alone, patients may remain at risk for local recurrences and/or metastatic disease. To reduce the likelihood of a local relapse, the addition of radiotherapy (RT) to limb-sparing surgery may result in higher local control rates of at least 85%. Generally, it can be stated that local control after both preoperative and postoperative RT is comparable, but that preoperative RT comes with a more favorable toxicity profile after prolonged follow-up, albeit at the cost of a higher wound complication rate. Furthermore, recent data suggest that preoperative RT is more cost effective. To reduce the risk of subsequent metastatic disease, systemic chemotherapy can be introduced early during the primary management of these patients. These systemic chemotherapy regimens can also be applied both preoperatively and postoperatively. Finally, with the aim of increasing the antitumor response of perioperative RT, these agents may even be combined with RT, concurrently and sequentially. While designing new preoperative combination regimens, responses should be carefully monitored by both sophisticated radiologic and pathologic evaluations. This article reviews all these aspects, in addition to limb-sparing surgery.

Purpose: Studies have reported an association between pleural diffuse malignant mesothelioma (PDMM) and chest radiation for lymphoma. The clinicopathologic characteristics of malignant mesotheliomas arising in these patients have not been established., Patients and Methods: We studied 1,618 consecutive patients diagnosed with pleural PDMM from July 1993 to February 2008 and identified patients with a history of radiation for Hodgkin and non-Hodgkin lymphoma. We evaluated the histology in the surgical resection specimens and compared clinicopathologic features with overall survival., Results: We identified 22 patients who developed PDMM after chest radiation as part of their treatment for lymphoma (mean latency time, 21.4 years; 95% CI, 17.0 to 25.8 years). Asbestos bodies in lymphoma-associated PDMM were lower than in asbestos-associated PDMM (median count, 15 v 325 bodies, respectively; P < .001) and similar to an unexposed control group (median count, 15 v 10 bodies, respectively; P = .6). Seventeen lymphoma-associated PDMMs (77%) were epithelioid and five (23%) were biphasic. Seven PDMMs (32%) had unusual histologies (pleomorphic, myxoid, clear cell, and signet ring cell). Patients with lymphoma-associated PDMM were younger than patients with asbestos-associated PDMM (median age, 45 v 64 years, respectively; P < .001) and had a significantly longer overall survival time (median, 32.5 v 12.7 months, respectively; P = .018). In multivariate analysis, independent favorable predictors for overall survival were history of prior radiation (P = .022), female sex (P < .001), age ≤ 65 years (P = .005), cytoreductive surgery (P < .001), and epithelioid histology (P < .001)., Conclusion: Patients with lymphoma-associated PDMM are likely to have unusual histologic features, are significantly younger, and seem to have a longer overall survival compared with patients with asbestos-associated PDMM.