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Background: Consolidation durvalumab improved overall survival (OS) in locally advanced non-small cell lung cancer (LA-NSCLC) treated with chemoradiotherapy (CRT) in the PACIFIC trial; however, pneumonitis was increased with durvalumab. We sought to examine real-world outcomes with the PACIFIC paradigm, especially factors associated with pneumonitis, using a multi-institutional review. Methods: Patients with LA-NSCLC treated with CRT followed by durvalumab from January 2017-February 2019 were identified at 2 institutions. We characterized demographics, tumor factors, radiotherapy, and duration of durvalumab. We examined pneumonitis outcomes including re-challenge success, with secondary endpoints of progression-free survival (PFS) and OS. Results: Thirty-four patients were included with median follow-up of 12 months (range, 3 to 20 months); 94% had stage III disease. The cumulative grade >2 pneumonitis rate was 26.5% with 2 patients developing grade 3 pneumonitis and no grade 4/5 events. Median time to pneumonitis after RT was 2.4 months (range, 0 to 4.9 months). Pneumonitis management included median prednisone dose of 60 mg for median taper of 6 weeks with durvalumab held for median of 4.5 weeks (range, 2 to 8 weeks); 70% of pneumonitis patients received durvalumab re-challenge, with pneumonitis recurring in 14% of patients. 3-month and 6-month pneumonitis-free-survival were 76.9% and 73.6%, respectively; 9-and 12-month OS were 96% (75.1-99.8%), 86.6% (63.5-95.5%), respectively; 9-and 12-month PFS were 68% (47.5-82.5%), 48.7% (25.3-68.3%). Pneumonitis development did not significantly impact PFS or OS (P>0.05).Conclusions: Among LA-NSCLC patients treated with CRT followed by consolidation durvalumab, more than 25% developed symptomatic pneumonitis. In this small case series, pneumonitis did not appear to negatively impact survival, and durvalumab re-challenge appeared feasible after pneumonitis treatment with steroids.

Objectives. CD30+ lymphoproliferative disorder is a rare variant of cutaneous T-cell lymphoma. Sustained complete response following first-line treatments is rare. This retrospective review evaluates the response of refractory or recurrent lesions to palliative radiation therapy. Methods. The records of 6 patients with 12 lesions, treated with radiation therapy, were reviewed. All patients received previous first-line treatments. Patients with clinical and pathological evidence of symptomatic CD30+ lymphoproliferative disorder, with no history of other cutaneous T-cell lymphoma variants, and with no prior radiation therapy to the index site were included. Results. The median age of patients was 50.5 years (range, 15–83 years). Median size of the treated lesions was 2.5 cm (range, 2–7 cm). Four sites were treated with a single fraction of 750–800 cGy (n = 3) and 8 sites were treated with 4000–4500 cGy in 200–250 cGy fractions (n = 3). Radiation therapy was administered with electrons and bolus. Median follow-up was 113 months (range, 16–147 months). For all sites, there was 100% complete response with acute grade 1-2 dermatitis. Conclusions. For recurrent and symptomatic radiation-naïve CD30+ lymphoproliferative disorder lesions, palliative radiation therapy shows excellent response. A single fraction of 750–800 cGy is as effective as a multifractionated course and more convenient.

Metabolite profiling using 1 H nuclear magnetic resonance (NMR) spectroscopy was used to investigate the metabolic changes associated with deletion of the gene for the transcriptional coactivator p300 in the human colon carcinoma cell line HCT116. Multivariate statistical methods were used to distinguish between metabolite patterns that were dependent on cell growth conditions and those that were specifically associated with loss of p300 function. In the absence of serum, wild-type cells showed slower growth, which was accompanied by a marked decrease in phosphocholine concentration, which was not observed in otherwise isogenic cell lines lacking p300. In the presence of serum, several metabolites were identified as being significantly different between the two cell types, including glutamate and glutamine, a nicotinamide-related compound and glycerophosphocholine (GPC). However, in the absence of serum, these metabolites, with the exception of GPC, were not significantly different, leading us to conclude that most of these changes were context dependent. Transcript profiling, using DNA microarrays, showed changes in the levels of transcripts for several enzymes involved in choline metabolism, which might explain the change in GPC concentration. Localized in vivo 1 H NMR measurements on the tumors formed following s.c. implantation of these cells into mice showed an increase in the intensity of the peak from choline-containing compounds in the p300 À tumors. These data show that NMR-based metabolite profiling has sufficient sensitivity to identify the metabolic consequences of p300 gene deletion in tumor cells in vitro and in vivo. (Cancer Res 2006; 66(15): 7606-14)

Cisplatin-based concurrent chemoradiotherapy showed a trend toward improved recurrence-free survival survival in the definitive treatment of nonmetastatic cervical cancer. The addition of 5-FU to cisplatin did not appear to significantly impact survival or recurrence-free survival. Adenosquamous histology was associated with a higher risk of recurrence as compared with other histologic subtypes.

This study aims to report long-term clinical outcomes after Gamma Knife radiosurgery (GKRS) for intracranial grade 2 meningiomas. In this Institutional Review Board approved study, we reviewed records of all patients with grade 2 meningiomas treated with GKRS between 1998 and 2014. A total of 97 postoperative histopathologically confirmed grade 2 meningiomas in 75 patients were treated and are included in this study. After a mean follow-up of 41 months, 28 meningiomas had local recurrence (29.79%). Median time to local recurrence was 89 months (mean: 69, range: 47-168). The 3- and 5-year actuarial local control (LC) rates were 68.9 and 55.7%, respectively. The 3- and 5-year overall survival rates were 88.6 and 81.1%, respectively. There was a trend toward worse LC with tumors treated with radiation doses ≤ 13 versus > 13 Gy. There was no radiation necrosis or second malignant tumors noted in our series. This report, one of the largest GKRS series for grade 2 meningiomas, demonstrates that GKRS is a safe and effective treatment modality for patients with grade 2 meningiomas with durable tumor control and minimal toxicity. Adjuvant GKRS could be considered as a reasonable treatment approach for patients with grade 2 meningiomas.