Computed tomography-based anatomic assessment overestimates local tumor recurrence in patients with mass-like consolidation after stereotactic body radiotherapy for early-stage non-small cell lung cancer.

PURPOSE: To investigate pulmonary radiologic changes after lung stereotactic body radiotherapy (SBRT), to distinguish between mass-like fibrosis and tumor recurrence. METHODS AND MATERIALS: Eighty consecutive patients treated with 3- to 5-fraction SBRT for early-stage peripheral non-small cell lung cancer with a minimum follow-up of 12 months were reviewed. The mean biologic equivalent dose received was 150 Gy (range, 78-180 Gy). Patients were followed with serial CT imaging every 3 months. The CT appearance of consolidation was defined as diffuse or mass-like. Progressive disease on CT was defined according to Response Evaluation Criteria in Solid Tumors 1.1. Positron emission tomography (PET) CT was used as an adjunct test. Tumor recurrence was defined as a standardized uptake value equal to or greater than the pretreatment value. Biopsy was used to further assess consolidation in select patients. RESULTS: Median follow-up was 24 months (range, 12.0-36.0 months). Abnormal mass-like consolidation was identified in 44 patients (55%), whereas diffuse consolidation was identified in 12 patients (15%), at a median time from end of treatment of 10.3 months and 11.5 months, respectively. Tumor recurrence was found in 35 of 44 patients with mass-like consolidation using CT alone. Combined with PET, 10 of the 44 patients had tumor recurrence. Tumor size (hazard ratio 1.12, P=.05) and time to consolidation (hazard ratio 0.622, P=.03) were predictors for tumor recurrence. Three consecutive increases in volume and increasing volume at 12 months after treatment in mass-like consolidation were highly specific for tumor recurrence (100% and 80%, respectively). Patients with diffuse consolidation were more likely to develop grade ≥ 2 pneumonitis (odds ratio 26.5, P=.02) than those with mass-like consolidation (odds ratio 0.42, P=.07). CONCLUSION: Incorporating the kinetics of mass-like consolidation and PET to the current criteria for evaluating posttreatment response will increase the likelihood of correctly identifying patients with progressive disease after lung SBRT

Case report: response to the ERK1/2 inhibitor ulixertinib in BRAF D594G cutaneous melanoma.

Melanoma is characterized by oncogenic mutations in pathways regulating cell growth, proliferation, and metabolism. Greater than 80% of primary melanoma cases harbor aberrant activation of the mitogen-activated protein kinase kinase/extracellular-signal-regulated kinase (MEK/ERK) pathway, with oncogenic mutations in BRAF, most notably BRAF V600E, being the most common. Significant progress has been made in BRAF-mutant melanoma using BRAF and MEK inhibitors; however, non-V600 BRAF mutations remain a challenge with limited treatment options. We report the case of an individual diagnosed with stage III BRAF D594G-mutant melanoma who experienced an extraordinary response to the ERK1/2 inhibitor ulixertinib as fourth-line therapy. Ulixertinib was obtained via an intermediate expanded access protocol with unique flexibility to permit both single-agent and combination treatments, dose adjustments, breaks in treatment to undergo surgery, and long-term preventive treatment following surgical resection offering this patient the potential for curative treatment

Recurrence rates and analysis of close or positive margins in patients treated without re-excision before radiation for breast cancer.

PURPOSE: This study examines the risk of local recurrence in a group of patients accepted for radiation therapy after breast-conserving surgery despite having a close or positive resection margin. METHODS AND MATERIALS: Two hundred patients with early-stage breast cancer were treated by radiation with a nonnegative margin \u3c or =2 mm from January 1974 to September 2001. The median age was 61 years. Margins were positive in 29% and close (\u3c or =2 mm) in 71%. The median dose was 64 to 66 Gy. The median follow up was 5.9 years. RESULTS: The number of resection margins close or positive was 1 in 73% of patients, 2 in 14%, 3 in 1%, and unknown in 12%. The margin location was 23% anterior, 24% posterior, 12% medial, 12% lateral, 17% superior, and 12% inferior. Reasons for not reexcising were advanced age/comorbidities in 7%, anterior location under skin in 25%, posterior location to muscle in 15%, focal involvement in 13%, no extensive intraductal component in 5%, surgeon refusal in 15%, and patient refusal in 20%. There was a strong association between an anterior or posterior margin location and the rationale of no additional breast tissue at the margin to reexcise before radiation. The risk of local recurrence at 5 and 10 years was 3% and 5%, respectively. CONCLUSIONS: Further research of close and positive margins is needed to validate features identified in this series, particularly nonbreast tissue anatomic margins, that are associated with low risks of local recurrence after radiation

Fibroblast Growth Factor Receptor 3 Amplified Metastatic Melanoma Treated With Erdafitinib.

The treatment of metastatic melanoma has changed dramatically in the last decade with the introduction of immunotherapy and targeted therapy. A futile disease in the past is now treated with various options, resulting in improvement in progression-free and overall survivals, along with improvement in the quality of life. Having said that, the majority of patients with metastatic melanoma eventually succumb to the disease. Molecular profiling of each tumor in the advanced stage is standard of care now, as this would lead to individualized treatment options for each patient. Here, we present a rare case of fibroblast growth factor receptor 3 (FGFR 3) amplified metastatic melanoma, treated rather unconventionally with FGFR 3 inhibitor erdafitinib

Dramatic Response to Concurrent Anti-PD-1 Therapy and Radiation in Resistant Tumors with Sarcomatoid Differentiation.

A substantial fraction of patients demonstrate resistance to immune checkpoint inhibitors, which limits their use. Use of radiation concurrently with checkpoint inhibitors has been shown to boost immune responsiveness, resulting in significant tumor regression in patients with metastatic melanoma. However, it is unknown whether radiation could play a role in reversing the inherent resistance to checkpoint inhibition in certain tumor types. Most trials testing this concurrent approach exclude such modestly responsive tumors and pursue checkpoint inhibition using anti-cytotoxic T-lymphocyte-associated protein 4 antibody (anti-CTLA-4, ipilimumab). The efficacy of anti-programmed-death-1 (anti-PD-1) therapy when used concurrently with radiation is less known but remains an attractive option due to less autoimmune toxicity compared with CTLA-4 inhibition. In this first reported experience, we have safely and effectively combined anti-PD-1 therapy (nivolumab) concurrently with radiation to treat two patients with relapsed sarcomatoid renal carcinoma and heavily pretreated pleomorphic sarcoma. Both patients experienced a dramatic response that was durable

Quantifying the reproducibility of heart position during treatment and corresponding delivered heart dose in voluntary deep inhalation breath hold for left breast cancer patients treated with external beam radiotherapy.

PURPOSE: Voluntary deep inhalation breath hold (VDIBH) reduces heart dose during left breast irradiation. We present results of the first study performed to quantify reproducibility of breath hold using bony anatomy, heart position, and heart dose for VDIBH patients at treatment table. METHODS AND MATERIALS: Data from 10 left breast cancer patients undergoing VDIBH whole-breast irradiation were analyzed. Two computed tomography (CT) scans, free breathing (FB) and VDIBH, were acquired to compare dose to critical structures. Pretreatment weekly kV orthogonal images and tangential ports were acquired. The displacement difference from spinal cord to sternum across the isocenter between coregistered planning Digitally Reconstructed Radiographs (DRRs) and kV imaging of bony thorax is a measure of breath hold reproducibility. The difference between bony coregistration and heart coregistration was the measured heart shift if the patient is aligned to bony anatomy. RESULTS: Percentage of dose reductions from FB to VDIBH: mean heart dose (48%, SD 19%, p = 0.002), mean LAD dose (43%, SD 19%, p = 0.008), and maximum left anterior descending (LAD) dose (60%, SD 22%, p = 0.008). Average breath hold reproducibility using bony anatomy across the isocenter along the anteroposterior (AP) plane from planning to treatment is 1 (range, 0-3; SD, 1) mm. Average heart shifts with respect to bony anatomy between different breath holds are 2 ± 3 mm inferior, 1 ± 2 mm right, and 1 ± 3 mm posterior. Percentage dose changes from planning to delivery: mean heart dose (7%, SD 6%); mean LAD dose, ((9%, SD 7%)S, and maximum LAD dose, (11%, SD 11%) SD 11%, p = 0.008). CONCLUSION: We observed excellent three-dimensional bony registration between planning and pretreatment imaging. Reduced delivered dose to heart and LAD is maintained throughout VDIBH treatment