Objectives: To evaluate the palliative benefits of image-guided thermal ablation for the treatment of painful tumors affecting the chest wall. Methods: Thirty-nine patients, median age 65 years, underwent percutaneous thermal ablation of 44 chest wall masses. Thirty-eight radiofrequency ablations (RFAs), 3 microwave ablations (MWAs), and 3 cryoablations were performed. Subjective pain reports at 1 week and 1 month postablation were scored from 0 to 4 based on a standard Likert pain relief scale, with 2 or higher representing clinically significant pain relief. Results: Patients were followed for a median of 6 months. Overall, 31 of 44 procedures (70.5%) resulted in significant pain relief. Improvement followed 15 of 15 (100%) of ablations that were performed within 90 days of treatment with palliative external-beam radiation therapy (XRT), compared with 16 of 29 (55.2%) of the remaining procedures. Mean pain relief score at 1 month was 3.86 for the 15 combined procedures versus 1.96 for the 29 remaining procedures (P < 0.001). Local pain recurred after 5 of 31 positive responses (16.1%). Median survival was 11.2 ± 2.3 months for patients with significant pain relief and 4.3 ± 1.4 months for nonresponders (P < 0.001). Adverse events included a transient symptom “flare” (n = 5, 11.4%) and the exacerbation of a preexisting brachial plexopathy. Conclusions: Thermal ablation results in significant pain relief for the majority of patients and shows evidence of synergistic benefit when temporally combined with XRT. This minimally invasive technique appears to be a safe and durable alternative for the palliation of chest wall masses.
Selpercatinib and pralsetinib are RET inhibitors with substantial activity in advanced RET-rearranged NSCLC. We present a case of pralsetinib-related pneumonitis and leptomeningeal and brain metastases progression during treatment suspension for pneumonitis. During recovery, selpercatinib administration led to rapid neurologic response and complete intracranial response and allowed pneumonitis resolution. This case supports the safety of selpercatinib in patients with pneumonitis on pralsetinib and highlights its marked efficacy in leptomeningeal disease.
The authors added detailed treatment data which may be valuable information for readers to their study "Dabrafenib plus trametinib versus anti-PD-1 monotherapy as adjuvant therapy in BRAF V600-mutant stage III melanoma after definitive surgery: a multicenter, retrospective cohort study". "In our study, amongst 205 PD-1 treated patients, there were 106 treated with nivolumab, 81 with pembrolizumab, and 18 with toripalimab. We performed an ad hoc analysis using nivolumab as the reference, and no differences in terms of either RFS and OS were observed between different therapeutic agents in multivariate analysis adjusting for age, sex, ethnicity, BRAF mutation subtype, AJCC staging, SLNB, CLND, and adjuvant radiotherapy statuses: RFS: pembrolizumab: HR 0.90 (95% CI, 0.56–1.43, P = 0.65), toripalimab: HR 0.63 (95% CI, 0.22–1.83, P = 0.40). OS: pembrolizumab: HR 0.80 (95% CI, 0.35–1.82, P = 0.59), toripalimab: HR 0.34 (95% CI, 0.07–1.57, P = 0.17). The median on-treatment duration of different treatments: nivolumab 10.5 months, pembrolizumab 11.4 months, and toripalimab 11.0 months; all close to 12 months, with a median duration difference of <1 month, thus considered clinically insignificant. This additional information does not affect any of the findings and conclusions in the original paper. Dabrafenib plus trametinib versus anti-PD-1 monotherapy as adjuvant therapy in BRAF V600-mutant stage III melanoma after definitive surgery: a multicenter, retrospective cohort studyIn patients with stage III BRAF V600-mutant melanoma post definitive surgery, D/T yielded better RFS than PD-1, with higher transient but lower persistent toxicity, and comparable OS. D/T seems to provide a better outcome compared with PD-1, but a longer follow-up and ideally a large prospective trial are needed. Full-Text PDF Open Access
Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer, but a comprehensive description of its genomic landscape is lacking. We report the whole genome sequencing of 778 ccRCC patients enrolled in the 100,000 Genomes Project, providing for a detailed description of the somatic mutational landscape of ccRCC. We identify candidate driver genes, which as well as emphasising the major role of epigenetic regulation in ccRCC highlight additional biological pathways extending opportunities for therapeutic interventions. Genomic characterisation identified patients with divergent clinical outcome; higher number of structural copy number alterations associated with poorer prognosis, whereas VHL mutations were independently associated with a better prognosis. The observations that higher T-cell infiltration is associated with better overall survival and that genetically predicted immune evasion is not common supports the rationale for immunotherapy. These findings should inform personalised surveillance and treatment strategies for ccRCC patients.
Abstract Despite initial responses to hormone treatment, metastatic prostate cancer invariably evolves to a lethal state. To characterize the intra-patient evolutionary relationships of metastases that evade treatment, we perform genome-wide copy number profiling and bespoke approaches targeting the androgen receptor (AR) on 167 metastatic regions from 11 organs harvested post-mortem from 10 men who died from prostate cancer. We identify diverse and patient-unique alterations clustering around the AR in metastases from every patient with evidence of independent acquisition of related genomic changes within an individual and, in some patients, the co-existence of AR -neutral clones. Using the genomic boundaries of pan-autosome copy number changes, we confirm a common clone of origin across metastases and diagnostic biopsies, and identified in individual patients, clusters of metastases occupied by dominant clones with diverged autosomal copy number alterations. These autosome-defined clusters are characterized by cluster-specific AR gene architectures, and in two index cases are topologically more congruent than by chance ( p -values 3.07 × 10 −8 and 6.4 × 10 −4 ). Integration with anatomical sites suggests patterns of spread and points of genomic divergence. Here, we show that copy number boundaries identify treatment-selected clones with putatively distinct lethal trajectories.
To retrospectively evaluate long-term survival, local tumor progression, and complication rates for all percutaneous computed tomographic (CT)-guided lung tumor radiofrequency (RF) ablations performed at a tertiary care cancer hospital in patients who refused or who were not candidates for surgery.This HIPAA-compliant study was approved by the institutional review board; informed consent was waived. Between 1998 and 2005, 153 consecutive patients (mean age, 68.5 years; range, 17-94 years) with 189 primary or metastatic medically inoperable lung cancers underwent percutaneous fluoroscopic CT-guided RF ablation. Clinical outcomes were compiled on the basis of review of medical records, imaging follow-up reports, and any biopsy-proved residual or recurrent disease (when available). Kaplan-Meier method was used to estimate overall survival and disease-free survival (progression) as a function of time since RF ablation. Comparisons between survival functions were performed by using the log-rank statistic; P < .05 was considered to indicate a significant difference.The overall 1-, 2-, 3-, 4-, and 5-year survival rates, respectively, for stage I non-small cell lung cancer were 78%, 57%, 36%, 27%, and 27%; rates for colorectal pulmonary metastasis were 87%, 78%, 57%, 57%, and 57%. The 1-, 2-, 3-, 4-, and 5-year local tumor progression-free rates, respectively, were 83%, 64%, 57%, 47%, and 47% for tumors 3 cm or smaller and 45%, 25%, 25%, 25%, and 25% for tumors larger than 3 cm. The difference between the survival curves associated with large (>3 cm) and small (< or =3 cm) tumors was significant (P < .002). The overall pneumothorax rate was 28.4% (52 of 183 ablation sessions), with a 9.8% (18 of 183 ablation sessions) chest tube insertion rate. The overall 30-day mortality rate was 3.9% (six of 153 patients), with a 2.6% (four of 153 patients) procedure-specific 30-day mortality rate.Lung RF ablation appears to be safe and linked with promising long-term survival and local tumor progression outcomes, especially given the patient population treated.
At the outset of the pandemic, SARS-CoV-2 was thought to present simply as persistent cough and fever. However, with time, the medical community noted a myriad of associated symptoms well-described in the literature. Medical complications were particularly common in elderly populations and many early publications described pneumonia, organ failure, acute respiratory distress syndrome, hypercoagulability/microthrombosis and superimposed bacterial/viral infections. There is, however, a lack of literature describing surgical complications of COVID-19 and as such little knowledge regarding safe surgical interventions. This case describes the presentation/management of a patient who developed COVID-19-associated necrotising pneumonia. Video-assisted thoracoscopy lobectomy was performed following CT demonstration of necrotising pneumonia. Pathological evaluation of the surgical resection specimen demonstrated the microarchitecture of a severely diseased COVID-19 lung-fibrosis. This case demonstrates the safe management of a necrotic lung using a minimal access approach in the context of COVID-19 infection.
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