Unforeseen Computed Tomography Resimulation for Initial Radiation Planning: Associated Factors and Clinical Impact

Purpose: Repeat computed tomography (CT) simulation is problematic because of additional expense of clinic resources, patient inconvenience, additional radiation exposure, and treatment delay. We investigated the factors and clinical impact of unplanned CT resimulations in our network. Methods and Materials: We used the billing records of 18,170 patients treated at 5 clinics. A total of 213 patients were resimulated before their first treatment. The disease site, location, use of 4- dimensional CT (4DCT), contrast, image fusion, and cause for resimulation were recorded. Odds ratios determined statistical significance. Results: Our total rate of resimulation was 1.2%. Anal/colorectal (P \u3c .001) and head and neck (P \u3c .001) disease sites had higher rates of resimulation. Brain (P Z .001) and lung/thorax (P Z .008) had lower rates of resimulation. The most common causes for resimulation were setup change (11.7%), change in patient anatomy (9.8%), and rectal filling (8.5%). The resimulation rate for 4DCTs was 3.03% compared with 1.0% for non-4DCTs (P \u3c .001). Median time between simulations was 7 days. Conclusions: The most common sites for resimulation were anal/colorectal and head and neck, largely because of change in setup or changes in anatomy. The 4DCT technique correlated with higher resimulation rates. The resimulation rate was 1.2%, and median treatment delay was 7 days. Further studies are warranted to limit the rate of resimulation

CDK4/6 inhibition triggers anti-tumor immunity

Cyclin-dependent kinases 4 and 6 (CDK4/6) are fundamental drivers of the cell cycle and are required for the initiation and progression of various malignancies1,2. Pharmacologic inhibitors of CDK4/6 have shown significant activity against several solid tumors3,4. Their primary mechanism of action is thought to be the inhibition of phosphorylation of the retinoblastoma (RB) tumor suppressor, inducing G1 cell cycle arrest in tumor cells5. Here, we use murine models of breast carcinoma and other solid tumors to show that selective CDK4/6 inhibitors not only induce tumor cell cycle arrest, but also promote anti-tumor immunity. We confirm this phenomenon through transcriptomic analysis of serial biopsies from a clinical trial of CDK4/6 inhibitor treatment for breast cancer. The enhanced anti-tumor immune response has two underpinnings. First, CDK4/6 inhibitors activate tumor cell expression of endogenous retroviral elements, thus increasing intracellular levels of double-stranded RNA. This in turn stimulates production of type III interferons and hence enhances tumor antigen presentation. Second, CDK4/6 inhibitors markedly suppress the proliferation of regulatory T cells (Tregs). Mechanistically, the effects of CDK4/6 inhibitors on both tumor cells and Tregs are associated with reduced activity of the E2F target, DNA methyltransferase 1. Ultimately, these events promote cytotoxic T cell-mediated clearance of tumor cells, which is further enhanced by the addition of immune checkpoint blockade. Our findings indicate that CDK4/6 inhibitors increase tumor immunogenicity and provide rationale for new combination regimens comprising CDK4/6 inhibitors and immunotherapies as anti-cancer treatment

Global assessment of marine plastic exposure risk for oceanic birds

Plastic pollution is distributed patchily around the world’s oceans. Likewise, marine organisms that are vulnerable to plastic ingestion or entanglement have uneven distributions. Understanding where wildlife encounters plastic is crucial for targeting research and mitigation. Oceanic seabirds, particularly petrels, frequently ingest plastic, are highly threatened, and cover vast distances during foraging and migration. However, the spatial overlap between petrels and plastics is poorly understood. Here we combine marine plastic density estimates with individual movement data for 7137 birds of 77 petrel species to estimate relative exposure risk. We identify high exposure risk areas in the Mediterranean and Black seas, and the northeast Pacific, northwest Pacific, South Atlantic and southwest Indian oceans. Plastic exposure risk varies greatly among species and populations, and between breeding and non-breeding seasons. Exposure risk is disproportionately high for Threatened species. Outside the Mediterranean and Black seas, exposure risk is highest in the high seas and Exclusive Economic Zones (EEZs) of the USA, Japan, and the UK. Birds generally had higher plastic exposure risk outside the EEZ of the country where they breed. We identify conservation and research priorities, and highlight that international collaboration is key to addressing the impacts of marine plastic on wide-ranging species

Global assessment of marine plastic exposure risk for oceanic birds

Plastic pollution is distributed patchily around the world’s oceans. Likewise, marine organisms that are vulnerable to plastic ingestion or entanglement have uneven distributions. Understanding where wildlife encounters plastic is crucial for targeting research and mitigation. Oceanic seabirds, particularly petrels, frequently ingest plastic, are highly threatened, and cover vast distances during foraging and migration. However, the spatial overlap between petrels and plastics is poorly understood. Here we combine marine plastic density estimates with individual movement data for 7137 birds of 77 petrel species to estimate relative exposure risk. We identify high exposure risk areas in the Mediterranean and Black seas, and the northeast Pacific, northwest Pacific, South Atlantic and southwest Indian oceans. Plastic exposure risk varies greatly among species and populations, and between breeding and non-breeding seasons. Exposure risk is disproportionately high for Threatened species. Outside the Mediterranean and Black seas, exposure risk is highest in the high seas and Exclusive Economic Zones (EEZs) of the USA, Japan, and the UK. Birds generally had higher plastic exposure risk outside the EEZ of the country where they breed. We identify conservation and research priorities, and highlight that international collaboration is key to addressing the impacts of marine plastic on wide-ranging species

Unforeseen Computed Tomography Resimulation for Initial Radiation Planning: Associated Factors and Clinical Impact.

PURPOSE: Repeat computed tomography (CT) simulation is problematic because of additional expense of clinic resources, patient inconvenience, additional radiation exposure, and treatment delay. We investigated the factors and clinical impact of unplanned CT resimulations in our network. METHODS AND MATERIALS: We used the billing records of 18,170 patients treated at 5 clinics. A total of 213 patients were resimulated before their first treatment. The disease site, location, use of 4-dimensional CT (4DCT), contrast, image fusion, and cause for resimulation were recorded. Odds ratios determined statistical significance. RESULTS: Our total rate of resimulation was 1.2%. Anal/colorectal ( CONCLUSIONS: The most common sites for resimulation were anal/colorectal and head and neck, largely because of change in setup or changes in anatomy. The 4DCT technique correlated with higher resimulation rates. The resimulation rate was 1.2%, and median treatment delay was 7 days. Further studies are warranted to limit the rate of resimulation

Management trends and outcomes of breast angiosarcoma: Is breast conservation feasible?

We queried the National Cancer Database for nonmetastatic breast angiosarcoma, yielding 808 patients (202 de novo, 606 secondary). The median survival was 53.7 months. Secondary tumors were more likely to undergo mastectomy than de novo lesions (OR = 3.99, P \u3c 0.001). Treatments included lumpectomy (10%), lumpectomy/radiation (3%), mastectomy alone (73%), or mastectomy/radiation (14%), with no difference in survival (P = 0.68). Lumpectomy correlated with positive margin rate (OR 3.29), which was a predictor for death (HR = 2.37, P \u3c 0.01), along with older age, higher comorbidity scores, size \u3e5 cm, and high-grade disease (P \u3c 0.05). While breast angiosarcoma is usually treated with mastectomy, lumpectomy may be feasible for well-selected tumors

Patterns of care and outcomes in small cell carcinoma of the prostate: A national cancer database analysis

BACKGROUND: Small cell carcinoma (SCC) of the prostate is a rare, aggressive disease. Evidence is limited; however, the current standard of care is chemotherapy. The benefit of local treatment modalities is unknown. METHODS: We queried the National Cancer Database identifying all SCC/neuroendocrine cases of the prostate, excluding those with unknown nodal or metastatic status, unknown treatment, or those not receiving chemotherapy. Overall survival (OS) was calculated using Kaplan-Meier curves. Multivariable Cox proportional hazards model was used to identify factors associated with survival. A further subgroup analysis was performed on the utility of local therapy on survival in the nonmetastatic setting. RESULTS: Our final cohort included 657 patients with a median age of 68. Most patients had positive lymph nodes (60.1%) and metastatic disease (70.0%). Median survival was 12 months (95% confidence interval [95% CI], 11.1-13.3 months) with a median follow-up of 11.8 months. Metastatic disease, age greater than or equal to 70, omission of androgen deprivation therapy (ADT), and lower income (P \u3c .05 for all) were all associated with reduced OS. Patients with prostate-specific antigen (PSA) greater than or equal to 33 ng/mL and those receiving ADT had better survival (P \u3c .05). Those with nonmetastatic disease were more likely to undergo prostatectomy and/or prostatic/pelvic radiation (P \u3c .0001). Prostatic/pelvic radiation in the nonmetastatic setting was associated with longer survival (P = .02). Though well powered, our study is limited by the selection bias inherent to all observational studies, despite the statistical methods utilized to reduce this effect. CONCLUSIONS: Although chemotherapy is the mainstay of treatment, radiation to the prostate/pelvis may be beneficial in the nonmetastatic setting. In addition to chemotherapy, ADT may benefit patients with an elevated PSA

Patterns of care and outcomes in small cell carcinoma of the prostate: A national cancer database analysis.

BACKGROUND: Small cell carcinoma (SCC) of the prostate is a rare, aggressive disease. Evidence is limited; however, the current standard of care is chemotherapy. The benefit of local treatment modalities is unknown. METHODS: We queried the National Cancer Database identifying all SCC/neuroendocrine cases of the prostate, excluding those with unknown nodal or metastatic status, unknown treatment, or those not receiving chemotherapy. Overall survival (OS) was calculated using Kaplan-Meier curves. Multivariable Cox proportional hazards model was used to identify factors associated with survival. A further subgroup analysis was performed on the utility of local therapy on survival in the nonmetastatic setting. RESULTS: Our final cohort included 657 patients with a median age of 68. Most patients had positive lymph nodes (60.1%) and metastatic disease (70.0%). Median survival was 12 months (95% confidence interval [95% CI], 11.1-13.3 months) with a median follow-up of 11.8 months. Metastatic disease, age greater than or equal to 70, omission of androgen deprivation therapy (ADT), and lower income (P \u3c .05 for all) were all associated with reduced OS. Patients with prostate-specific antigen (PSA) greater than or equal to 33 ng/mL and those receiving ADT had better survival (P \u3c .05). Those with nonmetastatic disease were more likely to undergo prostatectomy and/or prostatic/pelvic radiation (P \u3c .0001). Prostatic/pelvic radiation in the nonmetastatic setting was associated with longer survival (P = .02). Though well powered, our study is limited by the selection bias inherent to all observational studies, despite the statistical methods utilized to reduce this effect. CONCLUSIONS: Although chemotherapy is the mainstay of treatment, radiation to the prostate/pelvis may be beneficial in the nonmetastatic setting. In addition to chemotherapy, ADT may benefit patients with an elevated PSA

Financial relationships between industry and principal investigators of US cooperative group randomized cancer clinical trials.

Financial conflicts of interest (FCOIs) could bias the potentially practice-changing oncologic randomized clinical trials (RCTs) of tomorrow. This investigation characterized the FCOIs of the principal investigators (PIs) of all currently accruing trials of the four (adult) cooperative groups of the National Clinical Trials Network. For our study, the PI list was first compiled, and each name was then searched in the CMS Open Payments database. For each transaction (general payments (GPs) or research funding (RF)), the amount/number/source of payments was recorded. Results showed that from 2014 to 2019, the 91 PIs collectively accepted nearly one-third of a billion dollars ($10 477 023 GPs and$320 096 233 RF). The mean and median GP was $6505 and$945, respectively, and $301 693 and$49 824 RF, respectively. Multivariable Gamma regression analysis revealed that higher GP sums were associated with RCTs involving any type of systemic therapy, and higher RF sums with medical oncologist PIs, trials with phase III components, and RCTs involving radiotherapy (P \u3c .05 for all). Both higher-volume GPs and RF were predicted by PIs having accepted payment(s) from the manufacturer of the drug utilized in their RCT (P \u3c .001 GP, P = .008 RF). Taken together, the main message of this investigation is that FCOIs may be particularly high in PIs of phase III systemic therapy trials, especially if the PI accepted payments from the manufacturer of the drug utilized in their trial. Such RCTs should be thoroughly scrutinized by medical journals, the FDA, and insurance companies for potential industry bias that could influence the integrity of their conclusions