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Simple Summary: Detecting circulating tumor DNA (ctDNA) in the blood has emerged as a valuable method for evaluating several different cancers. Most anal cancers are caused by HPV infection, which is typically identified through the examination of tissue specimens. In this study, we describe a novel method for detecting HPV in the ctDNA using next-generation DNA sequencing on blood samples from patients with advanced anal cancer. The assay was able to detect multiple types of HPV, including uncommon variants. Additionally, the assay appeared to correlate with the disease burden and response to treatment. HPV DNA can often integrate into cancer DNA, which was detectable using our assay, and we show that this may prognosticate which patients are more resistant to treatment. Background: To extend the practicality of liquid biopsy beyond the historical HPV circulating tumor DNA (ctDNA) assays, we evaluated the clinical relevance of a novel next-generation sequencing HPV ctDNA assay in patients with locally advanced and metastatic squamous cell cancer of the anal canal (mSCCA). Methods: ctDNA isolated from the plasma of patients with mSCCA was sequenced using a 1.4 Mb hybrid-capture target-enrichment panel covering the whole genome sequences of all 193 HPV types. The HPV type, copy number (CN), and integration sites were determined using a bioinformatic pipeline. Results: A total of 77 plasma samples from 28 patients with HPV-related SCCA were retrospectively analyzed. HPV ctDNA was detected in 26 cases (93%) (including uncommon subtypes). The median HPV CN was higher in metastatic versus locally recurrent/unresectable SCCA (p = 0.043). Changes in the HPV CN were concordant with the radiographic response (p = 0.027). An integration event was detected in 23 patients (82%), with presumed episomal HPV DNA present in the remaining patients. Higher HPV integration (a mean of ≥1 integration across samples) was associated with a worse overall survival from the start of immunotherapy (13.6 months versus 36.0 months; p = 0.003). Conclusions: Using HPV-informed next-generation sequencing of the ctDNA, we found changes in the HPV CN correlated with the treatment response and that HPV integration detected in the ctDNA is an unfavorable prognostic biomarker. [ABSTRACT FROM AUTHOR]

🧬ðŸ"¬ @VivekSubbiah & colleagues delve into the @ASCO #TAPURStudy, shedding light on the importance of targeting ALL #BRAFAlterations, beyond V600E. (Re)-search continues, urging us to push the boundaries and unlock new possibilities in #PrecisionMedicine. #CancerResearch #JCOPO [ABSTRACT FROM AUTHOR]

Understanding the landscape of KRAS mutations in #CRC is crucial with over 2.8M annual diagnoses worldwide. Explore promising therapies and ongoing challenges in this comprehensive review. #CancerResearch #KRAS #ColorectalCancer [ABSTRACT FROM AUTHOR]

VivekSubbiah & colleagues delve into the @ASCO #TAPURStudy, shedding light on the importance of targeting ALL #BRAFAlterations, beyond V600E. (Re)-search continues, urging us to push the boundaries and unlock new possibilities in #PrecisionMedicine. #CancerResearch #JCOPO [ABSTRACT FROM AUTHOR]

This article discusses two cases of metastatic pancreatic cancer that showed sustained disease control with targeted therapy using selpercatinib, a selective inhibitor of the RET tyrosine kinase receptor. Pancreatic cancer is a deadly disease with limited treatment options, but targeted therapies matched to specific molecular alterations have shown promise. The patients in these cases had RET fusion-positive pancreatic cancer and achieved significant reductions in tumor size and prolonged disease response with selpercatinib. The article highlights the importance of comprehensive genomic tumor profiling and suggests that RET inhibition should be considered as a first-line treatment option for eligible patients. However, the incidence of RET fusions in pancreatic cancer is low, and further research is needed to establish conclusive evidence. [Extracted from the article]

Poly (ADP-ribose) polymerase inhibitors (PARPi) have significantly changed the treatment landscape for tumours harbouring defects in genes involved in homologous repair (HR) such as BRCA1 and BRCA2. Despite initial responsiveness to PARPi, tumours eventually develop resistance through a variety of mechanisms. Rational combination strategies involving PARPi have been explored and are in various stages of clinical development. PARPi combinations have the potential to enhance efficacy through synergistic activity, and also potentially sensitise innately PARPi-resistant tumours to PARPi. Initial combinations involving PARPi with chemotherapy were hindered by significant overlapping haematologic toxicity, but newer combinations with fewer toxicities and more targeted approaches are undergoing evaluation. In this review, we discuss the mechanisms of PARPi resistance and review the rationale and clinical evidence for various PARPi combinations including combinations with chemotherapy, immunotherapy, and targeted therapies. We also highlight emerging PARPi combinations with promising preclinical evidence. [ABSTRACT FROM AUTHOR]

Factors correlated with biopsy tissue adequacy and the prevalence of within-biopsy variability were evaluated. Totally, 1149 research biopsies were performed on 686 patients from which 5090 cores were assessed. Biopsy cores were reviewed for malignant percentage (estimated percentage of cells in the core that were malignant) and malignant area (estimated area occupied by malignant cells). Linear mixed models and generalized linear mixed models were used for the analysis. A total of 641 (55.8%) biopsies contained a core with <10% malignant percentage (inadequate core). The chance of an inadequate core was not influenced by core order, though the malignant area decreased with each consecutive core (p < 0.001). Younger age, bone biopsy location, appendiceal tumor pathology, and responding/stable disease prior to biopsy increased the odds of a biopsy containing zero adequate cores. Within-biopsy variability in core adequacy is prevalent and suggests the need for histological tumor quality assessment of each core in order to optimize translational analyses. [ABSTRACT FROM AUTHOR]

Background: The standard of care for CNS lymphoma typically includes high dose methotrexate followed by whole brain radiation therapy, but there is an increased risk of neurotoxicity with this regimen. In our institution, we offered stereotactic radiosurgery (SRS) for disease refractory to HD-MTX in a subset of patients. A search of the literature on this modality for CNS lymphoma was also conducted. Methods: Medical records of six patients who received partial brain radiation therapy for persistent CNS lymphoma were reviewed. SRS was given via 1–3 fractions to doses of 21 or 24 Gy. PubMed, SCOPUS, and Cochrane Library databases were systematically searched for articles reporting on outcomes for CNS lymphoma treated with SRS. Results: Six patients (eleven lesions) were treated with SRS for CNS lymphomas. Median follow up was 15.6 months (range 3.3–37.8). Median RT dose per lesion was 21 Gy and median time to progression was 12.7 months. Median overall survival was not reached. Four patients had distant intracranial failure with two developing local recurrence. The search strategy yielded 16 studies of which only one was prospective and included a control group. 183 out of 256 evaluated lesions (69%) responded completely to treatment and 13 of 204 patients (6%) recurred within the treatment area at last follow-up. Overall, the treatment was well tolerated. Conclusion: SRS may provide favorable local control in patients with refractory CNS lymphomas. A prospective trial is warranted to validate the efficacy of such an approach. [ABSTRACT FROM AUTHOR]

Purpose/objectives: We report the outcomes of the largest cohort to date of patients receiving both bevacizumab (BEV) and fractionated stereotactic radiotherapy (FSRT) for progressive or recurrent high grade glioma (HGG). Furthermore, the sequence of these two treatment regimens was analyzed to determine an optimal treatment paradigm for recurrent HGG.Materials/methods: After Institutional Review Board approval, patients with pathologically confirmed WHO grade III anaplastic astrocytoma (AA) or IV glioblastoma multiforme (GBM) glioma who subsequently underwent re-irradiation at recurrence with FSRT were retrospectively reviewed. Patients from this group who had received BEV were also identified. Survival from initial diagnosis, as well as from recurrence and re-irradiation, were analyzed as study endpoints. Date of recurrence was defined as the date of radiographic evidence of progressive/recurrent disease. Kaplan-Meier curves were generated utilizing a log-rank test with a p-value ≤ 0.05 considered significant to compare treatment sequences in terms of survival outcomes.Results: A total of 118 patients with recurrent/progressive HGG (GBM = 87, AA = 31) had received both BEV and FSRT. Patient characteristics were as follows: median KPS at recurrence was 80 (range 50-100); median age at recurrence was 57 years; median time to radiographic recurrence/progression was 10.8 months (mo) and 33.1% of patients had surgery for recurrence. The median time from the start of BEV to FSRT was 6.4 months and from FSRT to the start of BEV was 5.1 months. For the entire cohort, median overall survival (OS) was 26.7 months and median survival time (MST) from recurrence was 13.8 months (24.4 months and 11.9 months for GBM only). In patients that received BEV prior to FSRT (n = 50), median OS and MST from recurrence were 25.2 and 13.3 months respectively. In patients receiving FSRT first (n = 56), median OS and MST from recurrence were 28.8 months and 13.9 months, respectively. Sequencing of BEV and FSRT at recurrence was not significantly associated with OS (p = 0.08) or median survival from recurrence (p = 0.75).Conclusions: The combination of FSRT and BEV for recurrent/progressive HGG provides promising results in terms of overall survival and survival from recurrence. Combining these treatment modalities appears to improve upon the historic outcomes of either treatment alone. The outcomes data from this study support the ongoing RTOG trial exploring the combination of BEV and FSRT for recurrent HGG. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma predominantly occurs in the 6th and 7th decades of life. The optimal treatment paradigm for elderly patients is not well established. We sampled current worldwide management strategies for elderly patients with newly diagnosed glioblastoma.Methods: A web-based survey was developed and distributed to 168 radiation oncologists, neuro-oncologists and neurosurgeons identified through the United Council for Neurologic Subspecialties and the CNS committees for North American, European and Asian Organizations. Questions addressed treatment recommendations in order to determine whether management consensus exists in this patient subset.Results: There were 68 (40%) respondents. Across respondents, the most important factors directing treatment were KPS (94%) and MGMT methylation status (71%). Only 37% of respondents strictly factor in age when making treatment recommendations with 59% defining elderly as greater than 70 years-old. The most common treatment recommendations for MGMT-methylated elderly patients with KPS > 70 were as follows: standard chemoRT (49%), short course chemoRT (39%), and temozolomide alone (30%). The most common treatment recommendations for MGMT-unmethylated patients with KPS > 70 were as follows: short course RT alone (51%), standard chemoRT (38%), and short course chemoRT (28%). Treatment recommendations for patients with KPS < 50 were short course RT alone (40%), best supportive care (57%), or TMZ alone (17%). Individuals practicing in North America were significantly more likely to recommend standard chemoradiation for patients compared to their European counterparts.Conclusion: Worldwide treatment recommendations for elderly patients with newly diagnosed GBM vary widely. Further randomized studies are needed to elucidate the optimal treatment strategy for this subset of patients. [ABSTRACT FROM AUTHOR]

Bevacizumab failure is a major clinical problem in the management of high grade gliomas (HGG), with a median overall survival (OS) of < 4 months. This study evaluated the feasibility and efficacy of fractionated stereotactic re-irradiation (FSRT) for patients progressed after Bevacizumab treatment. Retrospective review was conducted of 36 patients treated with FSRT after progression on bevacizumab. FSRT was most commonly delivered in 3.5 Gy fractions to a total dose of 35 Gy. Survival from initial diagnosis, as well as from recurrence and re-irradiation, were utilized as study endpoints. Univariate and multivariate analysis was performed. The median time from initial bevacizumab treatment to FSRT was 8.5 months. The median plan target volume for FSRT was 27.5 cc. The median OS from FSRT was 4.8 months. FSRT treatment was well tolerated with no grade 3 or higher toxicity. Favorable outcomes were observed in patients with recurrent HGG who received salvage FSRT after bevacizumab failure. The treatment was well tolerated. Prospective study is warranted to further evaluate the efficacy of salvage FSRT for selected patients with recurrent HGG amenable to FSRT, who had failed bevacizumab treatment. [ABSTRACT FROM AUTHOR]

The fourth author’s name was incorrect in the initial online publication. The original article has been corrected. [ABSTRACT FROM AUTHOR]