Phase II Study of Palbociclib (PD-0332991) in CCND1, 2, or 3 Amplification: Results from the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol Z1B.

PURPOSE: Cyclin D/CDK4/6 is critical in controlling the G1 to S checkpoint. CCND, the gene encoding cyclin D, is known to be amplified in a variety of solid tumors. Palbociclib is an oral CDK4/6 inhibitor, approved in advanced breast cancer in combination with endocrine therapy. We explored the efficacy of palbociclib in patients with nonbreast solid tumors containing an amplification in CCND1, 2, or 3. PATIENTS AND METHODS: Patients with tumors containing a CCND1, 2, or 3 amplification and expression of the retinoblastoma protein were assigned to subprotocol Z1B and received palbociclib 125 mg once daily for 21 days of a 28-day cycle. Tumor response was assessed every two cycles. RESULTS: Forty patients were assigned to subprotocol Z1B; 4 patients had outside assays identifying the CCND1, 2, or 3 amplification and were not confirmed centrally; 3 were ineligible and 2 were not treated (1 untreated patient was also ineligible), leaving 32 evaluable patients for this analysis. There were no partial responses; 12 patients (37.5%) had stable disease as best response. There were seven deaths on study, all during cycle 1 and attributable to disease progression. Median progression-free survival was 1.8 months. The most common toxicities were leukopenia (n = 21, 55%) and neutropenia (n = 19, 50%); neutropenia was the most common grade 3/4 event (n = 12, 32%). CONCLUSIONS: Palbociclib was not effective at treating nonbreast solid tumors with a CCND1, 2, or 3 amplification in this cohort. These data do not support further investigation of single-agent palbociclib in tumors with CCND1, 2, or 3 amplification.

Palliative care use and utilization determinants among patients treated for advanced stage lung cancer care in the community and academic medical setting.

PURPOSE: Despite clinical guidelines, palliative care is underutilized during advanced stage lung cancer treatment. To inform interventions to increase its use, patient-level barriers and facilitators (i.e., determinants) need to be characterized, especially among patients living in rural areas or those receiving treatment outside academic medical centers. METHODS: Between 2020 and 2021, advanced stage lung cancer patients (n = 77; 62% rural; 58% receiving care in the community) completed a one-time survey assessing palliative care use and its determinants. Univariate and bivariate analyses described palliative care use and determinants and compared scores by patient demographic (e.g., rural vs. urban) and treatment setting (e.g., community vs. academic medical center) factors. RESULTS: Roughly half said they had never met with a palliative care doctor (49.4%) or nurse (58.4%) as part of cancer care. Only 18% said they knew what palliative care was and could explain it; 17% thought it was the same as hospice. After palliative care was distinguished from hospice, the most frequently cited reasons patients stated they would not seek palliative care were uncertainty about what it would offer (65%), concerns about insurance coverage (63%), difficulty attending multiple appointments (60%), and lack of discussion with an oncologist (59%). The most common reasons patients stated they would seek palliative care were a desire to control pain (62%), oncologist recommendation (58%), and coping support for family and friends (55%). CONCLUSION: Interventions should address knowledge and misconceptions, assess care needs, and facilitate communication between patients and oncologists about palliative care.

Craniosynostosis: Clinical Presentation, Genetics, and Prenatal Diagnosis.

IMPORTANCE: Craniosynostosis is a fetal condition caused by premature closure of the cranial sutures. Through provider awareness, we can raise suspicion in high-risk individuals, increase prenatal detection, optimize genetic testing, perform appropriate antenatal surveillance and delivery planning, and allow for a comprehensive, multidisciplinary approach to treatment. OBJECTIVE: The aim of this study was to review what is currently known regarding the genetics, pathophysiology, diagnosis, and treatment of craniosynostosis for the obstetric care provider. EVIDENCE ACQUISITION: A comprehensive literature review was performed using the PubMed database with the search term "craniosynostosis." The search was limited to the English language. RESULTS: A total of 220 articles were identified, and a total of 53 were used in completion of this article. The results highlight the multiple factors involved with abnormal suture formation, including various genetic factors. Although rare at this time, prenatal detection can allow families to prepare and practitioners to provide appropriate clinical treatment. Both 3-dimensional sonography and magnetic resonance imaging have been identified as modalities to aid in detection for high-risk individuals. Early referral allows for less-invasive surgical outcomes with lower complication rates. RESULTS: Familiarity with craniosynostosis among obstetric providers can improve patient counseling, prenatal detection rates, and appropriate antepartum, intrapartum, and postpartum counseling.

The role of salvage reirradiation for malignant gliomas that progress on bevacizumab.

Bevacizumab and irinotecan are effective against recurrent malignant gliomas. However, at subsequent progression, patients rarely respond to a second bevacizumab-containing chemotherapeutic regimen. Salvage re-irradiation with bevacizumab for recurrent but bevacizumab naive malignant gliomas showed encouraging results. We performed a retrospective review of the medical records of 23 patients treated with either fractionated stereotactic radiotherapy (FSRT) or stereotactic radiosurgery (SRS) after progression on an initial bevacizumab regimen. Patients were treated after re-irradiation with bevacizumab but combined with a different chemotherapy. We then compared them to another 23 patients who progressed on an initial bevacizumab + chemotherapy regimen. These patients did not receive re-irradiation but bevacizumab was continued combined with a different chemotherapy. Patients treated with FSRT/SRS/bevacizumab had a longer median progression-free period (2.6 vs. 1. 7 months, P = 0.009), longer median post FSRT/SRS treatment survival (7.2 vs. 3.3 months, P = 0.03) and higher radiographic response rate (22 vs. 0%, P = 0.049). FSRT or SRS followed by bevacizumab + chemotherapy may have a role for patients who progress on bevacizumab.