Citations

Abstract The number of patients with primary cutaneous lymphoma (PCL) relative to other non-Hodgkin lymphomas (NHLs) is small and the number of subtypes large. Although clinical trial guidelines have been published for mycosis fungoides/Sézary syndrome, the most common type of PCL, none exist for the other PCLs. In addition, staging of the PCLs has been evolving based on new data on potential prognostic factors, diagnosis, and assessment methods of both skin and extracutaneous disease and a desire to align the latter with the Lugano guidelines for all NHLs. The International Society for Cutaneous Lymphomas (ISCL), the United States Cutaneous LymphomaConsortium (USCLC), and the Cutaneous Lymphoma Task Force of the European Organization for the Research and Treatment of Cancer (EORTC) now propose updated staging and guidelines for the study design, assessment, endpoints, and response criteria in clinical trials for all the PCLs in alignment with that of the Lugano guidelines. These recommendations provide standardized methodology that should facilitate planning and regulatory approval of new treatments for these lymphomas worldwide, encourage cooperative investigator-initiated trials, and help to assess the comparative efficacy of therapeutic agents tested across sites and studies.

Abstract Neuromyelitis optica is an autoimmune inflammatory disorder targeting aquaporin-4 water channels in CNS astrocytes. Histopathological descriptions of astrocytic lesions reported in neuromyelitis optica so far have emphasized a characteristic loss of aquaporin-4, with deposition of IgG and complement and lysis of astrocytes, but sublytic reactions have been underappreciated. We performed a multi-modality study of 23 neuromyelitis optica autopsy cases (clinically and/or pathologically confirmed; 337 tissue blocks). By evaluating astrocytic morphology, immunohistochemistry and AQP4 RNA transcripts, and their associations with demyelinating activity, we documented a spectrum of astrocytopathy in addition to complement deposition, microglial reaction, granulocyte infiltration and regenerating activity. Within advanced demyelinating lesions, and in periplaque areas, there was remarkable hypertrophic astrogliosis, more subtle than astrocytic lysis. A degenerative component was suggested by ‘dystrophic’ morphology, cytoplasmic vacuolation, Rosenthal fibres and associated stress protein markers. The abundance of AQP4 mRNA transcripts in sublytic reactive astrocytes devoid of aquaporin-4 protein supported in vivo restoration following IgG-induced aquaporin-4 endocytosis/degradation. Astrocytic alterations extending beyond demyelinating lesions speak to astrocytopathy being an early and primary event in the evolving neuromyelitis optica lesion. Focal astrocytopathy observed without aquaporin-4 loss or lytic complement component deposition verifies that astrocytic reactions in neuromyelitis optica are not solely dependent on IgG-mediated aquaporin-4 loss or lysis by complement or by IgG-dependent leucocyte mediators. We conclude that neuromyelitis optica reflects a global astrocytopathy, initiated by binding of IgG to aquaporin-4 and not simply definable by demyelination and astrocytic lysis. The spectrum of astrocytic morphological changes in neuromyelitis optica attests to the complexity of factors influencing the range of astrocytic physiological responses to a targeted attack by aquaporin-4-specific IgG. Sublytic astrocytic reactions are no doubt an important determinant of the lesion’s evolution and potential for repair. Pharmacological manipulation of the astrocytic stress response may offer new avenues for therapeutic intervention.

Abstract Purpose: Outcomes for resistant metastatic castration-resistant prostate cancer (CRPC) are poor. Stereotactic ablative radiotherapy (SABR) induces antitumor immunity in clinical and preclinical studies, but immunologic biomarkers are lacking. Patients and Methods: Eighty-nine patients with oligometastatic CRPC were identified by 11C-Choline-PET (Choline-PET) from August 2016 to December 2019 and treated with SABR. Prespecified coprimary endpoints were 2-year overall survival (OS) and PSA progression. Secondary endpoints included 2-year SABR-treated local failure and 6-month adverse events. Correlative studies included peripheral blood T-cell subpopulations before and after SABR. Results: 128 lesions in 89 patients were included in this analysis. Median OS was 29.3 months, and 1- and 2-year OS were 96% and 80%, respectively. PSA PFS was 40% at 1 year and 21% at 2 years. Local PFS was 84.4% and 75.3% at 1 and 2 years, respectively, and no grade ≥3 AEs were observed. Baseline high levels of tumor-reactive T cells (TTR; CD8+CD11ahigh) predicted superior local, PSA, and distant PFS. Baseline high levels of effector memory T cells (TEM; CCR7−CD45RA−) were associated with improved PSA PFS. An increase in TTR at day 14 from baseline was associated with superior OS. Conclusions: This is the first comprehensive effector T-cell immunophenotype analysis in a phase II trial before and after SABR in CRPC. Results are favorable and support the incorporation of immune-based markers in the design of future randomized trials in patients with oligometastatic CRPC treated with SABR.

256 Background: Ovarian cancer is the leading cause of gynecologic cancer mortality in the US. Given the high burden of disease and complexities in the provision of quality care, a multidisciplinary team approach is critical to optimal care delivery. In 2019, the Association of Community Cancer Centers (ACCC) launched a multiphase, stakeholder-driven initiative to improve care for this patient population. Results of a national survey of cancer programs to identify the needs of patients are reported here. Methods: A 20 question survey was developed by an expert steering committee including gynecologic oncologists, pathologists, genetic counselors, a nurse navigator, and cancer center administrators. The instrument was designed to collect data about cancer programs, key ovarian cancer patient needs, and barriers to and opportunities for improving ovarian cancer care. The online survey was open for participation for 4 weeks using the Qualtrics platform and distributed via email to ACCC and Society of Gynecologic Oncology members. Results: We received 26 total responses from Comprehensive Community (26%), NCI-Designed Comprehensive (22%), Academic Comprehensive (22%), and Integrated Network (13%) Cancer Programs. Annual ovarian cancer cases ranged from 22 to 190 (median: 50.5). 85% of programs has a multidisciplinary team for ovarian cancer and 61% were part of a referral network. On average, programs has 1.5 phase II and 2 phase III clinical trials currently available for ovarian cancer (all programs had at least 1 trial available). Palliative care and comprehensive symptom management was integrated into the first appointment (15%), integrated at the time of recurrence (4%), and most frequently, available by consult (81%). We assessed genetic testing practices at each program. Aggregated across programs, 79% of patients received germline multipanel testing, 71% germline BRCA only, 50% somatic multigene, and 51% somatic BRCA only. The frequency of consultations included: genetic counseling (75%), nurse navigation (75%), social work (50%), dietetics (40%), financial counseling (25%). Genetic evaluations were typically ordered by Gynecologic Oncology (88%), genetic counseling (4%), or both (8%). When asked what topic they would choose for a quality improvement project, genetic testing and counseling was the most frequent choice (46%), followed by clinical trials enrollment and availability (23%), multidisciplinary team care (19%), education on best practices (15%), palliative care (15%), and ancillary services (15%). Conclusions: Multidisciplinary care for ovarian cancer was common across a range of cancer programs but integration of palliative care, social work, dietetics, and financial counseling could be improved. Expanding clinical trials and genetic testing and counseling were the most frequently identified opportunities to improve ovarian cancer care.

Abstract We studied the performance of an algorithm combining multiplex polymerase chain reaction with phenotypic detection of extended-spectrum β-lactamases and carbapenemases directly from positive blood culture bottles in patients with gram-negative bacteremia and found good concordance with routine cultures. Such an algorithm may be a tool to improve time to optimal therapy in patients with gram-negative bacteremia.