OBJECTIVE:Postoperative radiation therapy (PORT) initiation within 6 weeks of surgery is associated with improved oncologic outcomes in head and neck cancer, but delays remain common. Oncology nurse navigators (ONN) may improve care coordination. This study evaluates time to PORT following transoral robotic surgery (TORS) for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) after ONN implementation. STUDY DESIGN:Retrospective chart review. SETTING:Academic tertiary care center. METHODS:Patients with HPV-associated OPSCC treated with TORS followed by PORT between January 2016 and March 2024 were included. RESULTS:Ninety-nine patients were included. Median age was 60 years and 85.9% were male. 57.6% were treated after ONN implementation. Most received PORT within our integrated academic health system (75.8%). Following ONN implementation, time from TORS to PORT decreased from 50 to 44 days (P = .02), and was associated with treatment within the integrated academic health system (52-43 days, P = .01), adjuvant chemoradiation therapy (CRT) (56-44 days, P = .02), and adjuvant proton beam therapy (PBT) (52-44 days, P = .004). Among PBT-treated patients, PORT initiation within 6 weeks increased from 6.7% to 38.3% (P = .02). The proportion of patients completing their adjuvant treatment within 100 days of TORS increased from 61.9% to 93% (P < .001). CONCLUSION:ONN implementation is associated with earlier PORT initiation and shorter treatment package time following TORS for HPV-associated OPSCC, with the greatest improvement observed among patients receiving PBT, CRT, and those treated within the integrated academic health system.

OBJECTIVE:While smoking has been implicated as a risk factor for recurrence in HPV-associated oropharyngeal squamous cell cancer (OPSCC) treated with definitive chemoradiation, its prognostic impact on surgically treated OPSCC is less clear. DATA SOURCES:MEDLINE, Embase, CENTRAL, and Scopus. REVIEW METHODS:Articles describing patients with HPV-associated OPSCC treated with transoral robotic surgery (TORS), which reported oncologic outcomes by smoking history, were included. RESULTS:2079 patients were included across 12 studies. Median age was 58.5 years, and 1808 (87.0%) were male. HPV-associated disease was reported in 1681 (80.9%) patients. T stage was most commonly T2 in 831 (40.0%) and T1 in 764 (36.7%). N stage was N2 in 854 (41.1%), N1 in 544 (26.2%), and N0 in 307 (14.8%). 931 (44.8%) were considered individuals with a smoking history, while 1045 (50.3%) were considered without a smoking history. Median follow up was 33.7 months. Meta-analysis using a fixed effects model demonstrated an overall hazard ratio of 1.4 (95% confidence interval 1.0-2.0) for disease recurrence, 2.7 (95% confidence interval 1.5-4.8) for overall survival, and 1.4 (95% confidence interval 0.4-4.6) for disease specific survival. CONCLUSIONS:In this population of predominantly HPV-associated OPSCC treated with TORS, meta-analysis demonstrated no significant difference in recurrence-free survival or disease-specific survival between individuals with and without a smoking history. Individuals with a smoking history appeared to have worse overall survival, although only five studies reported on this outcome. Further research is required to clarify the prognostic influence of smoking on OPSCC treated with TORS.

OBJECTIVE:Smoking has been identified as a risk factor for recurrence in HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) treated with definitive chemoradiation. Whether the same prognostic significance holds with surgical treatment such as transoral robotic surgery (TORS) is less well studied. STUDY DESIGN:Retrospective review. SETTING:Tertiary care academic center. METHODS:Patients with HPV-associated OPSCC treated with TORS from January 2016 to December 2023 were included. Demographics, smoking history, disease characteristics, treatment, and oncologic outcomes were collected. RESULTS:156 patients were included. 87.2% were male with median age 60.0 years. Seventy-seven were never smokers, 63 former smokers, and 16 current smokers, with a median 20 pack-years among ever smokers. Three local, 6 regional, and ten distant metastases were identified, with 6 deaths, over a median 2.2 years of follow up. When comparing never, former, and current smokers, ever smokers demonstrated more advanced pathologic nodal staging (P = .03) and extranodal extension (P = .05). When comparing never and ever smokers, never smokers were younger (P = .04), and primary site differed with borderline significance (P = .05). Ever smokers again had more advanced nodal stage (P = .01) and extranodal extension (P = .02). There were no significant differences in adjuvant treatment, disease recurrence, or death by smoking history. There were no significant differences apart from age when analyzed using a 10 or 20-pack-year smoking history cutoff (P = .01, P = .02). CONCLUSION:Smoking history is associated with more advanced nodal stage and extranodal extension. However, smoking does not appear to influence recurrence or death in the setting of HPV-associated OPSCC definitively treated with TORS.

Abstract Background: Chimeric antigen receptor (CAR) T cells targeting B-cell maturation antigen (BCMA) have exhibited unprecedented efficacy with >70% initial response rate in patients with relapsed/refractory multiple myeloma (RRMM), which led to FDA approval of 2 CAR T products: ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel). However, long-term clinical outcomes vary markedly in RRMM patients. Prior studies have shown that specific states of CAR T cells, immature myeloma phenotype and hostile tumor microenvironment (TME) are associated with rapid relapse, but much remains to be elucidated regarding how CAR T cells evolve, persist and interact with host immunity over time in patients with distinct clinical outcomes. Methods: We acquired longitudinal bone marrow (BM) and peripheral blood mononuclear cells (PBMC) samples from 22 RRMM patients receiving 4 different anti-BCMA CAR T products, including cilta-cel (n=7), ide-cel (n=5), BB21217 (n=1) and orva-cel (n=9). The frequency and cell states of CAR and non-CAR T cells were assessed using flow cytometry and single-cell multi-omics (scRNA-seq). Results: At 1-month post-infusion, the frequency of CAR T cells in BM was significantly higher in durable responders (DR, PFS>12mo) than transient responders (TR, PFS<12mo) (p=0.04). Single-cell transcriptomic profiling further demonstrated CAR T cells in DR patients were significantly enriched in memory-like and proliferative states with less exhaustion phenotype. After 1 month, the frequency of persisting CAR T declined in all patients, but DR patients had significantly higher frequencies of CAR T cells than TR (p<0.0001). By 6 months, persisting CAR T cells in DR patients predominantly exhibited a non-canonical state (T persisters) possessing high expression levels of AP1 genes, NF-κB regulators, and effector cytokines as well as low level of exhaustion-related genes. By single-cell TCR tracking, these T persisters transitioned from multiple cell states at early timepoints. In DR patients, classical monocytes within the BM exhibited less immunosuppressive phenotype post CAR T infusion. Conclusions: Favorable clinical outcomes in RRMM patients are associated with greater expansion and persistence of CAR T. Durable responses are also associated with non-canonical CAR T cell states as well as a less immunosuppressive tumor microenvironment. These results provide insights into the determinants of durable clinical responses with anti-BCMA CAR T cells for RRMM. Citation Format: Kai Wu, Karen Law, Serena Kwek, Marcel Arias-Badia, Aram Lyu, Rachel Wolters, Averey Lea, Matthew Clark, Chang Liu, Ye Li, Ryan Owens, Lam Trieu, Alex Tran, Mark Bridge, Zenghua Fan, Alexander Cheung, Jeffrey Wolf, Andrew Portuguese, Jordan Gauthier, Thomas Martin, Justin Eyquem, Lawrence Fong. Non-canonical CAR T cell states correlate with durable therapeutic responses in multiple myeloma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3980.

Background The gut microbiota plays a critical role in regulating immune homeostasis and modulating responses to cancer immunotherapies. However, the impact of antibiotic-induced dysbiosis in patients with multiple myeloma (MM) treated with bispecific antibodies (BsAbs) remains unexplored. This multicenter, international study investigated whether antibiotic exposure prior to BsAb initiation alters the gut microbiome and affects clinical outcomes in patients with relapsed or refractory MM.Methods We retrospectively analyzed 237 adult patients with MM treated with CD3-engaging BsAbs across six academic institutions. Antibiotic exposure was defined as the administration of any broad-spectrum, non-prophylactic antibiotic within 30 days before BsAb initiation. Clinical outcomes included overall survival (OS), progression-free survival (PFS), and cumulative incidence of relapse, evaluated using Kaplan-Meier estimates, log-rank tests, and multivariable Cox and competing-risk regression models. Additionally, in a subset of 24 patients, peripheral blood samples were collected prior to BsAb infusion for immunophenotyping, cytokine profiling, and serum short-chain fatty acid (SCFA) quantification, while stool samples for 16S ribosomal RNA (rRNA) sequencing were collected in a subset of 19 patients.Results Broad-spectrum antibiotic exposure prior to BsAb therapy was associated with significantly inferior 1-year OS (60% (95% CI 44% to 81%) vs 77% (95% CI 71% to 83%), p=0.004) and PFS (26% (95% CI 14% to 47%) vs 53% (95% CI 46% to 61%), p<0.001), and higher relapse incidence (68% (95% CI 48% to 82%) vs 43% (95% CI 36% to 50%), p=0.004). In multivariable analyses, antibiotic exposure remained independently associated with poorer OS, PFS, and higher relapse risk. These associations were also observed within the subgroup of patients treated with CD3/B-cell maturation antibody-targeted BsAbs (n=155). Immunoprofiling revealed lower CD4+ T-cell counts (p=0.017) and reduced circulating cytokine levels among antibiotic-exposed patients. 16S rRNA sequencing demonstrated a marked depletion of SCFA-producing genera, including Roseburia and Eubacterium, accompanied by lower serum SCFA concentrations. Moreover, microbiota composition before BsAb treatment correlated with therapy response and treatment-related toxicity.Conclusions Antibiotic-induced dysbiosis prior to BsAb therapy is associated with impaired immune reconstitution and inferior clinical outcomes in MM. These findings underscore the importance of antibiotic stewardship and suggest that microbiota-preserving strategies could enhance the efficacy of BsAb therapy in MM.

ABSTRACT:Despite the success of B-cell maturation antigen (BCMA)-targeting chimeric antigen receptor (CAR) T cells (CAR-Ts) in multiple myeloma, patients with high-risk cytogenetic features continue to relapse most quickly and are in urgent need of additional therapeutic options. Here, we identify CD70, widely recognized as a favorable immunotherapy target in other cancers, as a specifically upregulated cell surface antigen in high-risk myeloma tumors. We use a structure-guided design to define a CD27-based anti-CD70 CAR-T design that outperforms all tested single-chain variable fragment-based CARs, leading to >80-fold improved CAR-T expansion in vivo. Epigenetic analysis via machine learning predicts key transcription factors and transcriptional networks driving CD70 upregulation in high-risk myeloma. Dual-targeting CAR-Ts against either CD70 or BCMA demonstrate a potential strategy to avoid antigen escape-mediated resistance. Together, these findings support the promise of targeting CD70 with optimized CAR-Ts in myeloma as well as future clinical translation of this approach.

B-cell maturation antigen (BCMA) directed chimeric antigen receptor T-cell therapy (CAR-T) has transformed the treatment of relapsed/refractory multiple myeloma (RRMM), yet relapse is still common for most patients. A variety of different salvage treatment strategies have been studied in the last several years to address several resistance mechanisms that lead to relapse after BCMA CAR-T. To date, there are no clear guidelines regarding treatment sequencing strategies for salvage therapy. This review will investigate the current landscape of available salvage therapies and data supporting their use, as well as possible treatment sequencing strategies to maximize clinical outcomes in this difficult-to-treat population.

Abstract Background: Chimeric antigen receptor (CAR) T cells targeting B-cell maturation antigen (BCMA) can induce >70% response rates in patients with relapsed/refractory multiple myeloma (RRMM). However, most patients ultimately relapse. There are two FDA-approved CAR T products: ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel), the former having much more durable responses. The mechanisms that mediate more durable responses with these CAR T cells is unknown. Previous studies have shown that specific cell states in the apheresis and infusion products are associated with long-term efficacy of anti-BCMA CAR therapy in MM and the relationship between durability of response and CAR T cell persistence remains unclear. Methods: We analyzed serial bone marrow and PBMC samples from 20 MM patients who received BCMA CAR T therapy, including cilta-cel, ide-cel, and JCARH125. Flow cytometry and single-cell RNAseq were used to evaluate the features of CAR T cells that are associated with durable clinical responses. Results: While CAR T cells were detectable but variable among patients at 1-month post infusion, the frequency of CAR T cells in bone marrow at 1-month post-infusion is positively correlated with progression free survival (PFS) in all MM patients (p=0.009). This association was also evident in patients just treated with cilta-cel (p= 0.008). By 6 months, CAR T cells could still be detected by high-throughput flowcytometry in the cilta-cel-treated patients, but CAR T cells were not detectable in most of the patients receiving the other 2 products. Cilta-cel CAR T cells predominantly possessed an effector-like surface phenotype at 1-moth post infusion in both CD8+ and CD4+ compartments in bone marrow. These CAR T cells shifted to effector memory and central memory T cell states by 6 months, respectively. For ide-cel and JCARH125, patients with more durable responses (>6mos) there was a significantly higher proportion of CAR T cells with CD8+ effector memory-like state at 1-month post infusion. Conclusions: Our data demonstrate that distinct anti-BCMA CAR T cell treatments lead to very different cellular outcomes: Cilta-cel CAR T cell treatment leads to greater expansion and persistence compared to other anti-BCMA CAR T cells. Cilta-cel CAR T cells also shift from the initial effector state to a memory phenotype. These results provide insights into features of more efficacious anti-BCMA CAR T cells that can help guide the future development of more durable treatments for MM. Citation Format: Kai Wu, Karen Law, Guy Ledergor, Chang Liu, Zenghua Fan, Vibha Gurunathan, Averey Lea, Matthew Clark, Serena Kwek, Alexander Cheung, Jeffrey Wolf, Ajai Chari, Anupuma Kumar, Justin Eyquem, Thomas Martin, Lawrence Fong. Expansion and persistence of anti-BCMA CAR T cells correlates with durability of responses in multiple myeloma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3617.

INTRODUCTION:Re-irradiation (re-RT) for recurrent head and neck cancer (rHNC) is challenging. We describe clinical outcomes and toxicity of proton therapy (PT) for recurrent HNC, and report genomic alterations associated with patterns of failure. MATERIALS & METHODS:We performed a retrospective analysis of rHNC patients treated with PT. Outcomes were estimated using the Kaplan-Meier method. Univariate (UVA) and multivariate analyses (MVA) were performed to assess multiple patient factors. Next-generation sequencing and genomic analyses were performed on available samples. RESULTS:Eighty-nine patients treated with PBS-PT for rHNC with a median follow-up of 12 mo (0-71 mo) were included. The 1- and 2-y local control (LC) rates were 80.8 % (95 % CI: 70.8-90.8) and 66.2 % (95 % CI: 50.7-81.7), and 1- and 2-y distant metastasis-free survival (DMFS) were 41.0 % (95 % CI: 30.0-52.0) and 26.3 % (95 % CI: 15.7-36.9). The median overall survival (OS) was 13 mo (95 % CI: 9.3-16.7). On UVA and MVA, smaller gross tumor volume (GTV) was associated with improved OS (HR 1.002, P = 0.004), DMFS (HR 1.002, P = 0.004), and PFS (HR 1.002, P = 0.014). There were 35 late Gr3 + toxicity events (30.3 %). Patients with higher candidate gene-specific mutation burden (genes with [OR] > 2, P < 0.05) had inferior PFS. TP53, NOTCH4, and ARID1B mutations were associated with inferior DMFS (OR > 2, P < 0.05). CONCLUSIONS:PBS-PT is effective at achieving LC for rHNC with favorable toxicity. Distant metastases are common, and associated with TP53, NOTCH4, and ARID1B mutations. Inclusion of genomic alterations in the clinical decision process may be warranted.

Minimal Residual Disease (MRD) assessment is a known surrogate marker for survival in multiple myeloma (MM). Here, we present a single institution’s experience assessing MRD by NGS of Ig genes and the long-term impact of depth of response as well as clonal diversity on the clinical outcome of a large population of MM patients; 482 MM patients at the University of California, San Francisco (UCSF) diagnosed from 2008 to 2020 were analyzed retrospectively. MRD assessment was performed by NGS. PFS curves were plotted by the Kaplan-Meier method. In the newly diagnosed group, 119 of 304, achieved MRD negativity at the level of 10− 6 at least once. These patients had a prolonged PFS versus patients who were persistently MRD positive at different levels (p > 0.0001). In the relapsed disease group, 64 of 178 achieved MRD negativity at 10− 6 and PFS was prolonged versus patients who remained MRD positive (p = 0.03). Three categories of MRD dynamics were defined by artificial intelligence: (A) patients with ≥ 3 consistently MRD negative samples, (B) patients with continuously declining but detectable clones, (C) patients with either increasing or a stable number of clones. Groups A and B had a more prolonged PFS than group C (p < 10− 7). Patients who were MRD positive and had not yet relapsed had a higher clonal diversity than those patients who were MRD positive and had relapsed. MRD dynamics can accurately predict disease evolution and drive clinical decision-making. Clonal Diversity could complement MRD assessment in the prediction of outcomes in MM.

OBJECTIVES:We sought to describe outcomes for locally advanced cutaneous squamous cell carcinoma (SCC) involving the parotid treated with volumetric modulated arc therapy (VMAT) versus pencil beam scanning proton beam therapy (PBT). MATERIALS AND METHODS:Patients were gathered from 2016 to 2022 from 5 sites of a large academic RT department; included patients were treated with RT and had parotid involvement by: direct extension of a cutaneous primary, parotid regional spread from a previously or contemporaneously resected but geographically separate cutaneous primary, or else primary parotid SCC (with a cutaneous primary ostensibly occult). Acute toxicities were provider-reported (CTCAE v5.0) and graded at each on treatment visit. Statistical analyses were conducted. RESULTS:Median follow-up was 12.9 months (1.3 - 72.8); 67 patients were included. Positive margins/extranodal extension were present in 34 cases; gross disease in 17. RT types: 39 (58.2 %) VMAT and 28 (41.8 %) PBT. Concurrent systemic therapy was delivered in 10 (14.9 %) patients. There were 17 treatment failures (25.4 %), median time of 168 days. Pathologically positive neck nodes were associated with locoregional recurrence (p = 0.015). Oral cavity, pharyngeal constrictor, and contralateral parotid doses were all significantly lower for PBT. Median weight change was -3.8 kg (-14.1 - 5.1) for VMAT and -3 kg (-16.8 - 3) for PBT (p = 0.013). Lower rates of ≥ grade 1 xerostomia (p = 0.002) and ≥ grade 1 dysguesia (p < 0.001) were demonstrated with PBT. CONCLUSIONS:Cutaneous SCC involving the parotid can be an aggressive clinical entity despite modern multimodal therapy. PBT offers significantly lower dose to organs at risk compared to VMAT, which seemingly yields diminished acute toxicities.

Purpose/Objective(s)Most patients with p16-positive oropharynx cancer (p16+OPC) receive contralateral elective nodal radiation therapy that improves regional control but increases acute and long-term toxicity. We hypothesize a validated volume reduction in the contralateral neck is effective with an improved toxicity profile in patients with p16+OPC receiving definitive or adjuvant radiation therapy.Materials/MethodsPatients with newly diagnosed p16+OPC without contralateral nodal involvement treated with primary proton or photon-based (chemo)radiation or adjuvant (chemo)radiation following Transoral Robotic Surgery (TORS) were eligible for enrollment. The reduced contralateral nodal volume included regions of level II and III based on high risk locations for contralateral nodal disease. The primary endpoint was elective out-of-field contralateral nodal failure. Dosimetric comparisons between standard versus reduced elective nodal volumes were analyzed. Acute toxicity was collected using CTCAE v4.0.ResultsFifty-two patients were enrolled of which 36 (69.2%) received definitive (chemo)radiation. Sixteen (30.8%) patients underwent adjuvant radiation following TORS of which 5 (31.2%) received concurrent platinum-based chemotherapy for high risk features. Proton therapy was used in 38 (73.1%) patients. There were no contralateral nodal failures at a median follow up of 15 months (range 1-24 months). For the first 20 patients enrolled, dosimetric comparison of the reduced contralateral elective nodal volumes to consensus elective nodal volumes demonstrated a decrease in the mean dose (18.5 Gy to 14.1 Gy [p<0.05]) and V30 Gy (21.3% to 11.6% [p<0.01]) of the contralateral parotid dose. Significant differences were independent of radiation modality or technology. Acute grade 3 toxicity was observed in 13 (25%) patients including 6 (11.5%) who received a PEG tube during treatment. There were no grade 4-5 acute toxicities, and at 6 months follow up no patients had retained a PEG tube.ConclusionSelective avoidance of nodal volumes at minimal risk in the N0 contralateral neck of patients with p16-positive oropharynx cancer can be safely performed while maintaining excellent regional control. Both dose to contralateral organs at risk and toxicities were favorable. Maturation of follow-up is ongoing to further support this de-intensification strategy.

ABSTRACT:Multiple myeloma is characterized by frequent clinical relapses after conventional therapy. Recently, chimeric antigen receptor (CAR) T cells targeting B-cell maturation antigen (BCMA) has been established as a treatment option for patients with relapsed or refractory disease. However, although >70% of patients initially respond to this treatment, clinical relapse and disease progression occur in most cases. Recent studies showed persistent expression of BCMA at the time of relapse, indicating that immune-intrinsic mechanisms may contribute to this resistance. Although there were no preexisting T-cell features associated with clinical outcomes, we found that patients with a durable response to CAR T-cell treatment had greater persistence of their CAR T cells than patients with transient clinical responses. They also possessed a significantly higher proportion of CD8+ T-effector memory cells. In contrast, patients with short-lived responses to treatment have increased frequencies of cytotoxic CD4+ CAR T cells. These cells expand in vivo early after infusion but express exhaustion markers (hepatitis A virus cellular receptor 2 [HAVCR2] and T-cell immunoglobulin and mucin domain-containing-3 [TIGIT]) and remain polyclonal. Finally, we demonstrate that nonclassical monocytes are enriched in the myeloma niche and may induce CAR T-cell dysfunction through mechanisms that include transforming growth factor β. These findings shed new light on the role of cytotoxic CD4+ T cells in disease progression after CAR T-cell therapy.

Multiple myeloma is a treatable, but currently incurable, hematological malignancy of plasma cells characterized by diverse and complex tumor genetics for which precision medicine approaches to treatment are lacking. The Multiple Myeloma Research Foundation’s Relating Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profile study ( NCT01454297 ) is a longitudinal, observational clinical study of newly diagnosed patients with multiple myeloma (n = 1,143) where tumor samples are characterized using whole-genome sequencing, whole-exome sequencing and RNA sequencing at diagnosis and progression, and clinical data are collected every 3 months. Analyses of the baseline cohort identified genes that are the target of recurrent gain-of-function and loss-of-function events. Consensus clustering identified 8 and 12 unique copy number and expression subtypes of myeloma, respectively, identifying high-risk genetic subtypes and elucidating many of the molecular underpinnings of these unique biological groups. Analysis of serial samples showed that 25.5% of patients transition to a high-risk expression subtype at progression. We observed robust expression of immunotherapy targets in this subtype, suggesting a potential therapeutic option. Longitudinal genomic and transcriptomic profiling of 1,143 patients with multiple myeloma by the Relating Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profile study yields an improved copy number and gene expression subtype scheme, most notably a high-risk proliferative subtype associated with complete loss of RB1 or MAX.

Cricket Frogs (Acris blanchardi) live about 1 y and undergo development quickly. In addition to relatively quick metamorphosis, as seen in past outdoor studies, active spermatogenesis in juvenile males can be observed as early as 60 d after metamorphosis, and female development (i.e., ovary and oviduct) is notably progressed prior to overwintering. We assessed life-history traits of field caught A. blanchardi over three time points and three Oklahoma locations. We also compared the development of wild A. blanchardi from one location to findings from previous studies using the same site. We captured cohorts of wild A. blanchardi in the fall (i.e., prior to overwintering), spring (i.e., first observation of emergence), and summer (i.e., first observation of active breeding). Besides general growth and development, we assessed gonadal maturation via histopathology. Ovary, oviduct, and testis development significantly varied among seasons; however, variation in testis development among seasons was less pronounced than ovary and oviduct development. Significant among-pond variation was limited to oviduct development. An assessment of field captured A. blanchardi from two previous years indicated significant year-toyear variation in ovary development but not oviduct or testis development. Despite observed differences in gonad development, variations were often predictable and could be potentially attributed to environmental factors (e.g., water temperature). Nonetheless, the results of our study provide specifics of A. blanchardi development that may be useful for future studies that wish to use this native species as an amphibian research model.

PBS-PT for recurrent HNC results in effective disease control and favorable toxicity. Patients with smaller GTV volume appear to have improved OS, PFS and DMFS, and may be better candidates. Those with shorter time to re-RT also have worse LRC. However, distant failure (DF) comprises a major failure pattern, and biomarkers to identify patients at risk for DF may improve clinical decision making.