Final outcomes analysis of the cell product SQZ-PBMC-HPV Phase 1 trial in incurable HPV16+ solid tumors shows improved overall survival in patients with increased CD8+ T cell tumor infiltration.

Cancer vaccines strive to induce robust, antigen-targeted, T-cell-mediated immune responses but have struggled to produce meaningful regression in solid tumors. An autologous cell vaccine, SQZ-PBMC-HPV, was developed by SQZ Biotechnologies using microfluidic squeezing technology to load PBMCs with HPV16 E6 and E7 antigens in HLA-A*02+ patients. The SQZ-PBMC-HPV-101 Phase 1 trial (NCT04084951) enrolled patients with incurable HPV16+ cancers. Here, we present a post hoc analysis of the relationship between Posttreatment CD8+ T cell infiltration and patient outcomes. SQZ-PBMC-HPV was administered as monotherapy every 3 weeks. Tumor samples were collected pre-dose and post-dose 4 weeks after treatment start. Biomarkers including CD8, MHC-I, E6, E7, GZMB, and Ki67 were evaluated by immunohistochemistry, immunofluorescence, and RNA in situ hybridization, and were correlated with clinical response, survival, and drug product composition. Eighteen patients had paired pre- and post-dose biopsies. Six (33%) had an increase in CD8+ T cell density in tumor parenchyma between screening and C2D8. Patients with increased CD8+ T cell density had improved disease control rate (66.7% vs 16.7%) and median overall survival (606.5 days vs 170.0 days, p = 0.0078). Drug product was significantly enriched for higher T cells and lower monocytes in the increased CD8+ T cell density group. In patients with incurable HPV16+ solid tumors treated with SQZ-PBMC-HPV, an increase in CD8+ T cell density within the tumor parenchyma was associated with superior disease control rate and overall survival. The product composition for patients with increased CD8+ T cell density was enriched for T cells.

Impact of Adjuvant Radiotherapy Setting on Quality-of-Life in Head and Neck Squamous Cell Carcinoma.

OBJECTIVE: To determine differences in post-treatment QoL across treatment settings in patients receiving adjuvant radiation therapy for head and neck squamous cell carcinoma (HNSCC). METHODS: This was a prospective observational cohort study of patients with HNSCC initially evaluated in a head and neck surgical oncologic and reconstructive clinic at an academic medical center (AMC). Participants were enrolled prior to treatment in a prospective registry collecting demographic, social, and clinical data. Physical and social-emotional QoL (phys-QoL and soc-QoL, respectively) was measured using the University of Washington-QoL questionnaire at pre-treatment and post-treatment visits. RESULTS: A cohort of 177 patients, primarily male and White with an average age of 61.2 ± 11.2 years, met inclusion criteria. Most patients presented with oral cavity tumors (n = 132, 74.6%), had non-HPV-mediated disease (n = 97, 61.8%), and were classified as Stage IVa (n = 72, 42.8%). After controlling for covariates, patients treated at community medical centers (CMCs) reported a 7.15-point lower phys-QoL compared with those treated at AMCs (95% CI: -13.96 to -0.35, p = 0.040) up to 12 months post-treatment. Additionally, patients who were treated at CMCs had a 5.77-point (-11.86-0.31, p = 0.063) lower soc-QoL score compared with those treated at an AMC, which was not statistically significant. CONCLUSION: This study revealed that HNSCC patients treated with radiation at AMCs reported significantly greater phys-QoL in their first-year post-treatment compared to those treated at CMCs, but soc-QoL did not differ significantly. Further observational studies are needed to explore potential factors, including treatment planning and cancer resource engagement, behind disparities between AMCs and CMCs. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:3645-3655, 2024.

Anaplastic large cell lymphoma of breast masquerading suppurative mastitis on cytology / Linfoma anaplásico de células grandes de mama enmascarando mastitis supurativa en citología

Breast is an uncommon site of extra nodal lymphoma accounting for 2.2% of all extra nodal lymphomas. B cell lymphomas are more common than T cell types. The most common subtype is Diffuse Large B Cell Lymphoma. Breast lymphoma is very challenging to diagnose as it has nonspecific clinical and radiological features. We report a rare case of primary T cell lymphoma in a 20-year-old female. It was misdiagnosed as abscess on ultrasound and as suppurative mastitis on fine needle aspiration cytology (FNAC). However, excisional biopsy was suggestive of lymphoma and immunohistochemistry confirmed it as ALK positive, anaplastic large cell lymphoma. Even though FNAC is a part of the diagnostic triad for breast lesions, potential pitfalls cannot be overlooked and must be correlated with biopsy. (AU)

La mama es un sitio poco frecuente de linfoma extraganglionar que representa el 2,2 % de todos los linfomas extraganglionares. Los linfomas de células B son más comunes que los tipos de células T. El subtipo más común es el linfoma difuso de células B grandes. El linfoma de mama es muy difícil de diagnosticar, ya que tiene características clínicas y radiológicas inespecíficas. Presentamos un caso raro de linfoma primario de células T en una mujer de 20 años. Fue mal diagnosticado como absceso en ultrasonido y como mastitis supurativa en citología por aspiración con aguja fina (FNAC). Sin embargo, la biopsia por escisión sugirió linfoma y la inmunohistoquímica lo confirmó como linfoma anaplásico de células grandes ALK positivo. Aunque la FNAC es parte de la tríada diagnóstica de las lesiones mamarias, no se pueden pasar por alto los peligros potenciales y se deben correlacionar con la biopsia. (AU)