'Le Roi est mort, vive le Roi': New Roles of Radiotherapy in the Treatment of Lymphomas in Combination With Immunotherapy.

BACKGROUND: immunotherapy (IT), including checkpoint inhibitors (CIs) and Chimeric Antigen Receptor T cell therapy (CAR-T) revolutionized the treatment of relapsing or refractory (r/r) lymphoma. Several preliminary experiences evaluated concomitant administration of radiotherapy and IT. METHODS: we performed a systematic review of current literature as of March 30, 2020. A total of 1090 records was retrieved, 42 articles were selected on the basis of title and abstract and, after the removal of analyses with no original data or insufficient clinical information, 28 papers were included in the review. RESULTS: previous studies were mostly represented by case reports/series or small cohorts. Nonetheless, combination of radiotherapy and CIs or CAR-T led to promising outcomes, resulting in extremely high rates of complete response and improving progression free and overall survival compared with data from recent clinical trials. Combination of RT and CIs had a fair toxicity profile with no reports of severe side effects. Within the limits of the small cohorts retrieved, RT seems a superior option compared with systemic treatment as a 'bridge' to CAR-T and could as well reduce severe complications rates. Radiotherapy could elicit immune response against lymphoma, as demonstrated by multiple cases of abscopal effect and its inclusion in anti-neoplastic vaccines protocols. CONCLUSION: The results of this review warrant the evaluation of combination of RT and immunotherapy in larger and preferably prospective and randomized cohorts to confirm these preliminary impressive outcomes. The optimal dose, fractionation and timing of RT still have to be clarified.

Long-Term Outcomes of Immunohistochemically Defined Subtypes of Breast Cancer Less Than or Equal to 2 cm After Breast-Conserving Surgery.

BACKGROUND: Molecular subtype predicts the prognosis of early-stage breast cancer patients. We assessed the long-term outcomes of breast cancer ≤2 cm treated with breast-conserving surgery (BCS) and stratified according to an immunohistochemically (IHC)-based subtype definition. METHODS: This retrospective study was conducted from a prospectively collected database. Included patients had pT1, any N, M0 breast cancer after BCS (without anti-HER2 therapy) and available information on estrogen receptor (ER), progesterone receptor (PR), HER2 status, Ki-67 index. Five IHC-defined subtypes were identified: luminal A-like (ER and/or PR-positive/HER2-negative/Ki-67 < 20%), luminal B-like/HER2-negative (ER and/or PR-positive/HER2-negative/Ki-67 ≥ 20%), luminal B-like/HER2-positive (ER and/or PR-positive/HER2-positive/any Ki-67 value), HER2-positive/nonluminal (ER and PR-negative/HER2-positive), and triple-negative (ER and PR-negative/HER2-negative). RESULTS: We analyzed 184 (65%) luminal A-like, 57 (20%) luminal B-like/HER2-negative, 17 (6%) luminal B-like/HER2-positive, 6 (2%) HER2-positive/nonluminal, and 18 (7%) triple-negative patients. Median follow-up was 112 (interquartile range 94-125) mo. The cumulative 5- and 10-y local recurrence (LR) rates were 1.5% and 4%, respectively. The cumulative 5- and 10-y distant recurrence (DR) rates were 3% and 8%, respectively. The Cox regression revealed that HER2-positive/nonluminal subtypes had the highest risk of LR (P = 0.0025). The luminal B-like/HER2-positive subtypes had the highest risk of DR (P = 0.0019). HER2 positivity carried a higher risk of DR in women with luminal breast cancer who completed 5 y of adjuvant hormonal therapy (P = 0.02). CONCLUSIONS: The IHC-defined subtype impacts on the prognosis of breast cancer ≤2 cm after BCS, determining significant differences in LR and DR rates. In the pre-"anti-HER2 therapy" era, patients with HER2-positive/nonluminal or luminal B-like/HER2-positive subtype had worse long-term outcomes than those with luminal A-like subtype.