Theranostic near-infrared-IIb emitting nanoprobes for promoting immunogenic radiotherapy and abscopal effects against cancer metastasis

Radiotherapy is an important therapeutic strategy for cancer treatment through direct damage to cancer cells and augmentation of antitumor immune responses. However, the efficacy of radiotherapy is limited by hypoxia-mediated radioresistance and immunosuppression in tumor microenvironment. Here, we construct a stabilized theranostic nanoprobe based on quantum dots emitting in the near-infrared IIb (NIR-IIb, 1,500–1,700 nm) window modified by catalase, arginine–glycine–aspartate peptides and poly(ethylene glycol). We demonstrate that the nanoprobes effectively aggregate in the tumor site to locate the tumor region, thereby realizing precision radiotherapy with few side-effects. In addition, nanoprobes relieve intratumoral hypoxia and reduce the tumor infiltration of immunosuppressive cells. Moreover, the nanoprobes promote the immunogenic cell death of cancer cells to trigger the activation of dendritic cells and enhance T cell-mediated antitumor immunity to inhibit tumor metastasis. Collectively, the nanoprobe-mediated immunogenic radiotherapy can boost the abscopal effect to inhibit tumor metastasis and prolong survival.

Analysis of using high-precision radiotherapy in the treatment of liver metastases regarding toxicity and survival

Background Hepatic metastases occur frequently in the context of many tumor entities. Patients with colorectal carcinoma have already developed liver metastases in 20% at the time of diagnosis, and 25–50% develop metastases in the further course of the disease and therapy. The frequent manifestation and the variable appearance of liver metastases result in an interdisciplinary challenge, regarding treatment management. The aim of this study was to evaluate high-precision stereotactic body radiotherapy (SBRT) for liver metastases. Methods A cohort of 115 patients with 150 irradiated liver metastases was analyzed. All metastases were treated between May 2004 and January 2020 using SBRT. A contrast-enhanced computed tomography (CT) was performed in all patients for treatment planning, followed by image-guided high-precision radiotherapy using cone-beam CT. A median cumulative dose of 35 Gy and a median single dose of 7 Gy was applied. Results Median OS was 20.4 months and median LC was 35.1 months with a 1-year probability of local failure of 18% (95%-CI: 12.0–24.3%). In this cohort, 18 patients were still alive at the time of evaluation. The median FU-time in total was 11.4 months and for living patients 26.6 months. 70.4% of patients suffered from acute toxicities. There were several cases of grade 1 and 2 toxicities, such as constipation (13.9%), nausea (24.4%), loss of appetite (7.8%), vomiting (10.4%), diarrhea (7.8%), and abdominal pain (16.5%). 10 patients (8.7%) suffered from grade 3 toxicities. Late toxicities affected 42.6% of patients, the majority of these affected the gastrointestinal system. Conclusion SBRT is becoming increasingly important in the field of radiation oncology. It has evolved to be a highly effective treatment for primary and metastasized tumors, and offers a semi-curative treatment option also in the case of oligometastatic patients. Overall, it represents a very effective and well-tolerated therapy option to treat hepatic metastases. Based on the results of this work and the studies already available, high-precision radiotherapy should be considered as a valid and promising treatment alternative in the interdisciplinary discussion.

Salvage re-irradiation using stereotactic body radiation therapy for locally recurrent prostate cancer: the impact of castration sensitivity on treatment outcomes

Background Advances in imaging, biomaterials and precision radiotherapy provide new opportunities to salvage locally recurrent prostate cancer (PC). This study evaluates the efficacy and safety of re-irradiation using stereotactic body radiation therapy (SBRT). We hypothesized that patients with castrate-resistant PC (CRPC) would benefit less from local salvage. Methods A prospective clinical database was reviewed to extract 30 consecutive patients treated with prostate re-irradiation. Gallium prostate specific membrane antigen (PSMA) ligand positron emission tomography was performed following prostate-specific antigen failure in all patients and biopsy was obtained in 18 patients (60%). Re-irradiation was either focal (n = 13) or whole-gland (n = 17). Endo-rectal balloons were used in twenty-two patients and hydrogel spacers in eight patients. The median prescription dose was 5 fractions of 6.5 (range: 6–8) Gray (Gy). Results Median follow-up was 28 months. Failure occurred in 10 (out of 11) CRPC patients versus 6 (out of 19) castrate-sensitive patients (91% vs. 32%, p = 0.008) after a median of 13 and 23 months, respectively. Metastases occurred in 64% (n = 7) of CRPC patients versus 16% (n = 3) of castrate-sensitive patients (p = 0.007). Two patients experienced local in-field recurrence, thus local control was 93%. The 2 and 3-year recurrence-free survival were 84% and 79% for castrate-sensitive patients versus 18% and 9% for CRPC patients (p < 0.001), and 3-year metastasis-free survival was 90% versus 27% (p < 0.01) for castrate-sensitive and CRPC patients, respectively. Acute grade II and III genitourinary (GU) toxicity occurred in 27% and 3%, and late GU toxicity in 30% and 3%, respectively. No ≥ grade II acute gastrointestinal (GI) toxicity occurred, and only one patient (3%) developed late grade II toxicity. Conclusions Early delivery of salvage SBRT for local recurrence is associated with excellent 3-year disease control and acceptable toxicity in the castrate-sensitive phenotype. PSMA imaging for detection of local recurrence and the use of precision radiotherapy with rectal protective devices should be further investigated as a novel salvage strategy for radio-recurrent PC.