Surgical peri-implantitis treatment with and without guided bone regeneration. A randomized controlled trial

Objective: To evaluate the efficacy of reconstructive peri-implantitis treatment. Materials and Methods: Forty participants, with peri-implantitis and a contained intraosseous defect, were randomized to access flap (control) or access flap with xenograft and collagen membrane (test). All received systemic antimicrobials. Blinded examiners recorded probing depths (PD), bleeding and suppuration on probing (BOP & SOP), soft tissue levels, and marginal bone levels (MBL) at baseline and 12 months. Patient reported outcomes were recorded. The primary outcome was PD change. Results: All 40 participants (40 implants) completed the 12-month study. The mean (standard deviation) PD reduction (deepest site) was 4.2 (1.8) mm in the control and 3.7 (1.9) mm in the test group. MBL gain (deepest site) was 1.7 (1.6) mm in the control and 2.4 (1.4) mm in the test group. Absence of BOP & SOP was observed at 60% of both control and test implants. Buccal recession was 0.9 (1.6) mm in the control and 0.4 (1.1) mm in the test group. A successful outcome (absence of PD ≥ 5 mm with BOP, absence of SOP and absence of progressive bone loss) was achieved for 90% of the control and 85% of test group implants. No statistically significant differences in clinical or radiographic parameters were found between treatment groups. 30% of participants experienced mild gastro-intestinal disturbances. Reporting followed CONSORT guidelines. Conclusion: Similar clinical and radiographic improvements at 12 months were observed with high levels of patient satisfaction for both the access flap and xenograft covered by collagen membrane groups. Registered clinical trials.gov. ID:NCT03163602 (23/05/2017)

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Surgical peri-implantitis treatment with and without guided bone regeneration. A randomized controlled trial

Objective To evaluate the efficacy of reconstructive peri-implantitis treatment. Materials and Methods Forty participants, with peri-implantitis and a contained intraosseous defect, were randomized to access flap (control) or access flap with xenograft and collagen membrane (test). All received systemic antimicrobials. Blinded examiners recorded probing depths (PD), bleeding and suppuration on probing (BOP & SOP), soft tissue levels, and marginal bone levels (MBL) at baseline and 12 months. Patient reported outcomes were recorded. The primary outcome was PD change. Results All 40 participants (40 implants) completed the 12-month study. The mean (standard deviation) PD reduction (deepest site) was 4.2 (1.8) mm in the control and 3.7 (1.9) mm in the test group. MBL gain (deepest site) was 1.7 (1.6) mm in the control and 2.4 (1.4) mm in the test group. Absence of BOP & SOP was observed at 60% of both control and test implants. Buccal recession was 0.9 (1.6) mm in the control and 0.4 (1.1) mm in the test group. A successful outcome (absence of PD ≥ 5 mm with BOP, absence of SOP and absence of progressive bone loss) was achieved for 90% of the control and 85% of test group implants. No statistically significant differences in clinical or radiographic parameters were found between treatment groups. 30% of participants experienced mild gastro-intestinal disturbances. Reporting followed CONSORT guidelines. Conclusion Similar clinical and radiographic improvements at 12 months were observed with high levels of patient satisfaction for both the access flap and xenograft covered by collagen membrane groups

Ablative 5-Fraction Stereotactic Magnetic Resonance–Guided Radiation Therapy With On-Table Adaptive Replanning and Elective Nodal Irradiation for Inoperable Pancreas Cancer

Purpose: Radiotherapy (RT) dose escalation using stereotactic body radiation therapy (SBRT) may significantly improve both local control (LC) and overall survival (OS) for patients with inoperable pancreas cancer. However, ablative dose cannot be routinely offered because of the risk of causing severe injury to adjacent normal organs. Stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) represents a novel technique that may achieve safe delivery of ablative dose and improve long-term outcomes. Methods and materials: We performed a single institution retrospective analysis of 35 consecutive pancreatic cancer patients treated with SMART in mid-inspiration breath hold on an MR-LINAC. Most had locally advanced disease (80%) and received induction chemotherapy (91.4%) for a median 3.9 months prior to SBRT. All were prescribed 5 fractions delivered in consecutive days to a median total dose of 50 Gy (BED10 100 Gy10), typically with a 120-130% hotspot. Elective nodal irradiation was delivered to 20 (57.1%) patients. No patient had fiducial markers placed and all were treated with continuous intrafraction MR visualization and automatic beam triggering. Results: With median follow-up of 10.3 months from SMART, acute (2.9%) and late (2.9%) grade 3 toxicities were uncommon. One-year LC, distant metastasis-free survival, progression-free survival, cause-specific survival, and OS were 87.8%, 63.1%, 52.4%, 77.6% and 58.9%, respectively. Conclusions: To our knowledge, this is the first report of 5-fraction pancreas SMART delivered on an MR-LINAC. We observed minimal severe treatment-related toxicity and encouraging early LC. Prospective confirmation of feasibility and long-term clinical outcomes of dose intensified SMART is warranted

Outcomes and Toxicities of Modern Combined Modality Therapy with Atezolizumab Plus Bevacizumab and Radiation Therapy for Hepatocellular Carcinoma

Atezolizumab plus bevacizumab has become frontline therapy for unresectable HCC. The compatibility of atezolizumab/bevacizumab with liver-directed RT has not been reported. Methods: HCC patients treated with liver-directed RT and atezolizumab/bevacizumab between 1/2020&ndash;11/2021 were included. Toxicity and outcomes were retrospectively recorded. For ALCs, we matched the analysis to a previously cohort of RT-treated HCC patients who did not receive atezolizumab/bevacizumab. Survival and time-to-liver-failure were analyzed using Kaplan&ndash;Meier. Results: Of 21 patients, with a median follow-up of 9.5 months, the median OS was 16.1 months. Post-RT, all patients had reduced tumors or treatment response. There were no &ge;Grade 3 RT-related toxicities. Autoimmune complications occurred in two patients (9.5%), and GI bleeding in three patients (14.3%). Liver function remained stable post-RT. There was a marked decrease in ALCs immediately post-RT (post-RT/pre-RT ratio 47.3%, p &lt; 0.0001), restored by 1 month to pre-treatment baseline (1-month post-RT/pre-RT ratio 95.1%, n.s.). Compared to HCC patients treated with RT alone, post-RT ALC recovery was faster with atezolizumab/bevacizumab (p = 0.009). Conclusion: In this first reported experience of RT with modern systemic therapy for HCC, combination therapy is safe and well-tolerated. As a favorable prognosticator, there appears to be faster recovery of ALC among patients who received RT with atezolizumab/bevacizumab

Outcomes and Toxicities of Modern Combined Modality Therapy with Atezolizumab Plus Bevacizumab and Radiation Therapy for Hepatocellular Carcinoma

Atezolizumab plus bevacizumab has become frontline therapy for unresectable HCC. The compatibility of atezolizumab/bevacizumab with liver-directed RT has not been reported. Methods: HCC patients treated with liver-directed RT and atezolizumab/bevacizumab between 1/2020–11/2021 were included. Toxicity and outcomes were retrospectively recorded. For ALCs, we matched the analysis to a previously cohort of RT-treated HCC patients who did not receive atezolizumab/bevacizumab. Survival and time-to-liver-failure were analyzed using Kaplan–Meier. Results: Of 21 patients, with a median follow-up of 9.5 months, the median OS was 16.1 months. Post-RT, all patients had reduced tumors or treatment response. There were no ≥Grade 3 RT-related toxicities. Autoimmune complications occurred in two patients (9.5%), and GI bleeding in three patients (14.3%). Liver function remained stable post-RT. There was a marked decrease in ALCs immediately post-RT (post-RT/pre-RT ratio 47.3%, p p = 0.009). Conclusion: In this first reported experience of RT with modern systemic therapy for HCC, combination therapy is safe and well-tolerated. As a favorable prognosticator, there appears to be faster recovery of ALC among patients who received RT with atezolizumab/bevacizumab

Definitive liver radiotherapy for intrahepatic cholangiocarcinoma with extrahepatic metastases

Introduction: Tumor-related liver failure (TRLF) is the most common cause of death in patients with intrahepatic cholangiocarcinoma (ICC). Though we previously showed that liver radiotherapy (L-RT) for locally advanced ICC is associated with less frequent TRLF and longer overall survival (OS), the role of L-RT for patients with extrahepatic metastatic disease (M1) remains undefined. We sought to compare outcomes for M1 ICC patients treated with and without L-RT. Methods: We reviewed ICC patients found to have M1 disease at initial diagnosis at a single institution between 2010 and 2021 who received L-RT, matching them with an institutional cohort by propensity score and a National Cancer Database (NCDB) cohort by frequency technique. The median biologically effective dose (BED10) was 98 Gy (interquartile range [IQR] 80.5-97.9 Gy) for L-RT. Patients treated with other local therapies or supportive care alone were excluded. We analyzed survival with Cox proportional hazards modeling. Results: We identified 61 patients who received L-RT and 220 who received chemotherapy alone. At median follow up of 11 months after diagnosis, median OS was 9 months (95% confidence interval [CI] 8-11) and 21 months (CI 17-26) for patients receiving chemotherapy alone and L-RT, respectively. TRLF was the cause of death more often in the patients who received chemotherapy alone compared to those who received L-RT (82% vs. 47%; P=0.001). On multivariable propensity-score matched analysis, associations with lower risk of death included duration of upfront chemotherapy (hazard ratio [HR] 0.82; P=0.005) and receipt of L-RT (HR 0.40; P=0.002). The median OS from diagnosis for NCDB chemotherapy alone cohort was shorter than that of the institutional L-RT cohort (9 vs. 22 months; P<0.001). Discussion/Conclusion: For M1 ICC, L-RT associated with a lower rate of death due to TRLF and longer OS vs. those treated with chemotherapy alone. Prospective studies of L-RT in this setting are warranted