No abstract

Advanced hepatocellular carcinoma has limited treatment options, but there has been extensive growth recently with cabozantinib, regorafenib, lenvatinib, nivolumab, atezolizumab, and bevacizumab, which are some of the treatments that have received FDA approval just over the last three years. Because HCC tumor microenvironment is potentially immunogenic and typically characterized by inflammation, immunotherapy has been proposed as a potential novel therapeutic approach, which has prompted studies in advanced HCC patients investigating various immune-therapeutic strategies such as CAR-T cell therapy, checkpoint inhibitors, and onco-vaccines. The anti-PD-1 checkpoint inhibitors nivolumab and pembrolizumab have been FDA approved as a second line treatment in patients who progressed or are intolerant to Sorafenib. To build up on the success of PD-1 monotherapy, combinatorial regimens with PD-1/PD-L1 inhibitors plus VEGF targeted agents have shown positive results in various malignancies including HCC. The combination of atezolizumab plus bevacizumab is the new addition to the HCC treatment armamentarium following a pivotal study that demonstrated an improvement in OS over frontline sorafenib. Other novel immune-based approaches and oncolytic viruses are in the early phases of clinical evaluation. These innovative approaches enhance the intensity of cancer-directed immune responses and will potentially impact the outlook of this aggressive disease.

Introduction. Ampullary cancers represent a subset of periampullary cancers, comprising only 0.2% all gastrointestinal cancers. Localized disease is primarily managed by a surgical intervention, called pancreaticoduodenectomy (PD), followed in many cases by the administration of adjuvant chemotherapy (CT) or chemoradiation therapy (CRT). However, there are no clear evidence-based guidelines to aid in selecting both the modality and regimen of adjuvant therapy for resected Ampullary carcinoma. Methods. We retrospectively analyzed 54 patients at KU Cancer Center, who had undergone endoscopic resection or pancreaticoduodenectomy (PD) for Ampullary cancer from June 2006 to July 2016. We obtained patients’ baseline characteristics, clinical presentation, pathology, treatment modality, recurrence pattern, and survival outcomes. The time-to-events data were compared using Kaplan-Meier methods. A univariate and multivariate Cox proportional hazards regression was performed to evaluate factors associated with overall survival (OS) and generate hazard ratios (HR). Results. The mean age of the 54 patients was 68 (37-90). 38 (70%) were males and 16 (30%) were females. Most of the patients were Caucasian (76%). Approximately half of all patients had a history of smoking, 20% had alcohol abuse, and 13% had pancreatitis. Among the 54 patients with localized cancers, 9 (16%) were treated definitively with nonoperative therapies, usually due to a prohibitive comorbidity profile, performance status, or unresectable tumor. 45 out of 54 patients (83%) underwent surgery. Of the 45 patients who underwent surgery, 18 patients (40% of the study cohort) received adjuvant therapy due to concerns for advanced disease as determined by the treating physician. 13 patients (24%) received adjuvant CT and 5 patients (9.2%) received CRT. The remaining 27 patients (50%) underwent surgery alone. The median OS for the entire study cohort was 30 months. When compared to surgery alone, adjuvant therapy with either CT or CRT had no statistically significant difference in terms of progression-free survival (p=0.56) or overall survival (p=0.80). In univariate Cox proportional hazards regression analysis, high-risk features like peripancreatic extension (16%) and perineural invasion (26%) were found to be associated with poor OS. Lymph node metastasis (29%) did not significantly affect OS (HR 1.42, 95% CI [0.73-1.86]; p=0.84). Lymphovascular invasion (29%) was not associated with poor OS (HR 1.22, 95% CI [0.52, 2.96]; p=0.76). In multivariate Cox regression analysis, only age group>70 years was significantly associated with OS , while other factors, including the receipt of adjuvant therapy, lymph nodes, positive margin, and lymphovascular, perineural, and peripancreatic involvement, were not significantly associated with OS. These results are likely due to small sample size. Conclusions. Despite numerous advances in both cancer care and research, efforts in rare malignancies such as Ampullary cancer remain very challenging with a clear lack of an evidence-based standard of care treatment paradigm. Although adding adjuvant therapies such as chemotherapy or chemoradiotherapy is likely to improve survival in high-risk disease, there is no standardized regimen for the treatment of Ampullary cancer. More research is required to elucidate whether statistically and clinically relevant differences exist that may warrant a change in the current adjuvant treatment strategies.

No abstract

This retrospective study sought to report our institutional experience in stereotactic ablative radiotherapy (SABR) for adrenal gland metastases in lung cancer and the impact of histology subtype and molecular profile on clinical outcomes. Materials/Methods: Data were retrieved from lung cancer patients with controlled disease under systemic therapy received SABR to adrenal gland metastases between 2012 to 2018 in a single medical center. Tumor response was evaluated by revised Response Evaluation Criteria in Solid Tumors guideline using computed tomography scans. Local failure was designated as recurrence within the irradiated field. Progressive disease or new lesions outside the treated adrenal tumor(s) was defined as distant failure. Overall survival (OS), progression-free survival (PFS), time to local failure (tLF) and time to distant failure (tDF) were estimated using Kaplan-Meier method from the date of SABR delivery. Cox proportional hazards method was used for evaluation of prognostic factors. Results: In total, 29 patients were enrolled for analysis, and 23 had oligometastatic disease. SABR was delivered with a median dose of 50 Gy (range 36-50 Gy) in 4-6 fractions (median, 6 fractions). Twenty-three patients had non-small cell lung cancer (adenocarcinoma 18, squamous cell carcinoma 3), and 6 had small cell lung cancer. The median planning target volume (PTV) was 79 cc, and the median biological equivalence dose (BED) was 66.7 Gy (range 57.6-105.6 Gy). There were 3 complete response (CR, 9%), 19 partial response (PR, 59%), 7 stable disease (SD, 23%), and 3 progressive disease (9%). The overall objective radiographic response (ORR, CR+PR) rate and disease control (CR+PR+SD) rate were 78% and 91%, respectively. With a median follow-up of 9.5 months, the median OS, PFS, and tDF were 9.5 months, 4.2 months, and 4.3 months, respectively. The median tLF was not reached. In univariate analysis, ORR was associated with an improved OS (pZ0.04), PFS (pZ0.008), tLF (pZ0.006), and tDF (pZ0.02), while oligo-metastatic status was a favorable prognosticator of OS (pZ0.046), PFS (pZ0.008) and tDF (pZ0.003). Lung cancer histology was not associated with ORR, OS, PFS, tLF, or tDF. The significance of both ORR and oligo-metastatic status remained in multivariate analyses. In the subgroup of NSCLC adenocarcinoma, 45% had mutant epidermal growth factor receptor (EGFR). There were no significant differences in ORR or survival outcomes between patients with wild type EGFR and those with mutant EGFR. No patients experienced grade 3 to 5 toxicities. Conclusion: SABR to adrenal metastases is well-tolerated and provides excellent local control in lung cancer patients. Histology subtype or EGFR mutation status has no impact on clinical outcomes. Patients with radiographic response or oligometastatic disease had favorable survivals.