Sinonasal Neuroendocrine Carcinoma: 15 Years of Experience at a Single Institution

Objectives Sinonasal neuroendocrine carcinomas (SNECs) are among the rarest paranasal sinus cancers. Consensus guidelines for therapy are difficult to develop due to limited data regarding the natural history and successful treatment of these tumors. This study presents 15 years of experience treating SNEC at a single institution and a review of the literature. Design Retrospective review. Setting Academic medical center in the United States. Participants Patients diagnosed with primary SNEC. Main Outcome Measures Overall survival. Results Thirteen patients were identified and included. Overall estimated survival was 74.6% at 5 years. Ten of 13 (76.9%) patients were diagnosed with high-grade neuroendocrine carcinoma and three (23.1%) with intermediate or low grade. All three patients with low- or intermediate-grade cancer survived more than 10 years from their initial diagnosis (median survival: 11.6 years) and are currently alive. The four patients who died had high-grade carcinoma, and estimated overall 5-year survival for all patients with high-grade carcinomas was 65.6%. Five patients, all with high-grade carcinoma, of seven who completed primary chemoradiation therapy (CRT) required salvage resection, and 60% are alive without disease. Conclusion This cohort has a higher overall rate of survival than many recent case series and reviews. There is consensus that multimodal therapy is preferred over monotherapy, but approaches to treatment vary widely. Our approach of surgical resection as primary therapy for low-grade tumors and primary CRT for high-grade SNEC has been successful, and could indicate hope for improved survival among these patients.

CTNI-16. TROTABRESIB (CC-90010, BMS-986378), A REVERSIBLE, POTENT ORAL BROMODOMAIN AND EXTRATERMINAL INHIBITOR (BETi) IN PATIENTS WITH HIGH-GRADE GLIOMAS: A PHASE 1 OPEN-LABEL ‘WINDOW OF OPPORTUNITY’ STUDY

Trotabresib is a potent, reversible oral BETi with antitumor activity in patients with advanced malignancies (Moreno et al. ESMO 2020. Abstract 5270). The CC-90010-GBM-001 study (NCT04047303) enrolled patients with progressive or recurrent astrocytoma or recurrent glioblastoma scheduled for salvage resection. Patients were treated with trotabresib 30 mg daily for 4 days before surgery, then trotabresib 45 mg daily 4 days on/24 days off after recovery. Primary objectives were trotabresib tumor tissue concentration and plasma pharmacokinetics (PK). Secondary and exploratory objectives included safety, antitumor activity, cerebrospinal fluid concentration, and pharmacodynamics (PD). Twenty patients were enrolled; blood PK, blood PD, and tumor PD data were available for 14, 12, and 11 patients, respectively. Geometric mean peak trotabresib plasma concentration on day 4 was 1.92 μM; median time to peak concentration was 1.5 hours. At the time of resection, geometric mean trotabresib concentrations in plasma and brain tumor tissue were 1.01 and 0.68 μM, respectively. Blood CCR1 mRNA was reduced ≥ 50% from baseline after dose 4. Blood HEXIM1 mRNA increased at 72–96 hours following first dose, and at the time of surgery the percentage increase was related to plasma trotabresib concentration. Tumor HEXIM1 RNA increased in 10 of 11 patients. Eighteen patients (90%) had ≥ 1 treatment-related adverse event (TRAE). Nine patients (45%) had grade 3/4 TRAEs, most frequently thrombocytopenia (5 patients [25%]). Only 1 patient had serious TRAEs (hemiparesis and lethargy). Two patients died of intracranial hemorrhage unrelated to study drug. Of 16 patients evaluable for antitumor response, 7 had stable disease per RANO criteria, with 3 ongoing beyond data cutoff at cycles 4–11. Median progression-free survival was 1.9 months (95% CI, 1.4–3.3). Overall, trotabresib showed good tumor tissue penetration, with PD signals of response, and was well tolerated. A study of trotabresib + temozolomide in first-line glioblastoma is ongoing (NCT04324840).

Fate of Residual Tumor After Subtotal-resected, Previously-irradiated Vestibular Schwannoma: Long-term Follow-up of a Single Institutional Series

Background: The fate of residual tumor after salvage surgery for recurrent vestibular schwannoma (VS) after radiosurgery has not been elucidated. We reviewed our surgical series of salvage surgery for recurrent VS and the natural history of the residual tumor after salvage surgery.Methods: This study enrolled 14 patients who were received salvage surgical resection in our institute and were followed-up for >12 months.Results: There were 3 male and 11 female patients with a median age of 55 years (range: 16-70). The pre-SRS tumor volume was a median 6591 mm3. All patients were treated by GKS. The median duration from GKS to surgery was 52 months (range: 10-116). Solid tumor growth was observed in 6 (42.9%) patients and cyst formation was observed in 8 patients (57.1%). Subtotal resection was performed in 13 (92.9%) patients and gross total resection was only achieved in one (7.1%) patient. Postoperative facial paresis occurred in 5 (35.7%) patients. Postoperative surgical complications occurred in 2 (14.3%) patients. After salvage resection for irradiated VS, no patient showed tumor progression or recurrence during the follow-up period (13 subtotal resection and 1 total resection). In addition, 2 patients in the subtotal resection group showed residual tumor shrinkage after salvage surgery during the follow-up periodConclusion: The behavior of residual tumors after salvage surgery for irradiated VS was stable. Adjuvant treatment for these residual tumors may not be necessary.

Outcomes of Salvage Resection and Radiosurgery Following Failed Primary Treatment of Vestibular Schwannomas

Objective To evaluate outcomes following salvage microsurgery (MS) and salvage stereotactic radiosurgery (SRS) after failure of primary treatment for vestibular schwannomas (VS). Study Design Retrospective chart review. Setting Tertiary referral center. Methods Patients with more than 1 intervention for their VS were divided into 4 groups: MS followed by SRS (n = 61), MS followed by MS (n = 9), SRS followed by MS (n = 7), and SRS followed by SRS (n = 7), and outcomes were evaluated. Results A total of 77 patients were included (84 procedures). In group 1 (MS then SRS), 3% developed a decline in facial function, 3% developed trigeminal sensory loss, and 13% patients had gradual improvement of facial nerve function following SRS. Group 2 (MS then MS) had the highest rates of facial nerve deterioration, although all but 1 patient achieved a House-Brackmann score of II or III. Gross-total resection (GTR) was achieved in 56% of patients. When a different approach was used for salvage resection, GTR occurred more commonly, and facial nerve outcomes were similar. In group 3 (SRS then MS), GTR occurred in 43% of cases, and 2 of 7 patients developed worsened facial function. In group 4 (SRS then SRS), no patient developed facial weakness after reirradiation, and 1 developed a trigeminal nerve deficit. Conclusions For MS recurrences/residuals, SRS is the mainstay of treatment and does not preclude facial function recovery. If salvage microsurgery is required, an alternate approach should be considered. For SRS failures, when MS is required, less-than GTR may be preferable, and reirradiation is a potential safe alternative.

Fate of residual tumor after subtotal-resected, previously-irradiated vestibular schwannoma: Long-term follow-up of a single institutional series

Background The fate of residual tumor after salvage surgery for recurrent vestibular schwannoma (VS) after radiosurgery has not been elucidated. We reviewed our surgical series of salvage surgery for recurrent VS and the natural history of the residual tumor after salvage surgery. Methods This study enrolled 14 patients who were received salvage surgical resection in our institute and were followed-up for > 12 months. Results There were 3 male and 11 female patients with a median age of 55 years (range: 16–70). The pre-SRS tumor volume was a median 6591 mm3. All patients were treated by GKS. The median duration from GKS to surgery was 52 months (range: 10–116). Solid tumor growth was observed in 6 (42.9%) patients and cyst formation was observed in 8 patients (57.1%). Subtotal resection was performed in 13 (92.9%) patients and gross total resection was only achieved in one (7.1%) patient. Postoperative facial paresis occurred in 5 (35.7%) patients. Postoperative surgical complications occurred in 2 (14.3%) patients. After salvage resection for irradiated VS, no patient showed tumor progression or recurrence during the follow-up period (13 subtotal resection and 1 total resection). In addition, 2 patients in the subtotal resection group showed residual tumor shrinkage after salvage surgery during the follow-up period Conclusion The behavior of residual tumors after salvage surgery for irradiated VS was stable. Adjuvant treatment for these residual tumors may not be necessary.

MLTI-05. Adjuvant re-irradiation improves local control of surgically resected recurrent brain metastases

Background The efficacy of salvage resection (SR) of recurrent brain metastases (BrM) post-stereotactic radiosurgery (SRS) is not well described. We sought to characterize the impact of adjuvant post-salvage radiation therapy (PSRT) in this setting and identify tumor-specific variables that influence local control. Methods Retrospective analysis of post-SRS recurrent BrM that underwent SR between 2003–2020 at Memorial Sloan Kettering Cancer Center was performed. Cases with histologically-viable malignancy were included and stratified by receipt of adjuvant PSRT within 60 days of SR (PSRT cohort) vs. observation (observation cohort). Resection-site outcomes were described using cumulative incidences and univariate and multivariate competing risks regression accounting for clustering. Results One-hundred fifty-five recurrent BrM in 135 patients were included. Thirty-nine (25.2%) of the post-operative cavities were treated with adjuvant PSRT, and the remaining 116 (74.8%) cavities were initially observed. Gross- or near-total resection was associated with significantly improved local control compared to subtotal resection (p=0.007). Adjuvant PSRT was associated with a reduced rate of LR at 6 months [18.0% (95%CI: 9.8–33.1%) vs. 35.9% (95%CI: 27.9–46.2%) with initial observation] and 12 months [28.8% (95%CI: 17.0–48.8%) vs. 43.9% (95%CI: 36.2–53.4%)]. On multivariate analysis, adjuvant PSRT (p=0.095), low tumor-viability within the resected BrM (p=0.17), and first-time resection (p=0.035) all independently trended towards improved local control. BrM size at SR (≥3cm vs. <3cm, p=0.48), primary malignancy (p=0.35), and specific PSRT modality (whole or partial brain radiation vs. SRS, p=0.43) were not associated with differences in LR rate. Radiation necrosis (RN) was significantly increased in the PSRT cohort (HR 4.55, 95%CI: 1.26–16.39, p=0.02), though the total percentage with symptomatic RN remained low (PSRT cohort 5.1% vs observation cohort 0.9%). Conclusions Local control after SR of a recurrent BrM may be optimized with gross- or near-total resection and adjuvant post-operative re-irradiation, with low symptomatic RN.

Recurrence of Gastric Cancer in the Jejunum Close to the Anastomotic Site after Total Gastrectomy

A 61-year-old man underwent total gastrectomy with esophago-jejunostomy for Borrmann type I gastric cancer. Postoperative intra-abdominal abscess made the patient unable to receive adjuvant chemotherapy. Only 23 weeks after operation, the patient developed melena and anemia, leading to the diagnosis of recurrence in the jejunum close to the anastomotic site. The patient received salvage resection of the recurrence. Pathological study showed that the tumor was composed of atypical cells similar to those of the primary gastric cancer. Normal jejunal mucosa was observed between the esophagus and the recurrent tumor. We judged that exfoliation of the gastric cancer cells caused the recurrence due to both the very short disease-free interval and pathological findings. Surgeons should pay attention to this type of recurrence especially for Borrmann type I gastric cancer. In addition to the adjuvant chemotherapy, gastric irrigation using distilled water during the operation seems to be a feasible measure to prevent this type of recurrence.

Case Report: Transarterial Chemoembolization in Combination With Tislelizumab Downstages Unresectable Hepatocellular Carcinoma Followed by Radical Salvage Resection

IntroductionTransarterial chemoembolization (TACE) is inefficient at converting unresectable hepatocellular carcinoma (uHCC) to resectable. Treatment with immune checkpoint inhibitors (ICIs) is an emerging strategy for uHCC. Combined therapy of TACE with ICIs is considered to improve the therapeutic effect.Case presentationA 45-year-old man was diagnosed with a bulky HCC under cirrhotic background without distant metastasis. Curative resection was infeasible, and TACE plus tislelizumab (an ICI targeting PD-1) was applied. The treatment course, starting from TACE and followed by tislelizumab one week later, was repeated every four weeks. After three courses, the tumor showed striking shrink in volume with complete radiological response, which permitted salvage resection. Notably, pathological examination found complete necrosis of the tumor with massive infiltration of lymphocytes in the tumor-nontumor interface and extensive granulomatous inflammation in the surrounding nontumor liver, indicating activated immune response synergistically caused by TACE with tislelizumab. The patient is now living well without tumor recurrence for 6 months after surgery.ConclusionTACE in combination with tislelizumab may represent a potent strategy for uHCC. Data from randomized clinical trials are needed to assess its safety and effect in the setting of preoperative downstaging therapy.